The basal ganglia are deep nuclei in the brain that include the caudate, putamen, globus pallidus, and substantia nigra. Pathological processes involving the basal ganglia often result in disorders of movement and behavior. A number of different autoimmune disorders predominantly involve the basal ganglia and can result in movement and psychiatric disorders. The classic basal ganglia autoimmune disorder is Sydenham chorea, a poststreptococcal neuropsychiatric disorder. Resurgence in the interest in Sydenham chorea is the result of the descriptions of other poststreptococcal neuropsychiatric disorders including tics and obsessive-compulsive disorder, broadly termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Encephalitic processes affecting the basal ganglia are also described including the syndromes basal ganglia encephalitis, encephalitis lethargica, and bilateral striatal necrosis. Last, systemic autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome can result in chorea or parkinsonism. Using paradigms learned from other autoantibody associated disorders, the authors discuss the autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders. Identification of these entities is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system. PMID:22832771
Dale, Russell C; Brilot, Fabienne
Purpose of Review. Studies have been published in the field of autoimmune thyroid diseases since January 2005. The review is organized into areas of etiology, autoimmune features, autoantibodies, mechanism of thyroid cell injury, B-cell responses, and T-cell responses. Also it reviews the diagnosis and the relationship between autoimmune thyroid disease, neoplasm, and kidney disorders. Recent Findings. Autoimmune thyroid diseases have been reported in people living in different parts of the world including North America, Europe, Baalkans, Asia, Middle East, South America, and Africa though the reported figures do not fully reflect the number of people infected per year. Cases are unrecognized due to inaccurate diagnosis and hence are treated as other diseases. However, the most recent studies have shown that the human autoimmune thyroid diseases (AITDs) affect up to 5% of the general population and are seen mostly in women between 30 and 50 years. Summary. Autoimmune thyroid disease is the result of a complex interaction between genetic and environmental factors. Overall, this review has expanded our understanding of the mechanism involved in pathogenesis of AITD and the relationship between autoimmune thyroid disease, neoplasm, and kidney disease. It has opened new lines of investigations that will ultimately result in a better clinical practice.
Iddah, M. A.; Macharia, B. N.
Several monoclonal antibodies and other biologic drugs are used to treat a variety of common autoimmune disorders that are progressive in nature or resistant to standard therapies. Although monoclonal antibodies were recently removed from the hazardous drugs list, most of these drugs are considered high-risk substances that require specialized knowledge regarding care before, during, and after administration. Yet no national standards exist for nurses working with autoimmune patients, nor have minimum nursing practice competency guidelines been identified. Expert practitioners must continue to educate other health care professionals about the drugs, their intended and off-label uses, their potential side effects, and proactive measures that need to be taken to ensure patient safety during the entire drug administration process. PMID:24583941
The many features that link autoimmune disorders (AD) and lymphoma are reviewed herein. Firstly, the epidemiology indicates the increased risk of non-Hodgkin's lymphoma (NHL) development in many AD, and especially in Sjögren's syndrome, rheumatoid arthritis and systemic lupus erythematosus. In these AD, the relative risk of NHL occurrence varies between 2 and 4 up to 40 fold higher than in the general population, according to various surveys. Factors favouring or predicting NHL have been reported in detail. B-cell activation and proliferation are part of AD and are essential factors for the onset of malignant cell clones in a deregulated immunological environment. Targeting deregulated or malignant B-cells is the goal of some newly developed treatments. The prototype is anti-CD20 rituximab that has substantially modified the prognosis of B-cell NHL and is also an effective new treatment opportunity for some AD. Similarly, intensified treatments with autologous haematopoietic stem cell transplant (ASCT) that were developed for high-risk lymphoma are now under advanced investigation for use in some refractory AD. Thus, the successful use of rituximab and ASCT in both AD and NHL further emphasizes the close link between these two entities. This review provides details on the main epidemiological features regarding NHL incidence in AD, the pathogenetic factors that favour lymphoma onset and some recent advances in therapeutic approaches that are effective in both autoimmune and malignant lymphoproliferative disorders. PMID:23219771
Tarella, C; Gueli, A; Ruella, M; Cignetti, A
Autoimmune bullous skin diseases, such as pemphigus vulgaris (PV) and bullous pemphigoid (BP), are severe, frequently life-threatening skin disorders. Immunologically, they are characterized by the presence of serum autoantibodies (auto-Ab) targeting distinct adhesion molecules of the epidermis or dermoepidermal basement membrane zone. Antibody (Ab) binding interferes with the adhesive function of these molecules, leading to detachment and subsequently blister formation.
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) is a group of disorders recently recognized as a clinical entity. A case of PANDAS is described here, which remitted after 1 month of treatment. Recent Group A beta-hemolytic streptococcus infection should be considered in a child who presents with a sudden explosive onset of tics or obsessive compulsive symptoms.
Maini, Baljeet; Bathla, Manish; Dhanjal, Gurdeep S.; Sharma, Prem D.
Abnormal autoimmune activity has been implicated in a number of neuropsychiatric disorders. In this review, the authors discuss a newly recognized class of synaptic autoimmune encephalitides as well as behavioral and cognitive manifestations of systemic autoimmune diseases.
Kayser, Matthew S.; Dalmau, Josep
Systemic autoimmune disorders affect multiple organ systems. Brain involvement commonly causes seizures, which may be the presenting symptom. Systemic lupus erythematosus, Sjorgren's syndrome, Wegener's granulomatosis, sarcoidsosis, celiac disease, Crohn's disease, Behcet's, and Hashimoto's encephalopathy are reviewed. Mechanisms underlying CNS pathology in systemic autoimmune disorders-and specifically factors predisposing these patients-are discussed, including vascular disease (e.g., prothrombotic state, anticardiolipin antibody, emboli, vasculitis), antineuronal antibodies, immune complexes, cytokines, metabolic disorders, infection, and therapy. Diagnostic and therapeutic strategies must be individualized for both the disorder and the patient. Systemic autoimmune disorders affect multiple organ systems and frequently involve the central and peripheral nervous systems. Seizures are among the most common neurological manifestation and occasionally can be the presenting symptom. There are many causes of seizures in systemic autoimmune disorders (Table 1), and the first clinical challenge is to determine not only the cause but also the significance of seizures. In some cases, they are clues to metabolic or infectious disorders or medication toxicity; in other cases, seizures herald a life-threatening progression of the underlying illness. PMID:23646005
Devinsky, Orrin; Schein, Adam; Najjar, Souhel
Systemic autoimmune disorders affect multiple organ systems. Brain involvement commonly causes seizures, which may be the presenting symptom. Systemic lupus erythematosus, Sjorgren's syndrome, Wegener's granulomatosis, sarcoidsosis, celiac disease, Crohn's disease, Behcet's, and Hashimoto's encephalopathy are reviewed. Mechanisms underlying CNS pathology in systemic autoimmune disorders—and specifically factors predisposing these patients—are discussed, including vascular disease (e.g., prothrombotic state, anticardiolipin antibody, emboli, vasculitis), antineuronal antibodies, immune complexes, cytokines, metabolic disorders, infection, and therapy. Diagnostic and therapeutic strategies must be individualized for both the disorder and the patient. Systemic autoimmune disorders affect multiple organ systems and frequently involve the central and peripheral nervous systems. Seizures are among the most common neurological manifestation and occasionally can be the presenting symptom. There are many causes of seizures in systemic autoimmune disorders (Table 1), and the first clinical challenge is to determine not only the cause but also the significance of seizures. In some cases, they are clues to metabolic or infectious disorders or medication toxicity; in other cases, seizures herald a life-threatening progression of the underlying illness.
Devinsky, Orrin; Schein, Adam; Najjar, Souhel
Vitamin D levels depend on many variables, including sun exposure, age, ethnicity, body mass index, use of medications and supplements. A much higher oral vitamin D intake than the current guidelines is necessary to maintain adequate circulating 25(OH)D levels in the absence of UVB radiation of the skin. In addition to the traditional known metabolic activities, vitamin D has been shown to modulate the immune system, and its deficiency has been linked to the development of several autoimmune disorders including type 1 diabetes and multiple sclerosis. Experimental use of vitamin D has revealed a novel role in the immunopathogenesis of autoimmune diseases. Disorders such as systemic lupus erythematosus, rheumatoid arthritis, Behçet's, polymyositis/dermatomyositis and systemic scleroderma have all been associated to some extent to vitamin D deficiency. If vitamin D deficiency occurs at a higher rate in patients with autoimmune disorders, then appropriate supplementation may be indicated. PMID:20146942
Pelajo, Christina F; Lopez-Benitez, Jorge M; Miller, Laurie C
A few studies have shown a high prevalence of thyroid autoimmunity in patients with psoriatic arthritis. However, thyroid autoimmunity has not been investigated in patients with psoriasis who do not have psoriatic arthritis. We aimed to investigate thyroid autoimmunity in patients with psoriasis. The study included 105 consecutive patients with psoriasis who did not have psoriatic arthritis and a sex and age matching control group consisting of 96 patients with tinea pedis. All of the patients with psoriasis were examined dermatologically and PASI scores were calculated for each patient. Free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), antithyroglobulin (AbTG), and antithyroidperoxidase antibody (AbTPO) levels were measured in all of the subjects. The levels of TSH, FT3, FT4, AbTG and AbTPO and ultrasonographic findings of thyroid gland were compared statistically between psoriasis and control groups. Also, the levels of TSH, FT3, FT4, AbTG and AbTPO of psoriasis patients were compared with PASI scores. Mann-Whitney U test was used as statistical method. The mean age of patients with psoriasis was 40.54 +/- 16.91 years. 56 patients were female, 49 were male. The levels FT4 were found to be significantly increased in the patient group. But levels of AbTPO and AbTG were not statistically different between the two groups. The patients who had thyroiditis plus nodules in thyroid ultrasonography had statistically longer disease periods. This is the first study that investigated autoimmune thyroid disorders in patients with psoriasis who did not have arthritis. We believed that thyroid autoimmunity in patients with psoriasis was no different from that found in healthy individuals. PMID:19251564
Gul, Ulker; Gonul, Müzeyyen; Kaya, Ilhan; Aslan, Erkan
Autoimmune polyglandular syndrome (APS) is a disorder which is associated with multiple endocrine gland insufficiency and also with non-endocrine manifestations. The pathophysiology of APS is poorly understood, but the hallmark evidence of APS is development of autoantibodies against multiple endocrine and non-endocrine organs. These autoantibodies are responsible for the dysfunction of the affected organs and sometimes may also cause non-endocrine organ dysfunction. The hemolytic-uremic syndrome (HUS) is a serious and life-threatening disease which develops due to many etiological factors including autoimmune disorders. Here, we present an unusual case of APS. Ectodermal dysplasia with immune deficiency and HUS occurred concomitantly in the same patient with APS type 3c. Once the autoantibody generation was initiated in the human body, development of multiple disorders due to organ dysfunction and also autoantibody-related diseases may have occurred.
Buyukcelik, Mithat; Keskin, Mehmet; Keskin, Ozlem; Bay, Ali; Demircioglu K?l?c, Beltinge; Kor, Y?lmaz; K?l?nc, M. Arda; Balat, Ayse
microRNAs, short ribonucleic acid molecules which is typically 20-25 nucleotides long, can bind to complementary sequences in the three prime untranslated regions of target mRNAs, leading to the inhibition of translation or degradation of the mRNA. Theologically, human genome may have more than 1000 microRNAs, which target about 60% of human mRNAs. Thus, microRNAs have been implicated in the pathogenesis of various disorders. This paper discusses the present day understanding about the expression and role in various autoimmune diseases including rheumatoid arthritis, Sjogren syndrome, polymyositis/dermatomyositis, systemic lupus erythematosus, scleroderma, type I diabetis, and psoriasis. For example, the expression of miR-29, which targets type I collagen mRNA, is reported to be down-regulated in cultured dermal fibroblasts derived from scleroderma skin, contributing to excessive collagen production in this disease. Supplementation of the microRNA results in the decrease of collagen expression in scleroderma fibroblasts. In addition, serum miR-29a levels are significantly decreased in the very early stage of scleroderma. Investigation of the involvement of microRNAs in the pathogenesis of each autoimmune disease may lead to develop new biomarker and new therapeutic approach. PMID:22214804
A 10-year-old boy with acute onset cranial diabetes insipidus and multiple autoimmune disorders had evolving panhypopituitarism, thought to be due to autoimmune hypophysitis. Over 18 months, a dramatic clinical course with progressive hypopituitarism and development of type 1 diabetes mellitus was evident. Serial brain imaging showed changes suggestive of germinoma. PMID:23586429
Jevalikar, Ganesh; Wong, Sze Choong; Zacharin, Margaret
Autoimmune diseases can be preceded by a symptom-free phase which is defined by the presence of autoantibodies, and may last\\u000a for many years. These autoantibodies may have a high positive predictive value for disease onset, severity and organ-specific\\u000a complications, especially in genetically prone individuals. Characteristic autoantibodies and susceptible genes have been\\u000a identified in many autoimmune systemic and mucocutaneous diseases such
Agmon-Levin Nancy; Shoenfeld Yehuda
Prolactin is a hormone with a multidirectional proinflammatory action. It has an anti-apoptotic effect, enhances proliferative response to antigens and mitogens, as well as enhances the production of immunoglobulins and autoantibodies. Increased prolactin levels are commonly observed in various organ and multi-organ specific autoimmune diseases. In our article, we report a case of a woman who developed progression of autoimmune thyroid disorder and developed insufficiency of the zona glomerulosa when her prolactin levels were increased. A normalization of plasma prolactin levels by quinagolide and replacement of risperidone with aripiprazole improved her clinical condition. Our study suggests that, in some patients, hyperprolactinemia may predispose to the development and progression of autoimmune disorders of endocrine glands. PMID:22635088
Krysiak, Robert; K?dzia, Agnieszka; Okopie?, Bogus?aw
T helper 17 (Th17) cells are characterized by the secretion of IL-17, a proinflammatory cytokine. They represent a newly described T helper subpopulation that is distinct from Th1 and Th2 lineages. Because of their pleiotropic activity on fibroblasts, keratinocytes, endothelial cells, neutrophils and memory T cells, Th17 cells are thought to be crucial in mediating tissue inflammation and autoimmunity. Autoimmune diseases were classically considered as Th1-mediated disorders such as rheumatoid arthritis or mixed Th1/Th2 diseases such as inflammatory bowel diseases, systemic lupus erythematosus, bullous diseases, but new evidence suggests the deep involvement of Th17 cells in their pathogenesis that, potentially, may address a selective therapeutic approach targeting the IL23/Th17 pathway. This review summarizes the current knowledge of the pathogenic contribution of Th17 cells in select cutaneous autoimmune disorders, including lupus erythematosus, scleroderma, dermatomyositis, bullous pemphigoid and pemphigus vulgaris. PMID:22824743
Chiricozzi, A; Zhang, S; Dattola, A; Cannizzaro, M V; Gabellini, M; Chimenti, S; Nistico, S P
The term pediatric autoimmune enteropathy was originally applied to a form of intractable diarrhea seen in children under the age of 6 months and characterized by male predominance, concurrent autoimmune-associated disorders, circulating gut autoantibodies, a lack of severe immunodeficiency and small bowel atrophy with prominent crypt apoptosis. However, recent studies have cast doubt over the specific clinicopathologic findings associated with this entity. We, therefore, collected 178 gastrointestinal biopsies from 14 patients and examined their clinical, serologic and pathologic findings. Patients at presentation ranged in age from birth to 15.9 years (median, 5.5 months; mean, 4.1 years) and included six males and eight females. All children suffered from chronic watery diarrhea and malnutrition. Concomitant-associated disorders were noted in 11 (79%) cases and included 10 (71%) with an immunodeficiency disorder and/or another autoimmune-related disease. Eleven patients (79%) were positive for anti-enterocyte antibodies. The salient findings of autoimmune enteropathy were most prominent in the small intestines and the majority (79%) of patients demonstrated villous blunting, crypt hyperplasia, mononuclear cell inflammatory expansion of the lamina propria and crypt apoptosis. The remaining (21%) patients showed marked intraepithelial lymphocytosis reminiscent of celiac disease. Further, acute cryptitis and crypt abscesses were seen in seven (50%) patients obscuring the presence of apoptosis. The absence of Paneth cells, goblet cells or both was noted in seven (50%) patients. Follow-up information was available for all patients with 13 (93%) receiving immunosuppressant therapy and demonstrating partial-to-complete response. In total, three patients died from continued diarrhea and sepsis with one decedent before treatment could be initiated. In summary, autoimmune enteropathy in children is a heterogenous disease with protean clinical and pathologic findings. Although anti-enterocyte antibodies were identified in the majority of the cases, their presence was variable and insensitive. In addition, pediatric autoimmune enteropathy was frequently encountered in the setting of immunodeficiency disorders. PMID:24051695
Singhi, Aatur D; Goyal, Alka; Davison, Jon M; Regueiro, Miguel D; Roche, Robyn L; Ranganathan, Sarangarajan
Summary Recent research on Anorexia Nervosa (AN) and Bulimia Nervosa (BN) has shown an increasing understanding of the biological and physiological abnormalities that underlie the development of an eating disorder. Cultural pressures, individual and family experiences, along with physiological and genetic systems all appear to contribute to the onset of these disorders. There is significant evidence for genetic factors in
Purpose of review The most relevant advances in immune-mediated movement disorders are described, with emphasis on the clinical–immunological associations, novel antigens, and treatment. Recent findings Many movement disorders previously considered idiopathic or degenerative are now recognized as immune-mediated. Some disorders are paraneoplastic, such as anti-CRMP5-associated chorea, anti-Ma2 hypokinesis and rigidity, anti-Yo cerebellar ataxia and tremor, and anti-Hu ataxia and pesudoathetosis. Other disorders such as Sydenham's chorea, or chorea related to systemic lupus erythematosus and antiphospholipid syndrome occur in association with multiple antibodies, are not paraneoplastic, and are triggered by molecular mimicry or unknown mechanisms. Recent studies have revealed a new category of disorders that can be paraneoplastic or not, and associate with antibodies against cell-surface or synaptic proteins. They include anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, which may cause dyskinesias, chorea, ballismus or dystonia (NMDAR antibodies), the spectrum of Stiff-person syndrome/muscle rigidity (glutamic acid decarboxylase, amphiphysin, GABAA-receptor-associated protein, or glycine receptor antibodies), neuromyotonia (Caspr2 antibodies), and opsoclonus–myoclonus–ataxia (unknown antigens). Summary Neurologists should be aware that many movement disorders are immune-mediated. Recognition of these disorders is important because it may lead to the diagnosis of an occult cancer, and a substantial number of patients, mainly those with antibodies to cell-surface or synaptic proteins, respond to immunotherapy.
Panzer, Jessica; Dalmau, Josep
Uveitis is a complex multifactorial autoimmune disease of the eye characterized by inflammation of the uvea and retina, degeneration of the retina, and blindness in genetically predisposed patients. Using the rat model of experimental autoimmune uveitis (EAU), we previously identified three quantitative trait loci (QTL) associated with EAU on rat chromosomes 4, 12, and 10 (Eau1, Eau2, and Eau3). The primary goal of the current study is to delineate additional non-MHC chromosomal regions that control susceptibility to EAU, and to identify any QTLs that overlap with the QTLs of other autoimmune diseases. Using a set of informative microsatellite markers and F(2) generations of resistant and susceptible MHC class II-matched rat strains (F344 and LEW), we have identified several new significant or suggestive QTLs on rat chromosomes 2, 3, 7, 10, and 19 that control susceptibility to EAU. A protective allele was identified in the susceptible LEW strain in the Eau5 locus at D7Wox18, and epistatic interactions between QTLs were found to influence the severity of disease. The newly identified regions (Eau4 through Eau9) colocalize with the genetic determinants of other autoimmune disease models, and to disease-regulating syntenic regions identified in autoimmune patients on human chromosomes 4q21-31, 5q31-33, 16q22-24, 17p11-q12, 20q11-13, and 22q12-13. Our results suggest that uveitis shares some of the pathogenic mechanisms associated with other autoimmune diseases, and lends support to the "common gene, common pathway" hypothesis for autoimmune disorders. PMID:18453595
Mattapallil, Mary J; Sahin, Azize; Silver, Phyllis B; Sun, Shu-Hui; Chan, Chi-Chao; Remmers, Elaine F; Hejtmancik, J Fielding; Caspi, Rachel R
Autoimmune-rheumatological diseases are worldwide distributed disorders and represent a complex array of illnesses characterized by autoreactivity (reactivity against self-antigens) of T-B lymphocytes and by the synthesis of autoantibodies crucial for diagnosis (biomarkers). Yet, the effects of the autoimmune chronic inflammation on the infiltrated tissues and organs generally lead to profound tissue and organ damage with loss of function (i.e., lung, kidney, joints, exocrine glands). Although progresses have been made on the knowledge of these disorders, much still remains to be investigated on their pathogenesis and identification of new biomarkers useful in clinical practice. The rationale of using proteomics in autoimmune-rheumatological diseases has been the unmet need to collect, from biological fluids that are easily obtainable, a summary of the final biochemical events that represent the effects of the interplay between immune cells, mesenchymal cells and endothelial cells. Proteomic analysis of these fluids shows encouraging results and in this review, we addressed four major autoimmune-rheumatological diseases investigated through proteomic techniques and provide evidence-based data on the highlights obtained in systemic sclerosis, primary and secondary Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis. PMID:21246742
De Franceschi, Lucia; Bosello, Silvia; Scambi, Cinzia; Biasi, Domenico; De Santis, Maria; Caramaschi, Paola; Peluso, Giusy; La Verde, Valentina; Bambara, Lisa Maria; Ferraccioli, Gianfranco
Children with protracted diarrhoea, circulating enterocyte autoantibodies, and an enteropathy showing features of inappropriate HLA molecule expression on the jejunal crypt epithelium, often present with persistent blood and mucus in their stools. Eight children with autoimmune enteropathy were investigated for the presence of associated colonic disease. Six children with protracted diarrhoea, no circulating autoantibodies, and an enteropathy (in five of them) undergoing colonoscopy were used as control subjects. In all eight patients, but not in the control subjects, there was macroscopic and microscopic evidence of an accompanying colitis of variable severity, thus indicating that a more generalised intestinal disorder was present, which might affect the whole intestine. Aberrant expression of DR molecules on the colonic surface and crypt epithelium was also detected. Autoimmunity may play a role in the colitis. Images Figure 1 Figure 2 Figure 3
Hill, S M; Milla, P J; Bottazzo, G F; Mirakian, R
BACKGROUND: We conducted a study in order to determine the usefulness and diagnostic value of International Autoimmune Hepatitis Group (IAHG) score in non-autoimmune hepatitis (AIH) hepatic disorders as well as in AIH\\/overlap syndromes and in cases with coexistence of AIH and other liver diseases. METHODS: We applied the IAHG score in 423 patients with liver diseases excluding patients with AIH,
Panagiotis A Papamichalis; Kalliopi Zachou; George K Koukoulis; Aikaterini Veloni; Efthimia G Karacosta; Lampros Kypri; Ioannis Mamaloudis; Stella Gabeta; Eirini I Rigopoulou; Ansgar W Lohse; George N Dalekos
Termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS), these cases of childhood-onset obsessive compulsive disorder and tic disorders resemble the presentation of Sydenham chorea, in that they have an acute onset following a group A beta-hemolytic streptococcal infection (group A Streptococcus), with accompanying neurological signs, and an episodic or sawtooth course. Familial associations of this subgroup of patients remain understudied. This report provides phenotypic descriptions of three youth with PANDAS as well as their genetically identical siblings (in two cases of twins and one case of triplets). These cases highlight the potential for environmental influences for discordant presentations in genetically identical siblings. Despite identical genetics, presentations showed marked variation across siblings (from a full PANDAS presentation to asymptomatic). Further research into environmentally driven influences such as postinfectious molecular mimicry and epigenetic factors that may influence the manifestation of these pediatric neuropsychiatric disorders will promote our understanding of their prevention and treatment. PMID:21486169
Lewin, Adam B; Storch, Eric A; Murphy, Tanya K
Abstract Question I have heard about children who have tic disorders that seem to be exacerbated by group A ?-hemolytic streptococcal infection. Should children presenting with this phenomenon receive treatment with antibiotics, receive prophylactic treatment, or use immunomodulators to treat the symptoms? Answer Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) constitute a condition that includes neuropsychiatric symptoms, mainly obsessive-compulsive disorder or tic disorders, temporally associated with an immune-mediated response to streptococcal infections. The actual existence of PANDAS as a unique clinical entity is still up for debate, as a temporal association between group A ?-hemolytic streptococcal infections and symptom exacerbations has been difficult to prove thus far. Based on only a few studies, positive results have been found using antibiotic prophylaxis and immunomodulatory therapy in children with PANDAS. At this time, however, evidence does not support a recommendation for long-term antibiotic prophylaxis or immunomodulatory therapy.
Tan, Jason; Smith, Christine H.; Goldman, Ran D.
Celiac disease is a common autoimmune disorder that has genetic, environmental, and immunologic components. It is characterized by an immune response to ingested wheat gluten and related proteins of rye and barley that leads to inflammation, villous atrophy, and crypt hyperplasia in the intestine. The disease is closely associated with genes that code for human leukocyte antigens DQ2 and DQ8. Transglutaminase 2 appears to be an important component of the disease, both as a deamidating enzyme that can enhance the immunostimulatory effect of gluten and as a target autoantigen in the immune response. Sensitive and specific serologic tests, including those for anti-transglutaminase antibody, are facilitating fast and noninvasive screening for celiac disease. Thus, they are contributing to a more accurate estimate of the prevalence of the disease and its association with other disorders. Celiac disease is associated with increased rates of anemia, osteoporosis, cancer, neurologic deficits, and additional autoimmune disorders. A gluten-free diet is the mainstay of safe and effective treatment of celiac disease, although its effect on some of the extraintestinal manifestations of the disease remains to be determined. PMID:15710962
Alaedini, Armin; Green, Peter H R
Background Several primary immune deficiency disorders are associated with autoimmunity and malignancy, suggesting a state of immune\\u000a dysregulation. The concept of immune dysregulation as a direct cause of autoimmunity in primary immune deficiency disorders\\u000a (PIDDs) has been strengthened by the recent discovery of distinct clinical entities linked to single-gene defects resulting\\u000a in multiple autoimmune phenomena including immune dysregulation, polyendocrinopathy, enteropathy and
D. Moraes-Vasconcelos; B. T. Costa-Carvalho; T. R. Torgerson; H. D. Ochs
Background & Aims: The relationship between celiac disease and many autoimmune disorders has been explained by the sharing of a common genetic factor. In a multicenter national study, we examined the relationship between the prevalence of autoimmune disorders in celiac disease and the duration of exposure to gluten. Methods: Over a 6-month period, 909 patients with celiac disease (group A;
Alessandro Ventura; Giuseppe Magazzů; Luigi Greco
Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) are frequently associated with clinical manifestations of autoimmune disorders (AD) and inflammatory response of the immune system. AD accompanying MDS and CMML include vasculitis, seronegative polyarthritis and neutrophilic dermatosis. Rare AD including relapsing polychondritis is strongly associated with MDS as in a high proportion of those patients MDS is diagnosed during disease course. Antinuclear antibodies (ANA) are frequently found among MDS patients without clinical manifestation of AD. In a subset of patients, MDS and resulting cytopenias appear to be the consequence of auto reactive immunologic activity and may respond to immunosuppressive treatment (IST). Increased release of inflammatory cytokines like tumor necrosis factor-(TNF)-? and interferon (IF)-? triggers apoptosis of myeloid precursor cells leading to cytopenias. Impaired function of immune cells including cytotoxic, regulatory (Treg), helper (Th17) T cells and NK cells also appears to predict response to IST, outcome and occurrence of AD. PMID:24507810
Braun, Thorsten; Fenaux, Pierre
During the course of chronic hepatitis C virus (HCV) infection, various extrahepatic manifestations of autoimmune disorders may occur, including arthralgia/arthritis, sicca complex, purpura, cutaneous ulcer, and thyroid dysfunction. In addition, the prevalence of circulating autoantibodies is high among patients with HCV infection. Commonly detected autoantibodies in HCV-infected patients include rheumatoid factor, antinuclear antibody, anti-SSA/anti-SSB antibody, cryoglobulin, antineutrophil cytoplasmic antibody, anti-smooth muscle antibody, anti-liver and anti-thyroid autoantibodies. These autoantibodies may be associated with underlying autoimmune disorders or liver inflammation in HCV infection. A possible reason for antibody production is overactivation and proliferation of B lymphocytes, via the interaction with the surface protein of HCV. Because immunotherapy can cause HCV flare-up or liver damage, overdiagnosis of HCV-related autoimmune symptoms as primary autoimmune disorders should be avoided. This review describes biomarkers that are useful in clinically evaluating autoimmune manifestations and disorders associated with HCV infection.
Yang, Deng-Ho; Ho, Ling-Jun; Lai, Jenn-Haung
Introduction: Patients with T-cell large granular lymphocytic leukemia (T-LGLL) have a high incidence of autoimmune disorders. The pathogenesis of associated T-LGLL and autoimmune abnormalities is not clear. In this study we have investigated the role of cytokines in the development of immune complications in LGLL. Patients and methods: Westudiedclinical andlaboratoryfeatures of15patientsdiagnosedwith T-LGLL. The patients had various autoimmune disturbances: persistent neutropenia,
Lev Shvidel; Chen Duksin; Alexandra Tzimanis; Mordechai Shtalrid; Abraham Klepfish; Erica Sigler; Michal Haran; Eran Eilat; Alain Berrebi
The lack of complete concordance of autoimmune disease in identical twins suggests that nongenetic factors play a major role in determining disease susceptibility. In this review, we consider how epigenetic mechanisms could affect the immune system and effector mechanisms in autoimmunity and/or the target organ of autoimmunity and thus affect the development of autoimmune diseases. We also consider the types of stimuli that lead to epigenetic modifications and how these relate to the epidemiology of autoimmune diseases and the biological pathways operative in different autoimmune diseases. Increasing our knowledge of these epigenetic mechanisms and processes will increase the prospects for controlling or preventing autoimmune diseases in the future through the use of drugs that target the epigenetic pathways.
Greer, Judith M; McCombe, Pamela A
Patients with systemic autoimmune diseases usually produce high levels of antibodies to self-antigens (autoantigens). The repertoire of common autoantigens is remarkably limited, yet no readily understandable shared thread links these apparently diverse proteins. Using computer prediction algorithms, we have found that most nuclear systemic autoantigens are predicted to contain long regions of extreme structural disorder. Such disordered regions would generally make poor B cell epitopes and are predicted to be under-represented as potential T cell epitopes. Consideration of the potential role of protein disorder may give novel insights into the possible role of molecular mimicry in the pathogenesis of autoimmunity. The recognition of extreme autoantigen protein disorder has led us to an explicit model of epitope spreading that explains many of the paradoxical aspects of autoimmunity – in particular, the difficulty in identifying autoantigen-specific helper T cells that might collaborate with the B cells activated in systemic autoimmunity. The model also explains the experimentally observed breakdown of major histocompatibility complex (MHC) class specificity in peptides associated with the MHC II proteins of activated autoimmune B cells, and sheds light on the selection of particular T cell epitopes in autoimmunity. Finally, the model helps to rationalize the relative rarity of clinically significant autoimmunity despite the prevalence of low specificity/low avidity autoantibodies in normal individuals.
Carl, Philip L; Temple, Brenda RS; Cohen, Philip L
Background. Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for many nonmalignant disorders, such as autoimmune disorders, inborn metabolic disorders, hemoglobinopathies, and immunodeficiency disorders. Autoimmune complications (AICs) after HSCT, such as autoimmune cytopenias, autoimmune hepatitis, primary biliary cirrhosis, and autoimmune cutaneous manifestations, are still neither well defined nor characterized. Patients. Between 2000 and 2012, 92 patients (47 males, 45 females) were treated with HSCT in our hospital, 51 with congenital hemoglobinopathies, 19 with primary immunodeficiency disease, 10 with metabolic disorders, five with Fanconi anemia, three with aplastic anemia, and four with familial hemophagocytic lymphohistiocytosis. Results. Mean age at HSCT was 6.4 years (range, 0.2–32 years) and mean duration of followup after HSCT was 6.81 years (range, 1–11 years). Sixteen (17.4%) patients developed chronic GVHD and five (5.4%) showed sclerodermatous features. Five (5.4%) patients were diagnosed with scleroderma manifestations, six (6.5%) with vitiligo, six (6.5%) with autoimmune hemolytic anemia (AIHA), six (6.5%) with idiopathic thrombocytopenia, three (3.3%) with mild leucopenia, two (2.2%) with aplastic anemia, two (2.2%) (one boy, one girl) with autoimmune thyroid disease, and one (1.1%) with autoimmune hepatitis. Conclusions. It was concluded that AICs are clinically significant complications after HSCT that contribute to morbidity but not to mortality. AICs are more frequent after HSCT for metabolic disorders, and sclerodermatous GVHD is more significant in children who underwent allogeneic HSCT for hemoglobinopathies. The potential to identify risk factors for AICs could lead to less morbidity and mortality and to maintain the patient's quality of life.
Khalil, Abdalla; Zaidman, Irena; Bergman, Reuven; Elhasid, Ronit; Ben-Arush, Myriam Weyl
Type 1, or cellular, immune response is characterized by overproduction of TNF-?, IFN-gamma, IL-1, IL-2 and IL-8 and is the underlying immune mechanism of psoriasis, alopecia areata, rheumatoid arthritis, Crohn's disease, multiple sclerosis, insulin-dependent diabetes mellitus and experimental autoimmune uveitis (EAU). Type 2 immune response is seen in antibody-mediated autoimmune diseases. Based on the pharmacokinetic effects of cetirizine and allopurinol,
M. R. Namazi
In this article, the authors use the term "overlaps" to refer to the coexistence of primary biliary cirrhosis (PBC) with another autoimmune condition that involves the liver or extrahepatic organs. Diagnosing PBC-autoimmune hepatitis (PBC-AIH) overlap syndrome remains a challenge, especially because there is still no consensus on the most appropriate diagnostic criteria. The prevalence of this condition varies considerably among series of PBC patients, and its treatment demands a combination of ursodeoxycholic acid and immunosuppressive drugs. Overlap syndrome between PBC and primary sclerosing cholangitis is described in exceptional cases. About one in three PBC patients have a concomitant extrahepatic autoimmune disease, which may include rheumatological, endocrinological, gastrointestinal, pulmonary, or dermatological conditions. Overlaps raise several questions, about whether they share much the same genetic susceptibility, as is generally assumed. The pathogenesis of these conditions includes the production of both innate and adaptive immune responses targeting cholangiocytes as well as different extrahepatic tissues. In this sense, overlaps in PBC represent a continuous spectrum of autoimmunity involving liver and extrahepatic tissues. PMID:25057958
Floreani, Annarosa; Franceschet, Irene; Cazzagon, Nora
Objectives A commonality across a number of pediatric neuropsychiatric disorders is a higher than typical rate of familial – and especially maternal – autoimmune disease. Of recent interest, a subtype of obsessive-compulsive disorder (OCD) and tic disorders known collectively as Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is believed to be secondary to central nervous system (CNS) autoimmunity that occurs in relation to group A streptococcal infection. Thus, we hypothesized that a sample of children with OCD and/or tics would have an increased maternal risk for an autoimmune response relative to population norms. We also expected maternal prevalence of various autoimmune diseases to be higher among those participants that met the putative criteria for PANDAS. Methods We examined, via structured interview, the medical history of the biological mothers of 107 children with OCD and/or tics. Results Autoimmune disorders were reported in 17.8% of study mothers, which is significantly greater than the general prevalence among women in the United States (approximately 5%). Further, study mothers were more likely to report having an autoimmune disease if their children were considered “likely PANDAS” cases versus “unlikely PANDAS” cases. Conclusions Results offer preliminary support for hypothesized links between maternal autoimmune disease and both OCD/tics and PANDAS in youth. Further research is necessary to clarify these general associations; links to specific autoimmune disease; and relevance of autoimmune disease in other family members (e.g., fathers).
Murphy, T.K.; Storch, E.A.; Turner, A.; Reid, J.M.; Tan, J.; Lewin, A.B.
Advances in understanding the pathogenesis of rheumatic diseases have led to the discovery of mechanisms of inflammation and\\u000a autoimmunity and have made possible the invention of new target-specific drugs. Biologic drugs, designed to inhibit specific\\u000a components of the immune system, such as cytokines, cytokine gene expression, and their complex interactions, have revolutionized\\u000a the treatment options in pediatric rheumatology. Only three
Luciana Breda; Marianna Del Torto; Sara De Sanctis; Francesco Chiarelli
Concerns are raised regarding recent claims of an association between left-handedness and autoimmune disease and\\/or dyslexia. The available data provide only marginal support at best for these claims which, in addition, contain potentially misleading implications about left-handedness. Furthermore, some of the theoretical bases for the proposed associations are inconsistent with the relevant literature. Revisions in the theory are suggested to
Paul Satz; Henry V. Soper
Background Chronic idiopathic urticaria (CU) has been associated with other autoimmune diseases and basophil-activating autoantibodies to Fc?RI or IgE. It is unknown whether patients with systemic-autoimmune diseases have a similar prevalence of these autoantibodies. Objective To compare the prevalences of basophil-activating autoantibodies (elevated CU Index) in patients with CU, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Clinical characteristics and laboratory studies were examined for an association with the CU Index. Methods Adult patients, 27 with CU, 27 with RA, and 26 with SLE, and 20 healthy controls were compared on the basis of the CU Index panel, anti-IgE, and antithyroid antibodies. Results The CU Index values were significantly higher in the CU group when compared with the RA group but not when compared with the SLE group. 33% of CU, 23% of SLE, 3.7% of RA, and 15% of controls had apositive CU Index. Elevated antithyroid antibody levels did not correlate with a positive CU Index in any of the groups. An elevated CU Index in the SLE group was not associated with age, sex, ethnicity, disease severity, or history of atopy. Conclusion The CU Index values were elevated in patients with CU and SLE. The presence of these autoantibodies did not correlate with disease activity or presence of thyroid antibodies. Functional autoantibodies may not be specific for chronic idiopathic urticaria, and their role in nonurticarial systemic autoimmune diseases requires further investigation.
Cho, Christine B.; Stutes, Shahan A.; Altrich, Michelle L.; Ardoin, Stacy P.; Phillips, Gary; Ogbogu, Princess U.
Autoimmune Addison's disease (AAD) is the main reason of primary adrenal failure. More than a half of patients display additional autoimmune conditions, which represent a considerable clinical concern. This study aimed to investigate the prevalence of concomitant autoimmune disorders in 85 Polish AAD patients (61 females, 24 males). Mean age at AAD onset was 34.6 ± 12.6 years, significantly earlier in males (P < 0.001). Sixty-nine patients presented positive serum antibodies to 21-hydroxylase and shorter AAD duration than those with negative results (P = 0.027). Seventy-three subjects suffered from coexisting autoimmune disorders. Serum autoantibodies against thyreoperoxidase, thyroglobulin, TSH receptor, glutamic acid decarboxylase, insulin, tyrosine phosphatase-like protein IA2, parietal cell H(+)/K(+)-ATPase, intrinsic factor and tissue transglutaminase were detectable in 71.8, 41.2, 4.7, 21.0, 4.9, 2.5, 49.4, 12.0 and 3.5% of patients, respectively. Antinuclear antibodies were found in 12.5%. Thyroid autoimmunity was most common (46 subjects with lymphocytic thyroiditis, 19 with Graves' disease), followed by atrophic gastritis (29.4%), pernicious anaemia (11.8%), hypergonadotropic hypogonadism (8.2%), vitiligo (8.2%), type 1 diabetes (7.1%), celiac disease (3.5%) and alopecia (2.4%). Gender differences were observed only for thyroid autoimmunity. Current study confirms particular tendency of AAD patients to develop other autoimmune disorders. Active search for concomitant conditions is warranted to prevent serious complications. PMID:20960274
Fichna, Marta; Fichna, Piotr; Gryczy?ska, Maria; Walkowiak, Jaros?aw; Zurawek, Magdalena; Sowi?ski, Jerzy
Cooccurrences of chronic lymphocytic thyroiditis (CLT) and thyroid cancer (DTC) have been repeatedly reported. Both CLT and DTC, mainly papillary thyroid carcinoma (PTC), share some epidemiological and molecular features. In fact, thyroid lymphocytic inflammatory reaction has been observed in association with PTC at variable frequency, although the precise relationship between the two diseases is still debated. It also remains a matter of debate whether the association with a CLT or even an autoimmune disorder could influence the prognosis of PTC. A better understanding about clinical implications of autoimmunity in concurrent thyroid cancer could raise new insights of thyroid cancer immunotherapy. In addition, elucidating the molecular mechanisms involved in autoimmune disease and concurrent cancer allowed us to identify new therapeutic strategies against thyroid cancer. The objective of this article was to review recent literature on the association of these disorders and its potential significance.
Cunha, L. L.; Ferreira, R. C.; Marcello, M. A.; Vassallo, J.; Ward, L. S.
The present invention provides compositions and methods for preventing and treating gastrointestinal disorders by administering to a subject an effective amount of secretin either alone or in combination with an effective amount of oxytocin. The invention also provides compositions and methods for preventing and treating central nervous system disorders by administering to a subject an effective amount of secretin in combination with an effective amount of oxytocin. The invention further provides compositions and methods for treating and preventing a variety of autoimmune diseases by administering to a subject an effective amount of secretin in combination with an effective amount of oxytocin. Additionally, the invention provides compositions and methods for preventing and treating pain by administering to a subject using a combination of an effective amount of secretin and an effective amount of oxytocin. The invention also provides kits for use in treating and/or preventing gastrointestinal disorders, central nervous system disorders, autoimmune diseases and pain comprising a combination of secretin and oxytocin.
The first use of immunoglobulin therapy, historically, was in 1890 when Emil von Behring developed effective antiserum against diphtheria toxin, but only in the early 1970s technological advancements in the fractionation of plasma lead to the production of Ig preparations which could be administered intravenously. Intravenous Ig products are a mainstay for disorders such as: primary immunodeficiency, serious infections, autoimmune and inflammatory disorders. During autoimmune and systemic inflammatory disease IVIg exhibits a number of immune modulatory activities such as: Fc Receptor-mediated effects, modulation of complement, modulation of cytokine production, superantigens neutralization, antibodies neutralization by idiotype network, increased catabolism of IgG, but also biologic effects of other molecules present in IVIg preparations. Recent understanding about IVIg composition and mechanism of action can explain its therapeutic effect in autoimmune and inflammatory disorders. Nevertheless it is important to underline that IVIg is a heterogeneous product and it is difficult to determine the exact mechanism of its activities in every disease. The increased use of IVIg in the treatment of autoimmune disorders outlined the issue of tolerability. Undesiderable effects to IVIg occurs in less than 5% of patients. PMID:12032582
Emmi, L; Chiarini, F
Streptococcal infection in children is usually benign and self-limited. In a small percentage of children, prominent neurologic and\\/or psychiatric sequelae can occur. Sydenham chorea is the best defined and best recognized. PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) is a well-defined syndrome in which tics (motor and\\/or vocal) and\\/or obsessive-compulsive disorder consistently exacerbate in temporal correlation to a
Piero Pavone; Enrico Parano; Renata Rizzo; Rosario R. Trifiletti
The clinical use of autologous stem cell transplants for the treatment of refractory severe autoimmune diseases was preceded by convincing proof of its underlying principle in animal models. The various categories of experimental autoimmune disease in laboratory rodents are briefly described here, and the rationale that was used in the selection of suitable experimental autoimmune diseases for translational research is explained. The two models that provided the bulk of the data needed for designing the initial clinical treatment protocols were adjuvant arthritis (AA) and experimental allergic encephalomyelitis (EAE), which were both induced in Buffalo rats. In this strain, AA is manifested as a chronic, progressive, systemic polyarthritis and EAE as a chronic, remitting/relapsing form of encephalomyelitis resembling multiple sclerosis. Both diseases can be cured with autologous stem cell transplantation provided that adequate conditioning is given and that the disease has not yet progressed to the stage of 'scarring'. It is basically the inflammatory stages that respond well to this therapy. The success of treatment depends on how completely the autoantigen-specific activated T-lymphocytes and memory cells are eradicated. Because of a lack of information on the nature of the autoantigens involved in human disease and on the size of those cell populations in the animal models as well as in humans, this aspect of translation is difficult. The experiments have, however, provided important guidelines. High-dose conditioning regimens yield better results than low-dose conditioning, certain conditioning agents perform better than others, and care should be taken not to reintroduce too many T-cells with the autologous graft. The clinical results obtained so far indicate a high predictive power of these two animal models, which are therefore recommended strongly for additional preclinical studies. PMID:15302335
van Bekkum, Dirk W
Abstract Obsessive-compulsive disorder (OCD) and related conditions including Tourette's disorder (TD) are chronic, relapsing disorders of unknown etiology associated with marked impairment and disability. Associated immune dysfunction has been reported and debated in the literature since the late 80s. The immunologic culprit receiving the most interest has been Group A Streptococcus (GAS), which began to receive attention as a potential cause of neuropsychiatric symptoms, following the investigation of the symptoms reported in Sydenham's chorea (SC) and rheumatic fever, such as motor tics, vocal tics, and both obsessive-compulsive and attention deficit/hyperactivity symptoms. Young children have been described as having a sudden onset of these neuropsychiatric symptoms temporally associated with GAS, but without supporting evidence of rheumatic fever. This presentation of OCD and tics has been termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS). Of note, SC, OCD, and TD often begin in early childhood and share common anatomic areas—the basal ganglia of the brain and the related cortical and thalamic sites—adding support to the possibility that these disorders might share a common immunologic and/or genetic vulnerability. Relevant manuscripts were identified through searches of the PsycINFO and MedLine databases using the following keywords: OCD, immune, PANDAS, Sydenham chorea, Tourette's disorder Group A Streptococcus. Articles were also identified through reference lists from research articles and other materials on childhood OCD, PANDAS, and TD between 1966 and December 2010. Considering the overlap of clinical and neuroanatomic findings among these disorders, this review explores evidence regarding the immunobiology as well as the relevant clinical and therapeutic aspects of TD, OCD, and PANDAS.
Kurlan, Roger; Leckman, James
Obsessive-compulsive disorder (OCD) and related conditions including Tourette's disorder (TD) are chronic, relapsing disorders of unknown etiology associated with marked impairment and disability. Associated immune dysfunction has been reported and debated in the literature since the late 80s. The immunologic culprit receiving the most interest has been Group A Streptococcus (GAS), which began to receive attention as a potential cause of neuropsychiatric symptoms, following the investigation of the symptoms reported in Sydenham's chorea (SC) and rheumatic fever, such as motor tics, vocal tics, and both obsessive-compulsive and attention deficit/hyperactivity symptoms. Young children have been described as having a sudden onset of these neuropsychiatric symptoms temporally associated with GAS, but without supporting evidence of rheumatic fever. This presentation of OCD and tics has been termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS). Of note, SC, OCD, and TD often begin in early childhood and share common anatomic areas--the basal ganglia of the brain and the related cortical and thalamic sites--adding support to the possibility that these disorders might share a common immunologic and/or genetic vulnerability. Relevant manuscripts were identified through searches of the PsycINFO and MedLine databases using the following keywords: OCD, immune, PANDAS, Sydenham chorea, Tourette's disorder Group A Streptococcus. Articles were also identified through reference lists from research articles and other materials on childhood OCD, PANDAS, and TD between 1966 and December 2010. Considering the overlap of clinical and neuroanatomic findings among these disorders, this review explores evidence regarding the immunobiology as well as the relevant clinical and therapeutic aspects of TD, OCD, and PANDAS. PMID:20807070
Murphy, Tanya K; Kurlan, Roger; Leckman, James
BACKGROUND AND AIMS—Duration of gluten exposure seems to predispose adolescents with coeliac disease to autoimmune diseases. In a retrospective cohort study, we assessed the relationship between autoimmune disorders and actual gluten exposure in patients in whom coeliac disease was diagnosed in adult life (?16 years).?METHODS—We screened for the presence of autoimmunity in 605 controls (16-84 years) and 422 patients (16-84 years), all of whom had been on gluten withdrawal for at least one year (median follow up 9.5 years). A logistic regression analysis, setting the prevalence of autoimmunity as the dependent variable, was employed to control for independent covariates as predictors of the risk of autoimmunity.?RESULTS—The prevalence of autoimmunity was threefold higher (p<0.00001) in patients than in controls. Mean duration of gluten exposure was 31.2 and 32.6 years for patients with or without autoimmunity. Logistic regression showed that increased age at diagnosis of coeliac disease was related to the prevalence of autoimmune disease while "actual gluten exposure" which takes into account diet compliance, follow up, and age at diagnosis of autoimmune disorders were not predictive for the risk of developing autoimmune diseases (odds ratio 0.82 per year).?CONCLUSION—The prevalence of autoimmune diseases in patients with a late coeliac disease diagnosis does not correlate with duration of gluten intake. Early exposure to gluten may modify the immunological response. Gluten withdrawal does not protect patients with a late diagnosis from autoimmune diseases.???Keywords: coeliac disease; autoimmune disorders; prevalence
Sategna, G; Solerio, E; Scaglione, N; Aimo, G; Mengozzi, G
BACKGROUND AND AIMSDuration of gluten exposure seems to predispose adolescents with coeliac disease to autoimmune diseases. In a retrospective cohort study, we assessed the relationship between autoimmune disorders and actual gluten exposure in patients in whom coeliac disease was diagnosed in adult life (?16 years).METHODSWe screened for the presence of autoimmunity in 605 controls (16–84 years) and 422 patients (16–84
C Sategna Guidetti; E Solerio; N Scaglione; G Aimo; G Mengozzi
OBJECTIVES This study aimed to examine whether pediatric autoimmune neuropsychiatric disorders associated with streptococcus were appropriately diagnosed in the community and to determine subsequent rates of unwarranted use of antibiotic treatment for tics and obsessive-compulsive symptoms without the identification of an infection. METHODS The design was a retrospective, cross-sectional, observational study of 176 children and adolescents who were evaluated in a specialty program for tics, Tourette's disorder, and related problems. Previously published diagnostic criteria were used to establish the diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus in our clinic. RESULTS Subjects were significantly less likely to receive a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus at the specialty clinic than in the community. In the community, subjects were significantly more likely to be treated with antibiotics or immunosuppressant medication if they received a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus. Of the 27 subjects with a community diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus who were treated with antibiotics, 22 (82%) were treated without laboratory evidence of an infection; 2 were treated with immunomodulatory medications. CONCLUSIONS Our results support our hypothesis that pediatric autoimmune neuropsychiatric disorders associated with streptococcus are frequently diagnosed in the community without the application of all working diagnostic criteria. This phenomenon has resulted in unwarranted use of antibiotic treatment for tics/obsessive-compulsive disorder without evidence of laboratory infection.
Gabbay, Vilma; Coffey, Barbara J.; Babb, James S.; Meyer, Laura; Wachtel, Carly; Anam, Seeba; Rabinovitz, Beth
Primary antithrombotic prevention with aspirin is not indicated in asymptomatic patients with confirmed antiphospholipid (aPL) positivity without systemic autoimmune disorders because: a) the estimated prevalence of thrombosis in unselected cases is about 1% patient-years (range 0-2.8); b) this level of thrombotic risk is equivalent to that of major bleeding associated with the use of aspirin and therefore the expected benefit does not outweigh the risk; c) these expectations have been confirmed by at least one randomized clinical trial, although with methodological limits. The management of modifiable thrombotic risk factors can be an alternative and safer strategy, considering that many vascular events occur in the presence of concomitant non-aPL triggering conditions. Whether primary prophylaxis with aspirin may be useful for some subsets of aPL patients at particularly high thrombotic risk, such as those with overt systemic autoimmune disorders or with special patterns of antibodies ('triple positivity'), remains to be established. PMID:22635221
We review the neuronal antibodies described in CNS disorders in order to clarify their diagnostic value, emphasize potentials\\u000a pitfalls and limitations in the diagnosis of paraneoplastic neurological syndromes (PNS), and examine the current evidence\\u000a for a possible pathogenic role. We propose to classify the neuronal antibodies associated with syndromes resulting from CNS\\u000a neuronal dysfunction into two groups according to the
Francesc Graus; Albert Saiz; Josep Dalmau
Pemphigus is a relatively rare autoimmune bullous disorder involving the skin and mucous epithelia. Clinically characterized\\u000a by blisters and erosions, its histological hallmark is acantholysis induced by IgG antibodies (ab) against desmoglein 3 and\\/or\\u000a desmoglein 1. The role of ab alone in inducing acantholysis is still a matter of debate as several mechanisms could be involved.\\u000a Another intriguing area of
Christian Veldman; Claudio Feliciani
Thymoma-associated multi-organ autoimmunity is a rare, autoimmune disease that causes colitis, liver dysfunction and cutaneous graft-versus-host (GVH)-like skin damage. This paraneoplastic autoimmune disorder may be due to inadequate T cell selection in the tumour environment of the thymus. Although sporadic case reports have revealed its clinical features, little is known about its pathological mechanism. By comparing the skin-infiltrating T cell subsets with those of GVH disease (GVHD) and other inflammatory skin diseases, we sought to elucidate the pathological mechanism of thymoma-associated multi-organ autoimmunity. Histopathological and immunohistochemical analysis of skin biopsies was performed for three patients with thymoma-associated multi-organ autoimmunity. Histopathological findings of thymoma-associated multi-organ autoimmunity were indistinguishable from those of patients with acute GVHD, although the aetiologies of these diseases are completely different. The frequency of regulatory T cells (T(regs)) is reduced in cutaneous lesions and CD8+ cytotoxic T lymphocytes that massively infiltrate into the epidermis of patients with thymoma-associated multi-organ autoimmunity. Additionally, the ratio of T helper type 17 (Th17) cells to CD4+ cells in patients with thymoma-associated multi-organ autoimmunity and acute GVHD was higher than that in healthy controls, but similar to that in psoriasis vulgaris patients. Similarity of the skin-infiltrating T cell subsets with those of acute GVHD suggested that skin damage in patients with thymoma-associated multi-organ autoimmunity might be induced by self-reactive cytotoxic T lymphocytes under the diminished suppressive capacity of T(regs). PMID:21985362
Hanafusa, T; Azukizawa, H; Kitaba, S; Murota, H; Umegaki, N; Terao, M; Sano, S; Nakagiri, T; Okumura, M; Katayama, I
The study was designed to test further the usefulness of the radioreceptor assay of thyroid stimulating hormone (TSH) binding inhibitory immunoglobulins (TBII) and the bioassay of thyroid stimulating antibodies (TSAb) or TSH stimulated cAMP response inhibitory antibodies (TBkAb) in the prediction of neonatal thyroid dysfunction. Of 63 pregnant women with a current or past history of autoimmune thyroid disorder, 11 (one with active and six with a past history of Graves' disease and four with autoimmune thyroiditis) gave birth to a baby with transient hyper or hypo-thyroidism. Only high maternal titres (which could persist after partial thyroidectomy) of anti TSH-receptor antibodies (TRAb) led to neonatal hyperthyroidism. Both types of assay were able to detect the antibodies responsible for transitory neonatal autoimmune thyroid disease. TBII values reflected TSAb titres so that there was a significant correlation between the results of both assays in women with Graves' disease and in neonatal sera. Positive TBII and TBkAb activities were present in 5 of the 28 women with autoimmune thyroiditis. Therefore, when TBII is positive, the functional characterization of the antibodies warrants the use of the bioassay. PMID:1979233
Clavel, S; Madec, A M; Bornet, H; Deviller, P; Stefanutti, A; Orgiazzi, J
A multicenter study of 308 children with Autism Spectrum Disorder (ASD) was conducted through the Collaborative Programs of Excellence in Autism (CPEA), sponsored by the National Institute of Child Health and Human Development, to compare the family history of autoimmune disorders in children with ASD with and without a history of regression. A…
Molloy, Cynthia A.; Morrow, Ardythe L.; Meinzen-Derr, Jareen; Dawson, Geraldine; Bernier, Raphael; Dunn, Michelle; Hyman, Susan L.; McMahon, William M.; Goudie-Nice, Julie; Hepburn, Susan; Minshew, Nancy; Rogers, Sally; Sigman, Marian; Spence, M. Anne; Tager-Flusberg, Helen; Volkmar, Fred R.; Lord, Catherine
The transgenic (tg) expression of interleukin (IL)-4 under the control of a major histocompatibility complex (MHC) class I promoter leads to B cell hyperactivity in mice, characterized by increased B cell surface MHC class II and CD23 expression, elevated responsiveness of the B cells to polyclonal ex vivo stimulation, and increased immunoglobulin (Ig)G1 and IgE serum levels. Tg mice develop anemia, glomerulonephritis with complement and immune deposition in the glomeruli, and show increased production of autoantibodies. Treatment of IL-4 tg mice with anti-IL-4 neutralizing antibodies protected the mice from disease development, showing that IL-4 was responsible for the observed disorders. Deletion of superantigen responsive autoreactive T cells in the IL-4 tg mice was normal and treatment of mutant mice with deleting anti-CD4 antibodies failed to ablate the onset of autoimmune-like disease, suggesting that CD4+T cells were not the primary cause of the disorders. Furthermore, the deletion of B cells reacting against MHC class I molecules was also normal in the IL-4 tg mice. Therefore the most likely explanation for the increased production of autoantibodies and the autoimmunelike disorders is that IL-4 acts directly on autoreactive B cells by expanding them in a polyclonal manner. Taken together our results show that inappropriate multi-organ expression of IL-4 in vivo leads to autoimmune-type disease in mice.
Erb, Klaus J.; Ruger, Beate; von Brevern, Maja; Ryffel, Bernhard; Schimpl, Annelise; Rivett, Karen
Perianal streptococcal dermatitis is an infection caused by group A streptococcus (GAS). Children with a pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) phenotype may have tics or obsessive compulsive symptoms secondary to a systemic immune activation by GAS infecting perianal areas. In this retrospective case series, the authors describe three children with symptoms consistent with PANDAS and a confirmed perianal streptococcal dermatitis as the likely infectious trigger. Concomitant perianal dermatitis and new-onset obsessive-compulsive symptoms and/or tics are strong indications for perianal culture and rapid antigen detection test in young children. PMID:24763762
Toufexis, Megan; Deoleo, Caroline; Elia, Josephine; Murphy, Tanya K
NKT cells are a heterogeneous subset of specialized, self-reactive T cells, with innate and adaptive immune properties, which allow them to bridge innate and adaptive immunity and profoundly influence autoimmune and malignant disease outcomes. NKT cells mediate these activities through their ability to rapidly express pro- and anti-inflammatory cytokines that influence the type and magnitude of the immune response. Not only do NKT cells regulate the functions of other cell types, but experimental evidence has found NKT cell subsets can modulate the functions of other NKT subsets. Depending on underlying mechanisms, NKT cells can inhibit or exacerbate autoimmunity and malignancy, making them potential targets for disease intervention. NKT cells can respond to foreign and endogenous antigenic glycolipid signals that are expressed during pathogenic invasion or ongoing inflammation, respectively, allowing them to rapidly react to and influence a broad array of diseases. In this article we review the unique development and activation pathways of NKT cells and focus on how these attributes augment or exacerbate autoimmune disorders and malignancy. We also examine the growing evidence that NKT cells are involved in liver inflammatory conditions that can contribute to the development of malignancy.
Subleski, Jeff J; Jiang, Qun; Weiss, Jonathan M; Wiltrout, Robert H
Abstract Neuromyelitis optica (NMO) is an immune-mediated neurological disorder characterised by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis. A serum biomarker, aquaporin-4 IgG, the autoantibody against aquaporin-4 water channel, has been specifically associated with NMO and has assisted early recognition and prediction of relapses. Less commonly, a monophasic course, associated with antibodies to myelin oligodendrocyte glycoprotein has been reported. Specific diagnostic criteria have been defined; however, some cases that do not fulfil these criteria (but are nevertheless associated with aquaporin-4 IgG) are classified as NMO spectrum disorder and follow the same relapsing course. An ever-growing list of autoimmune disorders, both organ-specific and non-organ-specific, have been associated in up to 20-30% of patients with NMO. These disorders, which may become symptomatic before or after the development of NMO, are often diagnosed long after the diagnosis of NMO, as symptoms may be wrongly attributed to NMO, its residual effects or medication side effects. In addition, autoantibodies can be found in patients with NMO without coexisting disease (up to 40% in some series) and maybe suggestive of a heightened humoral immune response. We present a comprehensive review of the current literature on autoimmune disorders co-existing with NMO and identified 22 autoimmune conditions (myasthenia gravis, coeliac disease, ulcerative colitis, sclerosing cholangitis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid antibody syndrome, Sjogren's syndrome, autoimmune hypothyroidism, immune thrombocytopenic purpura, pernicious anaemia, narcolepsy, pemphigus foliaceus, alopecia areata, psoriasis, scleroderma, dermatitis herpetiformis, polymyositis, chronic inflammatory demyelinating polyneuropathy, paraneoplastic disorders, insulin dependent diabetes mellitus and autoimmune encephalitis). PMID:24512514
Iyer, Anand; Elsone, Liene; Appleton, Richard; Jacob, Anu
Reactions of innate immunity include phagocytosis, the production and activity of cytokines, chemokines, and adhesion molecules, the killing of infected or changed cells by NK cells and complement activated by natural lectins, and the cytokine-dependent resistance of leukocytes to viral infection. All these mechanisms maintain innate immunity. Deficiency in this immunity is sometimes accompanied by frequent bacterial and viral infections. When innate immunity is permanently stimulated and the intensity of the reactions is stronger, these mechanisms may be directed against the host and subsequently stimulate acquired immunity (antibody and cellular immunity). A higher production of cytokines, oxidative stress, and a high production of NO accompany autoimmunity and neurodegeneration. The possible participation of innate immune receptors, cytokines, and other factors in the development of autoimmune and neurodegenerative diseases is discussed. The importance and possible role of blood-derived microglial cells in the prevention or elimination of amyloid deposits and plaque formation is described. A possible regulatory system, based on the presence of suppressors of cytokine signaling (SOCS), receptors of the Tyro-3 family, adenosine and adenosine phosphates, and IL-10, is reviewed. This review presents the mechanisms involved in the control of the innate immune response by microglia in the development of neurodegenerative disorders.
Blach-Olszewska, Zofia; Leszek, Jerzy
During nearly a decade of research dedicated to the study of sphingosine signaling pathways, we identified sphingosine-1-phosphate lyase (S1PL) as a drug target for the treatment of autoimmune disorders. S1PL catalyzes the irreversible decomposition of sphingosine-1-phosphate (S1P) by a retro-aldol fragmentation that yields hexadecanaldehyde and phosphoethanolamine. Genetic models demonstrated that mice expressing reduced S1PL activity had decreased numbers of circulating lymphocytes due to altered lymphocyte trafficking, which prevented disease development in multiple models of autoimmune disease. Mechanistic studies of lymphoid tissue following oral administration of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)-imidazole (THI) 3 showed a clear relationship between reduced lyase activity, elevated S1P levels, and lower levels of circulating lymphocytes. Our internal medicinal chemistry efforts discovered potent analogues of 3 bearing heterocycles as chemical equivalents of the pendant carbonyl present in the parent structure. Reduction of S1PL activity by oral administration of these analogues recapitulated the phenotype of mice with genetically reduced S1PL expression. PMID:19489538
Bagdanoff, Jeffrey T; Donoviel, Michael S; Nouraldeen, Amr; Tarver, James; Fu, Qinghong; Carlsen, Marianne; Jessop, Theodore C; Zhang, Haiming; Hazelwood, Jill; Nguyen, Huy; Baugh, Simon D P; Gardyan, Michael; Terranova, Kristen M; Barbosa, Joseph; Yan, Jack; Bednarz, Mark; Layek, Suman; Courtney, Lawrence F; Taylor, Jerry; Digeorge-Foushee, Ann Marie; Gopinathan, Suma; Bruce, Debra; Smith, Traci; Moran, Liam; O'Neill, Emily; Kramer, Jeff; Lai, Zhong; Kimball, S David; Liu, Qingyun; Sun, Weimei; Yu, Sean; Swaffield, Jonathan; Wilson, Alan; Main, Alan; Carson, Kenneth G; Oravecz, Tamas; Augeri, David J
Dendritic cells (DC), considered as immunological sentinels of the organism since they are antigen presenting cells, create the link between innate and adaptive immunity. DC include myeloid dendritic cells (MDC) and plasmacytoid dendritic cells (PDC). The presence of PDC, cells capable of producing large quantities of interferon alpha (IFN-?) in response to pathogenic agents or danger signals, seem to be tightly related to pathological conditions. Thereby, PDC have been observed in inflammatory immunoallergic dermatological disorders, in malignant cutaneous tumours and in cutaneous lesions of infectious origin. They seem to play a crucial role in the initiation of the pathological process of autoimmune diseases such as lupus or psoriasis. Their function within a tumour context is not as well known and is controversial. They could have a tolerogenic role towards tumour cells in the absence of activator but they also have the capacity to become activated in response to Toll-like receptor (TLR) ligands and could therefore be usefull for therapeutic purposes.
Charles, Julie; Chaperot, Laurence; Salameire, Dimitri; Di Domizio, Jeremy; Aspord, Caroline; Gressin, Remy; Jacob, Marie-Christine; Richard, Marie-Jeanne; Beani, Jean-Claude; Plumas, Joel; Leccia, Marie-Therese
Streptococcal infection in children is usually benign and self-limited. In a small percentage of children, prominent neurologic and/or psychiatric sequelae can occur. Sydenham chorea is the best defined and best recognized. PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive-compulsive disorder consistently exacerbate in temporal correlation to a group A beta-hemolytic streptococcal infection. PANDAS constitutes a subset of children with tics, Tourette syndrome, and obsessive-compulsive disorder. In addition to strictly defined PANDAS, we and others have recognized several PANDAS variants, including adult-onset variant, a dystonic variant, a myoclonic variant, and a "chronic" PANDAS variant. The nosology and classification of these entities are rapidly evolving. The recognition that some pediatric neurobehavioral syndromes have infectious and/or immunologic triggers points to important new avenues of disease treatment. In this review, we summarize this complex and rapidly evolving area of clinical research. PMID:16970875
Pavone, Piero; Parano, Enrico; Rizzo, Renata; Trifiletti, Rosario R
Recurrent pregnancy loss has been associated with autoimmune responses to membrane phospholipids and alloimmune reactions against paternally derived molecules on the trophoblast. The problem is psychologically and economically stressful as it undermines the capacity of some couples to reproduce and participate effectively in the day-to-day economic activities. This article reviews the adoption of intravenous immunoglobulin as a form of therapy for the clinical management of recurrent pregnancy loss and of selected autoimmune disorders. Side effects, contraindications and safety of use are discussed. PMID:15147144
Omwandho, Charles O A; Gruessner, Susanne E M; Roberts, Timothy K; Tinneberg, Hans Rudolf
Non-endocrine events represent a heterogeneous group of complications occurring in children who survive long term after haematopoietic SCT. This review highlights the late sequel in a growing child. The preparative regimen itself with high-dose chemotherapy and\\/or radiotherapy (TBI) or the treatment given before the transplant procedure may cause organ damage with permanent sequel. Immune reconstitution and chronic GvHD have crucial
M Faraci; A N Békássy; V De Fazio; A Tichelli; G Dini
Autoimmune polyglandular syndromes are defined as a spectrum of association between 2 or more organ specific endocrinopaties and non-endocrine autoimmune diseases. Autoimmune polyglandular syndromes type 2 is characterized by the coexistence of adrenal failure with autoimmune thyroid disease and diabetes mellitus type 1. Inflammatory bowel diseases are rarely associated with these autoimmune disorders. Here, we report about a case of 33 years old male with known history of Crohn's colitis diagnosed in childhood. In 2003 the patient experienced sudden loss of hair, eyebrows, eyelashes, beard and body hair - alopecia universalis was diagnosed. At the age of 28, the patient was hospitalized with severe dehydration and clinical signs of ketoacidosis. Increased blood glucose (40 mmol/L), ketonuria and metabolic acidosis indicated diabetes mellitus type 1. In 2005, he had severe relapse of Crohn's disease and was treated with systemic corticosteroid. Although patient responded well to the induction therapy, fatigue, hypotension, bradycardia called for further investigations: free thyroxine - 6.99 pmol/L, thyroid-stimulating hormone >75 U/ml, anti-thyroid peroxidase antibodies >1000 U/mL, so diagnosis of Haschimoto thyroiditis was confirmed. Persistent hypotension and fatigue, recurrent hypoglycemic crises indicated a possible presence of hypo-function of adrenal glands. After complete withdrawal of corticosteroid therapy, low cortisol levels (69.4 nmol/L) and positive tetracosactide stimulation test proved adrenal cortex failure. Regardless of the intensive treatment for diabetes, hypothyroidism, adrenal insufficiency and Crohn's disease, it was extremely difficult to achieve and maintain control of all four diseases. PMID:22677116
Protic, Marijana; Gligorijevic, Vladimir; Bojic, Daniela; Popovic, Bojana; Damjanovic, Svetozar; Jojic, Njegica
In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4(+)HLA-DR(+), CD8(+) T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-?/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection. PMID:23936564
Coelho-dos-Reis, Jordana Grazziela Alves; Passos, Livia; Duarte, Mariana Costa; Araújo, Marcelo Grossi; Campi-Azevedo, Ana Carolina; Teixeira-Carvalho, Andréa; Peruhype-Magalhăes, Vanessa; Trindade, Bruno Caetano; Dos Santos Dias, Raquel; Martins, Marina Lobato; Carneiro-Proietti, Anna Barbara de Freitas; Guedes, Antônio Carlos; Gonçalves, Denise Utsch; Martins-Filho, Olindo Assis
Dendritic cells (DC), considered as immunological sentinels of the organism since they are antigen presenting cells, create the link between innate and adaptive immunity. DC include myeloid dendritic cells (MDC) and plasmacytoid dendritic cells (PDC). The presence of PDC, cells capable of producing large quantities of interferon alpha (IFN-alpha) in response to pathogenic agents or danger signals, seems to be closely related to pathological conditions. PDC have been observed in inflammatory immunoallergic dermatological disorders, in malignant cutaneous tumours and in cutaneous lesions of infectious origin. They seem to play a crucial role in the initiation of the pathological processes of autoimmune diseases such as lupus or psoriasis. Their function within a tumour context is not as well known and is controversial. They could have a tolerogenic role towards tumour cells in the absence of an activator but they also have the capacity to become activated in response to Toll-like receptor (TLR) ligands and could therefore be useful for therapeutic purposes. PMID:19850548
Charles, Julie; Chaperot, Laurence; Salameire, Dimitri; Di Domizio, Jérémy; Aspord, Caroline; Gressin, Rémy; Jacob, Marie-Christine; Richard, Marie-Jeanne; Beani, Jean-Claude; Plumas, Joel; Leccia, Marie-Thérčse
In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4+HLA-DR+, CD8+ T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-?/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.
Duarte, Mariana Costa; Araujo, Marcelo Grossi; Campi-Azevedo, Ana Carolina; Teixeira-Carvalho, Andrea; Peruhype-Magalhaes, Vanessa; Trindade, Bruno Caetano; dos Santos Dias, Raquel; Martins, Marina Lobato; Carneiro-Proietti, Anna Barbara de Freitas; Guedes, Antonio Carlos; Goncalves, Denise Utsch; Martins-Filho, Olindo Assis
Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29?423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996; 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis.
Vajdic, Claire M.; Falster, Michael; Engels, Eric A.; Martinez-Maza, Otoniel; Turner, Jennifer; Hjalgrim, Henrik; Vineis, Paolo; Seniori Costantini, Adele; Bracci, Paige M.; Holly, Elizabeth A.; Willett, Eleanor; Spinelli, John J.; La Vecchia, Carlo; Zheng, Tongzhang; Becker, Nikolaus; De Sanjose, Silvia; Chiu, Brian C.-H.; Dal Maso, Luigino; Cocco, Pierluigi; Maynadie, Marc; Foretova, Lenka; Staines, Anthony; Brennan, Paul; Davis, Scott; Severson, Richard; Cerhan, James R.; Breen, Elizabeth C.; Birmann, Brenda; Grulich, Andrew E.; Cozen, Wendy
Uveitis is a complex multifactorial autoimmune disease of the eye characterized by inflammation of the uvea and retina, degen- eration of the retina, and blindness in genetically predisposed patients. Using the rat model of experimental autoimmune uveitis (EAU), we previously identified three quantitative trait loci (QTL) associated with EAU on rat chromosomes 4, 12, and 10 (Eau1, Eau2, and Eau3).
Mary J. Mattapallil; Azize Sahin; Phyllis B. Silver; Shu-Hui Sun; Chi-Chao Chan; Elaine F. Remmers; J. Fielding Hejtmancik; Rachel R. Caspi
Lymphocyte trafficking is a key step in the pathogenesis of various autoimmune diseases. Recruitment of autoreactive lymphocytes to inflamed tissues is a defining feature of numerous persistent organ-specific autoimmune conditions and various therapies are now used in several of these diseases which appear to specifically block lymphocyte migration. Thus, better understanding of the molecular events involved in homing of autoreactive pathogenic lymphocytes may present novel opportunities for pharmacological intervention in autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, type-1 diabetes and psoriasis. This review describes recent progress in understanding lymphocyte trafficking in autoimmunity, focusing on the involvement of the chemokine and chemokine receptor superfamily. Possible strategies to improve therapeutics for autoimmune diseases arising from these studies are discussed. PMID:24164387
Comerford, Iain; Kara, Ervin E; McKenzie, Duncan R; McColl, Shaun R
To improve the efficacy of immunotherapy for cancer and autoimmune diseases, recent ongoing and completed clinical trials have focused on specific targets to redirect the immune network toward eradicating a variety of tumors and ameliorating the self-destructive process. In a previous review, both systemic immunomodulators and monoclonal antibodies (mAbs), anti-CTLA-4, and anti-CD52, were discussed regarding therapeutics and autoimmune sequelae, as well as predisposing factors known to exacerbate immune-related adverse events (irAEs). This review will focus on immune-checkpoint inhibitors, and the data from most clinical trials involve blockade with anti-CTLA-4 such as ipilimumab. However, despite the mild to severe irAEs observed with ipilimumab in ~60% of patients, overall survival (OS) averaged ~22–25% at 3–5?years. To boost OS, other mAbs targeting programed death-1 and its ligand are undergoing clinical trials as monotherapy or dual therapy with anti-CTLA-4. Therapeutic combinations may generate different spectrum of opportunistic autoimmune disorders. To simulate clinical scenarios, we have applied regulatory T cell perturbation to murine models combined to examine the balance between thyroid autoimmunity and tumor-specific immunity.
Kong, Yi-chi M.; Flynn, Jeffrey C.
It is believed that in utero environmental factors contribute to autism spectrum disorder (ASD). The goal of this study was to demonstrate, using the largest cohort reported so far, that mothers of an ASD child have an elevated frequency of anti-brain antibodies and to assess whether brain reactivity is associated with an autoimmune diathesis of the mother. We screened plasma of 2431 mothers of an ASD child from Simon Simplex Collection and plasma of 653 unselected women of child-bearing age for anti-brain antibodies using immunohistology on mouse brain. Positive and negative plasma from mothers with an ASD child were analyzed for anti-nuclear antibodies and for autoimmune disorders. Mothers of an ASD child were four times more likely to harbor anti-brain antibodies than unselected women of child-bearing age (10.5 vs 2.6%). A second cohort from The Autism Genetic Resource Exchange with multiplex families displayed an 8.8% prevalence of anti-brain antibodies in the mothers of these families. Fifty-three percent of these mothers with anti-brain antibodies also exhibited anti-nuclear autoantibodies compared with 13.4% of mothers of an ASD child without anti-brain antibodies and 15% of control women of child-bearing age. The analysis of ASD mothers with brain-reactive antibodies also revealed an increased prevalence of autoimmune diseases, especially rheumatoid arthritis and systemic lupus erythematosus. This study provides robust evidence that brain-reactive antibodies are increased in mothers of an ASD child and may be associated with autoimmunity. The current study serves as a benchmark and justification for studying the potential pathogenicity of these antibodies on the developing brain. The detailed characterization of the specificity of these antibodies will provide practical benefits for the management and prevention of this disorder. PMID:23958959
Brimberg, L; Sadiq, A; Gregersen, P K; Diamond, B
This study was purpose to investigate the clinical characteristics of B-cell chronic lymphoproliferative disorders (B-CLPD) complicated by autoimmune hemolytic anemia (AIHA) so as to improve the understanding of this disease. The clinical characteristics, laboratory data, therapy and outcome of 14 patients suffering from B-CLPD complicated by AIHA were retrospectively analyzed in Wuxi People Hospital and the First Affiliated Hospital of Nanjing Medical University from 2000 to 2012. The results showed that 9 cases of the 14 patients were patients with chronic lymphocytic leukemia (CLL), 5 cases were patients with lymphoma, at time of hemolysis the median level of hemoglobin was 61 (33 - 84)g/L, the median ratio of reticulocytes was 12.0 (3.1 - 35.0)%, the positive rate of Coombs test was 100%. 1 case received corticosteroid alone, 5 cases were treated with chemotherapy combined with corticosteroid, 8 cases were treated with immunochemotherapy rituximab combined with corticosteroid. Overall response rate was 100%, in which CR was 78.6% (11/14), PR was 21.4% (3/14). The follow-up for these patients were performed to now, 35.7% (5/14) patients relapsed with hemolysis again, but they showed therapeutic response to treatment with above-mentioned therapy. From patients treated with rituximab alone, only 1 patient relapsed. Among 14 patients, 6 cases died, 1 case was lost, the other cases are still alive. It is concluded that the AIHA is the commonest complication of B-CLPD, it can be observed at different stages of B-CLPD, the treatment with corticosteroids can give well therapeutic effect for these patients, but the long time CR is lower, the rituximab has been confirmed to be effective for B-CLPD complicated by AIHA. PMID:23815912
Zhuang, Yun; Fan, Lei; Shen, Yun-Feng; Xu, Wei; Li, Jian-Yong
Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I
M. F. McCarty
Cytokines play a major role in the innate and the adaptive immune responses. Since cytokines are very powerful messengers, several regulatory systems (in all levels: production, secretion, effect on target) control their action in order to prevent overstimulation of cytokines. Recently, a negative feedback of cytokine activity in the target cell, namely suppressor of cytokine signaling (SOCS) was defined. This regulatory system consist of 8 proteins (CIS.SOCS 1-7) n which each one of them specifically regulates one or more cytokines. Malfunction of the SOCS proteins may lead to unregulated activity of cytokines which may lead to the development of allergic and autoimmune disorders. PMID:24167931
Mahlab-Guri, Keren; Asher, Ilan; Sthoeger, Zev
Background: Activation of the type I interferon (IFN) pathway has been implicated in the pathogenesis of systemic autoimmune disorders but its role in the pathogenesis of organ-specific autoimmunity is limited. We tested the hypothesis that endogenous expression of type I IFN functional activity contributes to the pathogenesis of autoimmune thyroid disease (ATD) and type I diabetes (T1DM). Methods: We studied 39 patients with ATD and 39 age and sex matched controls along with 88 T1DM patients and 46 healthy matched controls respectively. Available clinical and serological parameters were recorded by chart review, and thyroid ultrasound was performed in 17 ATD patients. Type I IFN serum activity was determined in all subjects using a reporter cell assay. The rs1990760 SNP of the interferon-induced helicase 1 gene was genotyped in ATD patients. Results: Serum type I IFN activity was increased in patients with ATD and T1DM compared to controls (p-values: 0.002 and 0.04, respectively). ATD patients with high type I IFN serum activity had increased prevalence of antibodies against thyroglobulin (anti-Tg) and cardiopulmonary manifestations compared to those with low IFN activity. Additionally, the presence of micronodules on thyroid ultrasound was associated with higher type I IFN levels. In patients with T1DM, high IFN levels were associated with increased apolipoprotein-B levels. Conclusion: Serum type I IFN activity is increased in ATD and T1DM and is associated with specific clinical, serological, and imaging features. These findings may implicate type I IFN pathway in the pathogenesis of specific features of organ-specific autoimmunity.
Mavragani, Clio P.; Niewold, Timothy B.; Chatzigeorgiou, Antonis; Danielides, Stamatina; Thomas, Dimitrios; Kirou, Kyriakos A.; Kamper, Elli; Kaltsas, Grigorios; Crow, Mary K.
Celiac disease is a common autoimmune disorder characterized by an intestinal inflammation triggered by gluten, a storage protein found in wheat, rye and barley. Similar to other autoimmune diseases such as type 1 diabetes, psoriasis and rheumatoid arthritis, celiac disease is the result of an immune response to self-antigens leading to tissue destruction and production of autoantibodies. Common diseases like celiac disease have a complex pattern of inheritance with inputs from both environmental as well as additive and non-additive genetic factors. In the past few years, Genome Wide Association Studies (GWAS) have been successful in finding genetic risk variants behind many common diseases and traits. To complement and add to the previous findings, we performed a GWAS including 206 trios from 97 nuclear Swedish and Norwegian families affected with celiac disease. By stratifying for HLA-DQ, we identified a new genome-wide significant risk locus covering the DUSP10 gene. To further investigate the associations from the GWAS we performed pathway analyses and two-locus interaction analyses. These analyses showed an over-representation of genes involved in type 2 diabetes and identified a set of candidate mechanisms and genes of which some were selected for mRNA expression analysis using small intestinal biopsies from 98 patients. Several genes were expressed differently in the small intestinal mucosa from patients with celiac autoimmunity compared to intestinal mucosa from control patients. From top-scoring regions we identified susceptibility genes in several categories: 1) polarity and epithelial cell functionality; 2) intestinal smooth muscle; 3) growth and energy homeostasis, including proline and glutamine metabolism; and finally 4) innate and adaptive immune system. These genes and pathways, including specific functions of DUSP10, together reveal a new potential biological mechanism that could influence the genesis of celiac disease, and possibly also other chronic disorders with an inflammatory component. PMID:23936387
Östensson, Malin; Montén, Caroline; Bacelis, Jonas; Gudjonsdottir, Audur H; Adamovic, Svetlana; Ek, Johan; Ascher, Henry; Pollak, Elisabet; Arnell, Henrik; Browaldh, Lars; Agardh, Daniel; Wahlström, Jan; Nilsson, Staffan; Torinsson-Naluai, Ĺsa
Celiac disease is a common autoimmune disorder characterized by an intestinal inflammation triggered by gluten, a storage protein found in wheat, rye and barley. Similar to other autoimmune diseases such as type 1 diabetes, psoriasis and rheumatoid arthritis, celiac disease is the result of an immune response to self-antigens leading to tissue destruction and production of autoantibodies. Common diseases like celiac disease have a complex pattern of inheritance with inputs from both environmental as well as additive and non-additive genetic factors. In the past few years, Genome Wide Association Studies (GWAS) have been successful in finding genetic risk variants behind many common diseases and traits. To complement and add to the previous findings, we performed a GWAS including 206 trios from 97 nuclear Swedish and Norwegian families affected with celiac disease. By stratifying for HLA-DQ, we identified a new genome-wide significant risk locus covering the DUSP10 gene. To further investigate the associations from the GWAS we performed pathway analyses and two-locus interaction analyses. These analyses showed an over-representation of genes involved in type 2 diabetes and identified a set of candidate mechanisms and genes of which some were selected for mRNA expression analysis using small intestinal biopsies from 98 patients. Several genes were expressed differently in the small intestinal mucosa from patients with celiac autoimmunity compared to intestinal mucosa from control patients. From top-scoring regions we identified susceptibility genes in several categories: 1) polarity and epithelial cell functionality; 2) intestinal smooth muscle; 3) growth and energy homeostasis, including proline and glutamine metabolism; and finally 4) innate and adaptive immune system. These genes and pathways, including specific functions of DUSP10, together reveal a new potential biological mechanism that could influence the genesis of celiac disease, and possibly also other chronic disorders with an inflammatory component.
Ostensson, Malin; Monten, Caroline; Bacelis, Jonas; Gudjonsdottir, Audur H.; Adamovic, Svetlana; Ek, Johan; Ascher, Henry; Pollak, Elisabet; Arnell, Henrik; Browaldh, Lars; Agardh, Daniel; Wahlstrom, Jan; Nilsson, Staffan; Torinsson-Naluai, Asa
Autoreactive T cells exist in healthy individuals and represent a potential reservoir of pathogenic effectors which, when stimulated by microbial adjuvants, could trigger an autoimmune disease. Experimental studies have indicated that xenobiotics, well defined from a chemical point of view, could promote the differentiation of autoreactive T cells towards a pathogenic pathway. It is therefore theoretically possible that compounds present
Gilbert J. Fournie; Magali Mas; Bastien Cautain; Magali Savignac; Jean-François Subra; Lucette Pelletier; Abdelhadi Saoudi; Dominique Lagrange; Maryline Calise; Philippe Druet
Celiac disease (CD) has a multifactorial etiology with complex genetics and frequently occurs in association with other autoimmune disorders. Even though triggered by a dietary antigen, it shows many autoimmune features, the most peculiar being the presence of high titers of anti-tissue transglutaminase 2 autoantibodies, produced in the small intestinal mucosa since the early stages of the disease. More than 60% of CD-associated susceptibility loci are shared with at least another autoimmune condition, suggesting common pathogenic mechanisms. In particular, recognition of peptides by HLA molecules, posttranslational modifications required for optimal peptide binding and immune mechanisms leading to tissue damage have been found in CD as well as in other autoimmune diseases. This review briefly summarizes the main autoimmune features of CD, underlining the similarities with other autoimmune disorders, in particular with type 1 diabetes mellitus. Furthermore, the role of gluten and microbiome in driving autoimmunity is discussed. PMID:24979198
Troncone, Riccardo; Discepolo, Valentina
This review of human autoimmune thyroid disease (AITD) focuses mainly on the epidemiology and pathophysiology of this very common disorder, although some specific clinical situations are discussed. One peculiarity of AITD is the existence of two contrasting phenotypes: hypothyroid thyroiditis and hyperthyroid Graves' disease. Graves' disease is characterized by the presence of anti-TSH receptor antibodies capable of activating the TSH receptor, leading to thyroid hypertrophy and hyperfunction. In contrast, autoimmune thyroiditis progresses slowly, through necrosis/apoptosis of thyroid cells and their functional impairment. Other forms of autoimmune thyroiditis such as postpartum thyroiditis and silent thyroiditis are also described. The aim of this non exhaustive review is to provide the interested reader with basic information required for further investigation. PMID:24672979
The higher prevalence of autoimmune diseases in women compared to men could be due to effects of ovarian hormones, pregnancy and/or the presence of a 2nd X chromosome. To elucidate the role of these factors, we investigated the prevalence and spectrum of autoimmune diagnoses in women with primary ovarian insufficiency associated with X chromosome monosomy (Turner syndrome, TS, n=244) and women with karyotypically normal (46,XX) primary ovarian insufficiency (POI, n=457) in a prospective study, conducted at the National Institutes of Health. We compared the study group prevalence to normative data for the U.S. population of women. Chronic lymphocytic (Hashimoto’s) thyroiditis (HT) occurred in 37% of women with TS vs. 15% with POI (P<0.0001); HT prevalence in both ovarian insufficiency groups significantly exceeded that in U.S. population of women (5.8%). Inflammatory bowel (IBD, 4%) and celiac disease (CD, 2.7%) were significantly increased in TS, but not in POI. No other autoimmune diagnosis, including Graves’ disease or Type 1 diabetes appears to be significantly increased in either group. Women with TS had higher pro-inflammatory IL6 and TGF ?1 levels (p<0.0001 for both), and lower anti-inflammatory IL10 and TGF ?2 levels (p<0.005 for both) compared to POI and to normal volunteers. Lifetime estrogen exposure and parity were significantly lower in TS compared to POI, which were in turn lower than the general population of women. The finding that lymphocytic thyroiditis is greatly increased in both women with TS and POI suggests that factors associated with ovarian insufficiency per se promote this form of autoimmunity. The absence of a normal second X-chromosome further contributes to increased autoimmunity in TS.
Bakalov, Vladimir K.; Gutin, Liat; Cheng, Clara M; Zhou, Jian; Sheth, Puja; Shah, Kavita; Arepalli, Sruthi; Vanderhoof, Vien; Nelson, Lawrence M.; Bondy, Carolyn A.
After a brief summary on the properties of the Epstein–Barr virus (EBV), the course and latency stages of the infection, the characteristics of infectious mononucleosis (IM), and other disorders caused by this virus, as well as the course of the serological responses to EBV, the current paper focuses on the role of EBV in two autoimmune disorders: multiple sclerosis (MS), and systemic lupus erythematosus (SLE). Diverse evidence suggests that infection by EBV during late childhood or young adulthood may have a role in the pathogenesis of MS. These include the similarity between the geographical distribution of IMand MS, the high risk of contracting MS by individuals who have recovered from IM, the elevation of the titers of IgG antibodies against EBV nuclear antigens occurring years before the initial manifestations of MS, and the extremely rare occurrence of MS in individuals seronegative for EBV. However, the data on the mechanism underlying the relationship between EBV and MS are controversial. Moreover, many observations indicate that EBV contributes also to the pathomechanism of SLE. However, this contribution differs from the relationship between EBV and MS, as shown by the lack of any increase in the risk of SLE after IM. In SLE, EBV serology is quantitatively and qualitatively different from the normal response – that is, EBV viral load is higher and a strong cross-reaction can be detected between certain EBV antigens and autoantigens of pathological importance. These observations, along with the findings pointing to a possible role of EBV in rheumatoid arthritis and myasthenia gravis indicate that infection by EBV may be one of the environmental factors, which can facilitate the development of some autoimmune disorders in genetically susceptible individuals.
Background Soluble CD200 (sCD200) is a novel immuno-effective molecule, which acts to regulate inflammatory and acquired immune responses. Recently, our study group showed that sCD200 was present in serum and blister fluid in a patient with bullous pemphigoid and a patient with toxic epidermal necrolysis. We therefore planned this study to evaluate the sCD200 levels of autoimmune and inflammatory skin disorder patients and to compare them with that of healthy controls. Maleral/Methods Our study included 30 consecutive patients with psoriasis vulgaris, 15 with pemphigus vulgaris, and 15 healthy controls. Clinical examination and laboratory tests were performed on the same day. Psoriasis patients were also assessed with the Psoriasis Area and Severity Index (PASI) and pemphigus patients were assessed using the Pemphigus Disease Area Index (PDAI). Levels of sCD200 in the serum samples were quantified using ELISA kits. Results The serum sCD200 level was observed to be statistically significantly higher in patients with psoriasis vulgaris (96.7±15.8) compared to patients with pemphigus vulgaris (76.2±14.6), (p<0.001) and healthy controls (26.8±7.0) (p<0.001). The serum sCD200 levels were observed to be statistically significantly higher in patients with pemphigus vulgaris compared with that in healthy controls (p<0.001). In addition, there was a statistically significant correlation between serum sCD200 levels and PDAI (r=0.987, p=0.001). Nevertheless, there was no statistically significant correlation between serum sCD200 levels and PASI (r=0.154, p=0.407). Conclusions sCD200 might play a role in immune response in the pathogenesis of autoimmune and inflammatory skin disorders. However, it remains to be fully elucidated how sCD200 can orchestrate inflammatory response in psoriasis and pemphigus.
Akman-Karakas, Ayse; Yalcin, Arzu Didem; Koc, Saliha; Gumuslu, Saadet; Senol, Yesim Yigiter; Ozkesici, Birgul; Genc, Gizem Esra; Ergun, Erkan; Ongut, Gozde; Yilmaz, Ertan; Uzun, Soner; Alpsoy, Erkan
B cell-directed therapies are promising treatments for autoimmune disorders. Besides targeting CD20, newer B cell-directed therapies are in development that target other B cell surface molecules and differentiation factors. An increasing number of B cell-directed therapies are in development for the treatment of autoimmune disorders. Like rituximab, which is approved as a treatment for rheumatoid arthritis (RA), many of these newer agents deplete B cells or target pathways essential for B cell development and function; however, many questions remain about their optimal use in the clinic and about the role of B cells in disease pathogenesis. Other therapies besides rituximab that target CD20 are the furthest along in development. Besides targeting CD20, the newer B cell-directed therapies target CD22, CD19, CD40–CD40L, B cell activating factor belonging to the TNF family (BAFF) and A proliferation-inducing ligand (APRIL). Rituximab is being tested in an ever-increasing number of autoimmune disorders and clinical studies of rituximab combined with other biological therapies are being pursued for the treatment of rheumatoid arthritis (RA). B cell-directed therapies are being tested in clinical trials for a variety of autoimmune disorders including RA, systemic lupus erythematosus (SLE), Sjögren's syndrome, vasculitis, multiple sclerosis (MS), Graves' disease, idiopathic thrombocytopenia (ITP), the inflammatory myopathies (dermatomyositis and polymyositis) and the blistering skin diseases pemphigus and bullous pemphigoid. Despite the plethora of clinical studies related to B cell-directed therapies and wealth of new information from these trials, much still remains to be discovered about the pathophysiological role of B cells in autoimmune disorders.
Levesque, M C
The rational way to set a diagnosis and estimate a prognosis in rheumatology is to start by setting a tentative diagnosis and then follow a fixed scheme for laboratory testing, eg, by using an agreed algorithm. The use of order algorithms can be extended to post-test algorithms that will assist clinicians in approaching the right diagnosis and prognosis. New methods used in autoimmune serology do not deliver results that can be directly compared to those of older methods, and thus the new methods need to be thoroughly tested with sera from differential diagnostically relevant disease controls to set a clinically meaningful cut-off for positivity. Borderline positive results need to be treated with special care to avoid misuse. Early diagnosis is of great importance, and serological results can be very useful if used the right way. European efforts to secure rational diagnostic work-up in autoimmune rheumatic disease have led to a better dialogue between clinicians and laboratory scientists in several countries. PMID:16898171
Wiik, A; Cervera, R; Haass, M; Kallenberg, C; Khamashta, M; Meroni, P L; Piette, J-C; Schmitt, R; Shoenfeld, Y
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
Giorgina Mieli-Vergani; Diego Vergani
Autoimmune inner ear disease probably accounts for less than 1% of all cases of balance disorders, but its incidence is often\\u000a overlooked due to the absence of a specific diagnostic test. Furthermore, in several systemic autoimmune diseases the vestibulo-cochlear\\u000a system may be affected. Clinical features comprise generalized imbalance, ataxia, motion intolerance, episodic vertigo and\\u000a positional vertigo. An autoimmune mechanism seems
Roberto Bovo; Andrea Ciorba; Alessandro Martini
Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders.
In a retrospective cohort of more than 4 million white and black male United States (US) veterans, we explored the role of specific prior autoimmune, infectious, inflammatory, and allergic disorders in the etiology of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Patients were selected from computerized inpatient discharge records at US Veterans Affairs hospitals. The analysis included 4641 patients (3040 white, 1601 black) and 2046 patients (1312 white; 734 black) with a discharge diagnosis of MM and MGUS, respectively. Using Poisson regression, we calculated age-adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the relationship between MM, MGUS, and specific prior medical conditions. Significantly elevated risks of MM were associated with broad categories of autoimmune (RR, 1.15; 95% CI, 1.02-1.28), infectious (RR, 1.29; 95% CI, 1.20-1.38), and inflammatory disorders (RR, 1.18; 95% CI, 1.10-1.27) and specific prior autoimmune (polymyositis/dermatomyositis, systemic sclerosis, autoimmune hemolytic anemia, pernicious anemia, and ankylosing spondylitis), infectious (pneumonia, hepatitis, meningitis, septicemia, herpes zoster, and poliomyelitis), and inflammatory (glomerulonephritis, nephrotic syndrome, and osteoarthritis) disorders. Risks for MGUS were generally of similar magnitude. Our results indicate that various types of immune-mediated conditions might act as triggers for MM/MGUS development. PMID:18239085
Brown, Linda Morris; Gridley, Gloria; Check, David; Landgren, Ola
Nonsegmental vitiligo is a depigmented skin disorder showing acquired, progressive, and depigmented lesions of the skin, mucosa, and hair. It is believed to be caused mainly by the autoimmune loss of melanocytes from the involved areas. It is frequently associated with other autoimmune diseases, particularly autoimmune thyroid diseases including Hashimoto's thyroiditis and Graves' disease, rheumatoid arthritis, type 1 diabetes, psoriasis, pernicious anemia, systemic lupus erythematosus, Addison's disease, and alopecia areata. This indicates the presence of genetically determined susceptibility to not only vitiligo but also to other autoimmune disorders. Here, we summarize current understanding of autoimmune pathogenesis in non-segmental vitiligo. PMID:21804820
Oiso, Naoki; Suzuki, Tamio; Fukai, Kazuyoshi; Katayama, Ichiro; Kawada, Akira
ABSTRACT The co-occurrence of autoimmune diseases has been epidemiologically studied and has aided in our understanding of autoimmunity. The combination of at least three autoimmune diseases in the same patient has defined as multiple autoimmune syndrome (MAS). About 25 percent of patients with autoimmune diseases have a tendency to develop additional autoimmune diseases. MAS is recognized with increasing frequency. Several associations have been proposed as a form of MAS. Multiple autoimmune syndrome can be classified into three groups according to the prevalence of their associations with one another: type 1, type 2 and type 3. Genetic, infectious, immunologic and psychological factors have all been implicated in the development of MAS. In MAS, patients often have at least one dermatological condition, usually vitiligo or alopecia areata. The pathogenesis of multiple autoimmune disorders is not known yet, perhaps environmental triggers and genetic susceptibility are involved. Abnormalities of both humoral and cell-mediated immunity have been described. However, as new perspectives develop on the pathogenesis and natural history of autoimmune diseases, a refinement in the methodology for the study of the co-occurrence of disease is warranted in order to maximize the information that one may realize from such studies. This paper presents some recent results of studies in light of current understanding of the natural history of autoimmune diseases.
COJOCARU, M; COJOCARU, Inimioara Mihaela; SILOSI, Isabela
Cytokines are critical coordinators of the immune response necessary for resolving bacterial and viral assaults on the immune system. In particular, the IL-12 family of cytokines are key players in the regulation of T cell responses. These responses are orchestrated by monocytes, macrophages, and dendritic cells which produce the members of the IL-12 family of cytokines in response to infection. IL-27 and IL-23 are two cytokines that are related to IL-12; these cytokines share homology at the subunit, receptor, and signalling levels. IL-12 is composed of p35 and p40 subunits, which, when combined together form the bioactive IL-12p70. IL-23 is composed of the IL-12p40 subunit as well as the IL-23p19 subunit, which shares homology with IL-12p35. IL-27 is composed of EBI3 and p28. These three cytokines activate similar members of the JAK/STAT signalling pathways as a result of homology in their receptor components. Production of these cytokines by activated monocytes, macrophages, and dendritic cells results in the activation and differentiation of T cells. In spite of their similarity, each of these cytokines has specific roles in the regulation of immune responses. IL-12 is required for the induction of IFN-gamma production, critical for the induction of Th1 cells. IL-27 has been shown to play a role in the induction of Th1 cells from naive T cells, whereas IL-23 has been demonstrated to play a key role in the induction of the newly described Th17 cells. Recently, a novel heterodimeric and anti-inflammatory cytokine composed of the IL-12p35 and EBI3 subunits has been identified as IL-35. The biological properties of the IL-12 family of cytokines, the signalling pathways mediated by these cytokines and their role in infection, inflammation, and autoimmune diseases will be the focus of this review. PMID:19275692
Gee, Katrina; Guzzo, Christina; Che Mat, Nor Fazila; Ma, Wei; Kumar, Ashok
Background In children presenting with obsessive compulsive disorder (OCD) and/or tics, especially those with a temporal association with streptococcal pharyngitis (e.g., PANDAS; Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus), there is speculation about whether tonsillectomy/adenoidectomy might improve the child’s neuropsychiatric course. Our objective was to examine whether removal of tonsils and/or adenoids impacted streptococcal antibody titers, the timing of onset of OCD and/or tics, and the clinical severity of these symptoms. Methods Study participants (n=112; average age=9.2 ± 2.4; 44 female) were recruited as part of a prospective investigation of neuropsychiatric phenomena with temporal association to streptococcal pharyngitis and examined by family history, diagnostic interview, physical examination, medical record review, psychological testing, and streptococcal antibodies and divided into surgical or non-surgery groups. The surgical group consisted of children having previously had a tonsillectomy and/or adenoidectomy (n=32). The remaining children were categorized as non-surgery (N=76). Measures of OCD and tic severity, streptococcal antibody titers, and PANDAS classification were compared between both groups. Results There were no significant differences as determined by streptococcal antibody titers, PANDAS classification, and OCD or tic severity between the surgical and non-surgery groups. Most participants had surgery before onset of neuropsychiatric symptoms and surgery did not affect symptomology. Conclusions Streptococcal antibodies and neuropsychiatric symptom severity did not differ on the basis of surgical status. From these data we cannot support that tonsillectomy and adenoidectomy are likely to impact positively the course of OCD/tics or streptococcal antibody concentrations.
Murphy, Tanya K.; Lewin, Adam B.; Parker-Athill, E. Carla; Storch, Eric A.; Mutch, P. Jane
Autoimmune thyropathies are frequent in patients with type 1 diabetes mellitus. Some recently published papers confirm similarly high prevalence of autoimmune thyropathies also in patients with type 2 diabetes mellitus. Chronic autoimmune thyroiditis is the most frequent form of autoimmune thyropathies. Authors examined 79 accidentally selected diabetics (38 women and 41 men, x = 55.4 +/- 2.8). Diabetic patients were divided into three groups. 20 patients with type 1 diabetes mellitus - classical form were the first group, 12 patients with LADA were the second group and 47 patients with type 2 diabetes mellitus constituted the third group. Authors diagnosed chronic autoimmune thyroiditis in 8 (40 %) patients in the group of patients with type 1 diabetes mellitus, in 6 (50%) in the group of patients with LADA and in 20 (43%) of patients with type 2 diabetes mellitus. They didn't find out statistically more frequent prevalence of chronic autoimmune thyroiditis in all groups of patients with diabetes (patients with type 1 diabetes mellitus, patients with LADA, patients with type 2 diabetes mellitus) in comparison with control group of non-diabetic subjects. They found out statistically significant more frequent prevalence of chronic autoimmune thyroiditis in diabetics of woman gender and in diabetics with positive family history of thyropathies. Results of paper confirm recommendation of examining once or twice a year autoantibodies against thyroid gland and level of thyrotropin (TSH) with the aim of early finding of laboratory manifestation of thyroidal autoimmunity or developing functional disorder. PMID:16623276
Schroner, Z; Lazúrová, I; Petrovicová, J
Autoimmune neutropenia (AIN) is a rare entity caused by antibodies directed against neutrophil-specific antigens. It includes primary and secondary autoimmune neutropenia. Acute autoimmune neutropenia can be related to drug-induced mechanism or viral infections. Chronic autoimmune neutropenias occur in the context of autoimmune diseases, hematological malignancies, such as large granular lymphocyte leukemia, primary immune deficiency syndromes or solid tumors. The therapeutic management depends on the etiology. Granulocyte growth factor is the main therapeutic option, raising the question of their long-term utilization safety. Corticosteroids or immunosuppressive therapy are indicated in infection-related AIN or in case of symptomatic autoimmune disease or LGL leukemia. PMID:24680423
Autrel-Moignet, Aline; Lamy, Thierry
Experimental models of autoimmune disease have been used to dissect the mechanisms of disease pathogenesis in the corresponding\\u000a human diseases. This chapter will deal with experimental autoimmune encephalomyelitis (EAE) as a model for human multiple\\u000a sclerosis (MS) and experimental autoimmune diabetes (EAD) in the NOD mouse as a model for human diabetes. In the case of these\\u000a tissue-specific autoimmune diseases,
William J. Karpus
AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems. Since the AhR signaling pathway represents an important link between environmental stimulators and immune-mediated inflammatory disorder, it has become the object of great interest among researchers recently. The current review discusses new insights into the mechanisms of action of a select group of inflammatory autoimmune diseases and the ligand-activated AhR signaling pathway. Representative ligands of AhR, both exogenous and endogenous, are also reviewed relative to their potential use as tools for understanding the role of AhR and as potential therapeutics for the treatment of various inflammatory autoimmune diseases, with a focus on CD4 helper T cells, which play important roles both in self-immune tolerance and in inflammatory autoimmune diseases. Evidence indicating the potential use of these ligands in regulating inflammation in various diseases is highlighted, and potential mechanisms of action causing immune system effects mediated by AhR signaling are also discussed. The current review will contribute to a better understanding of the role of AhR and its signaling pathway in CD4 helper T cell mediated inflammatory disorder. Considering the established importance of AhR in immune regulation and its potential as a therapeutic target, we also think that both further investigation into the molecular mechanisms of immune regulation that are mediated by the ligand-specific AhR signaling pathway, and integrated research and development of new therapeutic drug candidates targeting the AhR signaling pathway should be pursued urgently. PMID:24905409
Zhu, Conghui; Xie, Qunhui; Zhao, Bin
AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems. Since the AhR signaling pathway represents an important link between environmental stimulators and immune-mediated inflammatory disorder, it has become the object of great interest among researchers recently. The current review discusses new insights into the mechanisms of action of a select group of inflammatory autoimmune diseases and the ligand-activated AhR signaling pathway. Representative ligands of AhR, both exogenous and endogenous, are also reviewed relative to their potential use as tools for understanding the role of AhR and as potential therapeutics for the treatment of various inflammatory autoimmune diseases, with a focus on CD4 helper T cells, which play important roles both in self-immune tolerance and in inflammatory autoimmune diseases. Evidence indicating the potential use of these ligands in regulating inflammation in various diseases is highlighted, and potential mechanisms of action causing immune system effects mediated by AhR signaling are also discussed. The current review will contribute to a better understanding of the role of AhR and its signaling pathway in CD4 helper T cell mediated inflammatory disorder. Considering the established importance of AhR in immune regulation and its potential as a therapeutic target, we also think that both further investigation into the molecular mechanisms of immune regulation that are mediated by the ligand-specific AhR signaling pathway, and integrated research and development of new therapeutic drug candidates targeting the AhR signaling pathway should be pursued urgently.
Zhu, Conghui; Xie, Qunhui; Zhao, Bin
Gulf War-related illnesses are mostly common ailments, but with incidence rates that exceed those expected in the population of Gulf War veterans. These illnesses may be the result of combinations of chemical and physiological stressors which may have caused acute cellular effects sufficient to initiate processes of autoimmunity to various organs, tissues or types of cells. Two main suspects in
J. I. Moss
The etiology of autoimmune diseases is multifactorial: genetic, environmental, hormonal, and immunological factors are all considered important in their development. Nevertheless, the onset of at least 50% of autoimmune disorders has been attributed to “unknown trigger factors”. Physical and psychological stress has been implicated in the development of autoimmune disease, since numerous animal and human studies demonstrated the effect of
Ljudmila Stojanovich; Dragomir Marisavljevich
Biermer's disease is an autoimmune atrophic gastritis of the fundus predominantly responsible for a malabsorption of vitamin B12. Despite its association with several autoimmune disorders, few observations have reported an association with autoimmune hemolytic anemia (AIHA). We report a case of Biermer's disease associated with AIHA in a patient of 66 years old. PMID:22796620
Nafil, Hatim; Tazi, Illias; Mahmal, Lahoucine
It is now accepted that there are antibody-mediated diseases of both the peripheral and central nervous systems. Myasthenia gravis remains the prototype autoimmune disease of the neuromuscular junction, but subsequent studies have revealed antibodies to other peripheral and autonomic targets. In the 1990s, antibodies to voltage-gated potassium channel complexes were identified in acquired neuromyotonia, a condition caused by peripheral nerve hyperexcitatibility that leads to muscle fasciulations, muscle cramps and pain. Somewhat surprisingly, the same antibodies were identified in relatively acute-onset central nervous system disorders such as Morvan's syndrome and limbic encephalitis. It turned out that the potassium channel antibodies were mainly directed at other proteins that are complexed with the channels in situ, such as LGI1 and CASPR2. These proteins help localise (CASPR2) and modify (LGI1) potassium channel function, and the antibodies bind to extracellular epitopes and are pathogenic in vitro. Tumours can be found in a proportion of each of these conditions, but the proportion varies from <10% to around 50%. Thymomas are the most common. In 2007, antibodies to NMDA receptors (NR1 principally) were identified and subsequently found quite commonly in younger patients, often women and small children, who have a very complicated form of encephalitis that results in psychiatric and movement disorders. Ovarian teratomas are common in the adult females but rare in children. Other antibodies have now been discovered, each one directed at a specific receptor or ion-channel related associated protein, although so far the associated diseases are fairly rare. Antibodies to glycine receptors are associated with a form of stiff person plus, usually termed progressive encephalomyelitis with rigidity and myoclonus (PERM), a condition which is well described in the literature and can be life threatening. Now it is recognised in more patients with a greater breadth of clinical symptoms. Each of these diseases shows a very good respond to immunotherapies such as steroids, plasma exchange, intravenous immunoglobulins. If the response is poor, second line therapies such as rituximab and/or cylclophosphamide are tried. Some require longer term immunosuppression with azathioprine or mycophenolate. Altogether there is a growing field of immunotherapy-responsive neurological diseases which need to be recognised by the clinicians and treated appropriately. There are now many neurological presentations in which the possibility of an autoimmune disease needs to be considered, and this is beginning to apply to those that are less clearly "organic". PMID:25009325
We briefly survey the concept of autoimmunity and nominate the range of autoimmune diseases that include multisystemic and organ-specific disorders, and cite prevalences of autoimmune diseases in males and females, in humans and in experimental animals. Most human autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and autoimmune thyroid disease, have an increased incidence and prevalence in females, but a few others such as autoimmune diabetes, the Guillain Barré syndrome (GBS) and psoriasis are increased in males. Animal models of autoimmunity show an equivalent sexual dimorphism. The possible reasons for the differing incidence and prevalence of autoimmune diseases in females and males engage our attention. Environmental exposures may differ for females and males. There are innate differences in the function of the female and male immune systems, and there is some evidence for differences between females and males in the ability of a target organ for autoimmunity to withstand damage. In seeking reasons for these differences, we review the role of sex hormones in immunity and include results of trials of hormone therapy in autoimmune diseases. The association of autoimmunity and pregnancy, a female-specific condition, is discussed, and the claimed effects of lymphoid cell microchimerism on provocation of autoimmunity are reviewed. Genetic predisposition is an important factor in autoimmune disease and we particularly focus on genes on the X and Y chromosomes, the role of X chromosome inactivation, and the interaction of the sex of the patient with other genetic factors. The possible role of epigenetic mechanisms, including environmental influences, is then surveyed. We assert that sex is a vital variable that must be considered in all immunological studies, as it should be at all levels of biological research. PMID:19747114
McCombe, P A; Greer, J M; Mackay, I R
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.
Masood, Sadia; Sajid, Sara; Jafferani, Asif; Tabassum, Saadia; Ansar, Sobia
The retinoic acid receptor-related orphan receptor (ROR) subfamily of nuclear receptors are transcription factors involved in the maintenance of circadian rhythm and are essential for proper immune function. The T cell-specific isoform, ROR?t, is required for T helper 17 cells (TH17) development and it has been implicated in the pathogenesis of autoimmune diseases including multiple sclerosis and rheumatoid arthritis. Thus, pharmacological repression of ROR?t may provide a strategy for therapeutic intervention in autoimmune disorders. This chapter provides a summary of the current status for target validation and development of new chemical entities targeting ROR?t. PMID:24728598
Chang, Mi Ra; Rosen, Hugh; Griffin, Patrick R
Autoimmune liver diseases encompass autoimmune hepatitis, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) as lesions of the biliary tract. The term autoimmune cholangitis has not been generally accepted, so it remains an entitiy waiting for precise definition. AIH is a chronic progressive necroinflammatory liver disease mostly occuring in female individuals and leading to ultimate autodestruction of the liver if not treated. Histopathology of the liver reflects the gerneral understanding of the underlying immune especially self reactive CD4 + T-helper cells mediated mechanisms in destruction of liver cells displaying a typical but by no means pathognomonic histopathological pattern. Since there are no specific and generally valid tests the diagnosis should be confirmed by a scoring system including histopathology. Variants of autoimmune hepatitis cover seronegative cases, acute onset autoimmune hepatitis and autoimmune hepatitis with centrilobular necrosis. Differential diagnosis of autoimmune hepatitis includes drug induced chronic hepatitis that may mimick autoimmune hepatitis by clinical course and serology. Histopathology may give helpful hints for the correct diagnosis. Autoimmune lesions of the biliary tract are PBC in the first line. The target antigen of the autoimmune response has been identified, natural history of the diseases is well known and histopathology is pathognomonic in about a third of the cases. In clinical practice liver biopsy is taken to exclude other etiologies when AMA is present in the serum, staging the disease at first diagnosis and to establish diagnosis in cases of AMA negativity. The autoimmune nature of PSC has been discussed in the literature ever since the first description and the answer in not settled yet. Histopathology is relevant for the diagnosis in excluding other etiologies and confirming the diagnosis of small duct PSC. The term autoimmune cholangitis has been used to designate AMA-negative PBC, however, based on research experience and the clinical data it should be reserved to the overlap syndrome of AIH and PSC in children that seem to make up a disease entitiy of its own. PMID:18035685
Dienes, H P
Autoimmune thyroid diseases (ATD), as the most common organ?specific autoimmune disorder, is frequently accompanied by other organ- and nonorgan?specific autoimmune diseases. Although the exact pathogenic mechanism of the coexistence of autoimmune disorders has not been clearly defined, genetic and environmental factors, immune defects, and hormonal changes, may play a key role in polyautoimmunity. The role of human leukocyte antigen (HLA) haplotypes, HLA-B8 and -DR3, in the overlapping of autoimmune disorders was well supported by higher frequency of these haplotypes in primary Sjögren's syndrome (PSS) and ATD. In addition, polymorphisms of the cytotoxic T lymphocytic antigen 4 gene have been reported to be associated with many autoimmune disorders especially those coexisting with ATD. Definite noncasual association of ATD has been clearly documented in patients with PSS, rheumatoid arthritis, and systemic lupus erythematosus. Possible association with ATD is also considered in systemic sclerosis and dermatomyositis. Many authors documented a significantly higher prevalence of antinuclear antibodies (ANAs) in ATD patients in comparison with controls; however, the clinical significance of ANAs in this group is still unknown. The presence of other non?organ?specific antibodies has not been convincingly demonstrated. On the other hand, the prevalence of antithyroid antibodies as well as ATD is higher in patients with systemic connective tissue disease compared with the general population. Basedon these data, there is no evidence for the utility of ANA testing in patients with ATD, but because of the high prevalence of ATD and antithyroid autoantibodies, it is clinically important to screen patients with autoimmune rheumatic disorders for the presence of thyroid autoimmunity. PMID:23222800
Lazúrová, Ivica; Benhatchi, Karim
Many biologic agents that were first approved for the treatment of malignancies are now being actively investigated and used in a variety of autoimmune diseases such as rheumatoid arthritis (RA), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, systemic lupus erythematosus (SLE), and Sjogren’s syndrome. The relatively recent advance of selective immune targeting has significantly changed the management of autoimmune disorders, and in part, can be attributed to the progress made in understanding effector cell function and their signaling pathways. In this review, we will discuss the recent FDA approved biologic therapies that directly target immune cells as well as the most promising investigational drugs affecting immune cell function and signaling for the treatment of autoimmune disease.
Rogers, Jennifer L.; Serafin, Donald S.; Timoshchenko, Roman G.; Tarrant, Teresa K.
Chronic urticaria is defined as hives, typically occurring daily, for greater than 6 weeks duration. Chronic idiopathic urticaria, which has no discernable external cause, comprises the majority of cases of chronic urticaria. Over half of all cases of chronic idiopathic urticaria are thought to occur by an autoimmune mechanism, primarily autoantibodies against the high affinity immunoglobulin E (IgE) receptor (Fc?RI). Chronic urticaria is hypothesized to occur because of a predilection in the patient to develop reactions to self. Supporting this hypothesis, a strong association has been found between chronic urticaria and additional autoimmune diseases, such as thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, celiac disease and type 1 diabetes, among others. Herein, we review the associations between chronic urticaria, thyroid disease, and other autoimmune disorders, as well as the implications that these correlations hold for therapeutic intervention in chronic urticaria. PMID:24305753
Fraser, Kathleen; Robertson, Lynne
The present invention provides compositions and methods for preventing and treating gastrointestinal disorders by administering to a subject an effective amount of secretin either alone or in combination with an effective amount of oxytocin. The invention...
M. G. Welch D. A. Ruggiero M. Anwar
... cells, not stem cells from a donor. Systemic Lupus Erythematosus Systemic lupus erythematosus (pronounced sis-TEM-ick LOO-pus AIR- ... the disorder after no other treatment worked: Systemic lupus erythematosus 17 patients Symptoms improved enough for the ...
Progesterone induced dermatitis is a rare disorder. It typically occurs in females due to an autoimmune phenomenon to endogenous progesterone production, but can also be caused by exogenous intake of a synthetic progestin. Here in, we present a case of autoimmune progesterone anaphylaxis (AIPA) observed in an adolescent female. The patient is an 18-year-old Caucasian female with no significant past medical history and no prior exogenous hormone use, who presented to her primary care physician complaining of cyclic skin eruptions with dyspnea, cough and respiratory distress. She noted that her symptoms occurred monthly, just prior to her menses. An intradermal skin test using 0.1 cml of progesterone was performed. The patient developed a 15 mm wheal after 15 minutes, confirming the diagnosis of AIPA. The patient was started on a continuous regimen of an oral conjugated estrogen (0.625 mg). The skin eruptions and respiratory symptoms have not returned since the initiation of this therapy. Autoimmune progesterone dermatitis manifests via the occurrence of cyclic skin eruptions. Women with the disorder commonly present with dermatologic lesions in the luteal phase of the menstrual cycle, if there are any other organ involvement in addition to skin (e.g. lung, GI) the reaction should be called as autoimmune progesterone anaphylaxis. Diagnosis of AIPA is confirmed by performing a skin allergen test using progesterone. PMID:17563411
Bemanian, Mohammad Hassan; Gharagozlou, Mohammad; Farashahi, Mohammad Hossein; Nabavi, Mohammad; Shirkhoda, Zahra
As the last extensive series of patients with Addison's disease and coincident autoimmune phenomena were published approximately two decades ago, we studied the cause of the disease, the prevalence of autoimmune disorders and the frequency of occurrence of autoantibodies in 91 patients (31 men and 60 women, mean age 45.3-years-old, range 12–77) with Addison's disease.The cause of Addison's disease in
Pierre M. J. Zelissen; Egbert J. E. G. Bast; Ronald J. M. Croughs
In vitro lymphocyte function of 13 patients with selective IgA deficiency was studied. IgG, IgA and IgM secretion by pokeweed mitogen-stimulated peripheral blood lymphocytes from normal donors and IgA deficient patients was measured by an enzyme-linked immunosorbent assay. Addition of concanavalin A or hydrocortisone and co-cultures of B and T cell enriched populations from patients and normal donors, allowed us to investigate B cell Ig production and T cell regulatory abnormalities. IgA production by these patients' B cells was either absent or very low, as compared to their total Ig production, even in the presence of optimal T cell help. Several T cell immunoregulatory abnormalities were seen in different patients. A moderate increase in suppressor activity selective for IgA production was observed in some, but does not appear to play a major role in the pathogenesis of the IgA deficiency. In others, with associated autoimmune phenomena, a decrease in suppressor T cell function was found.
De la Concha, E G; Subiza, J L; Fontan, G; Pascual-Salcedo, D; Sequi, J; Bootello, A
Background Turner syndrome is caused by numeric and structural abnormalities of the X chromosome. An increased frequency of autoimmunity as well as an elevated incidence of autoantibodies was observed in Turner patients. The aim of this study was to conduct a retrospective analysis of the incidence of autoimmunity in 66 Italian patients affected by Turner syndrome. Methods Sixty-six unselected and consecutive Italian Turner patients were recruited. The association between age, karyotype and the presence of clinical/pre-clinical autoimmune disorders and of autoantibodies was examined. Results Out of the 66 Turner patients, 26 had thyroid autoimmune disorders (39.4%), 14 patients had Hashimoto’s thyroiditis with clinical or subclinical hypothyroidism (21.2%) and 12 patients had circulating anti-thyroid antibodies, echographic pattern of diffuse hypoechogenicity and normal thyroid hormone levels (18.2%). None were affected by Graves’ disease. We analyzed the overall incidence of thyroid autoimmunity within the 3 different age groups 0–9.9, 10–19.9 and 20–29.9 years. No statistically significant difference was observed in the incidence of thyroid autoimmunity within the age-groups (?2-test p?>?0.05). Out of the 66 patients, 31 patients had the 45,X karyotype; within this first group 14 out of 31 patients were affected by autoimmune thyroid disease. A second group of 29 patients included 19 patients with mosaicism, 5 patients with deletions and 5 patients with ring chromosome; out of these 29 patients 7 were affected by autoimmune thyroid disease. A third group included 6 patients with X isochromosome; 5 out of 6 were affected by autoimmune thyroid disease. A statistically significant difference in the frequency of thyroid autoimmunity within the different karyotype groups was observed (?2-test p?=?0.0173). When comparing the X isochromosome group with the pooled group of other karyotypes, of note, the frequency of thyroid autoimmunity was statistically higher in the X isochromosome group (Fisher exact test p?=?0.0315). Conclusions Our data confirm a high frequency of thyroid autoimmunity in Italian Turner patients. Patients with X isochromosome are more prone to develop thyroid autoimmunity. Further, an early assay of autoantibodies and monitoring thyroid hormones is fundamental for detecting hypothyroidism earlier and start adequate replacement therapy.
This book contains 25 chapters. Some of the chapter titles are: Genetic Predisposition to Autoimmune Diseases; Systemic Lupus Erythematosus; Autoimmune Aspects of Rheumatoid Arthritis; Immunology of Insulin-Dependent Diabetes; and Adrenal Autoimmunity and Autoimmune Polyglandular Syndromes.
Rose, N.R.; Mackay, I.R.
Objectives: To determine the characteristics of adult-onset autoimmune chorea, and compare paraneoplastic and idiopathic subgroups. Methods: Thirty-six adults with autoimmune chorea were identified at Mayo Clinic (Rochester, MN) from 1997 to 2012. Medical record and laboratory data were recorded. Nonparaneoplastic (n = 22) and paraneoplastic cases (n = 14) were compared. Results: Women accounted for 21 patients (58%). Median age at symptom onset was 67 years (range 18–87 years). We estimated the incidence for Olmsted County was 1.5 per million person-years. Symptom onset was subacute in all. Chorea was focal (20 patients) or generalized (16 patients). Although chorea predominated, other neurologic disorders frequently coexisted (29 patients); abnormal eye movements were uncommon (4 patients). No patient had NMDA receptor antibody or any immunoglobulin (Ig)G yielding a detectable immunofluorescence binding pattern restricted to basal ganglia. Two had synaptic IgG antibodies novel to the context of chorea (GAD65, 1; CASPR2, 1). In the paraneoplastic group, 14 patients had evidence of cancer. Of 13 with a histopathologically confirmed neoplasm, small-cell carcinoma and adenocarcinoma were most common; 6 patients had a cancer-predictive paraneoplastic autoantibody, with CRMP-5–IgG and ANNA-1 being most common. In the idiopathic group, 19 of the 22 patients had a coexisting autoimmune disorder (most frequently systemic lupus erythematosus and antiphospholipid syndrome); autoantibodies were detected in 21 patients, most frequently lupus and phospholipid specificities (19 patients). The paraneoplastic group was older (p = 0.001), more frequently male (p = 0.006), had more frequent weight loss (p = 0.02), and frequently had peripheral neuropathy (p = 0.008). Conclusions: Autoimmune chorea is a rare disorder with rapid onset. Male sex, older age, severe chorea, coexisting peripheral neuropathy, and weight loss increase the likelihood of cancer.
O'Toole, Orna; Lennon, Vanda A.; Ahlskog, J. Eric; Matsumoto, Joseph Y.; Pittock, Sean J.; Bower, James; Fealey, Robert; Lachance, Daniel H.
OBJECTIVE: To evaluate the association between mood and anxiety disorders in Hashimoto disease and Euthyroid Goitre in a case control study. METHODS: Cases included 19 subjects with Hashimoto disease in euthyroid phase, 19 subjects with euthyroid goitre, 2 control groups each of 76 subjects matched (4\\/1) according to age and sex drawn from the data base of a community based
Mauro Carta; Maria Hardoy; Bernardo Carpiniello; Andrea Murru; Anna Marci; Fiora Carbone; Luca Deiana; Mariangela Cadeddu; Stefano Mariotti
Autoimmune hypophysitis (AH) - often referred to as lymphocytic hypophysitis - is a rare disease that affects the pituitary gland and causes inflammation. The disease enlarges the pituitary gland and the clinical presentations are lack of pituitary function and headaches. AH is mostly seen in women 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 immunosuppressive treatment or surgery. PMID:20412729
Krarup, Therese; Hagen, Claus
Recently, several novel, potentially lethal, and treatment-responsive syndromes that affect hippocampal and cortical function have been shown to be associated with auto-antibodies against synaptic antigens, notably glutamate or GABA-B receptors. Patients with these auto-antibodies, sometimes associated with teratomas and other neoplasms, present with psychiatric symptoms, seizures, memory deficits, and decreased level of consciousness. These symptoms often improve dramatically after immunotherapy or tumor resection. Here we discuss studies of the cellular and synaptic effects of these antibodies in hippocampal neurons in vitro and preliminary work in rodent models. Our work suggests that patient antibodies lead to rapid and reversible removal of neurotransmitter receptors from synaptic sites, leading to changes in synaptic and circuit function that in turn are likely to lead to behavioral deficits. We also discuss several of the many questions raised by these and related disorders. Determining the mechanisms underlying these novel anti-neurotransmitter receptor encephalopathies will provide insights into the cellular and synaptic bases of the memory and cognitive deficits that are hallmarks of these disorders, and potentially suggest avenues for therapeutic intervention.
Moscato, Emilia H.; Jain, Ankit; Peng, Xiaoyu; Hughes, Ethan G.; Dalmau, Josep; Balice-Gordon, Rita 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. PMID:22938935
Ponto, Katharina A; Kahaly, George J
Innate immune sensors of foreign nucleic acids are essential for antiviral immunity, but these same sensors can cause autoimmune disease through inappropriate detection of self nucleic acids. The sources of the endogenous RNA and DNA that trigger autoreactive responses include chromatin and ribonucleoproteins that are the targets of autoantibodies in numerous autoimmune diseases, including systemic lupus erythematosus (SLE). In this review, I discuss recent data implicating endogenous retroelements – viruses that make up a substantial fraction of our genomes – as an important source of endogenous nucleic acids that can cause autoimmune disease. Understanding this potentially pathologic role for retroelements and the precise mechanisms by which their genomes are sensed and metabolized has important implications for the diagnosis and treatment of numerous autoimmune disorders.
Stetson, Daniel B.
Autoimmune diseases present with varied and broad-ranging cutaneous manifestations. Connective tissue disorders have a plethora of skin manifestations such as rheumatoid nodules in rheumatoid arthritis, psoriatic plaques in psoriatic arthritis, acne and pustulosis in SAPHO syndrome, livedo reticularis and ulceration in antiphospholipid antibody syndrome and xerosis in Sjögren syndrome. Cutaneous manifestations of autoimmune vasculitides such as polyarteritis nodosa, Kawasaki disease,
Shadi Rashtak; Mark R. Pittelkow
The causes of encephalitis are numerous, and extensive investigations for infectious agents and other etiologies are often negative. The discovery that many of these encephalitis are immune mediated has changed the approach to the diagnosis and treatment of these disorders. Moreover, the broad spectrum of symptoms including, psychosis, catatonia, alterations of behavior and memory, seizures, abnormal movements, and autonomic dysregulation usually requires a multidisciplinary treatment approach. This review focuses in several forms of encephalitis that occur in children, and for which an autoimmune etiology has been demonstrated (eg, anti-N-methyl-D-aspartate receptor encephalitis) or is strongly suspected (eg, Rasmussen encephalitis, limbic encephalitis, opsoclonus-myoclonus). The authors also review several disorders that may be immune mediated, such as the rapid onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) syndrome and some encephalopathies with fever and status epilepticus. Recognition of novel immune-mediated encephalitis is important because some of these disorders are highly responsive to immunotherapy.
Armangue, Thais; Petit-Pedrol, Mar; Dalmau, Josep
The causes of encephalitis are numerous, and extensive investigations for infectious agents and other etiologies are often negative. The discovery that many of these encephalitis are immune mediated has changed the approach to the diagnosis and treatment of these disorders. Moreover, the broad spectrum of symptoms including, psychosis, catatonia, alterations of behavior and memory, seizures, abnormal movements, and autonomic dysregulation usually requires a multidisciplinary treatment approach. This review focuses in several forms of encephalitis that occur in children, and for which an autoimmune etiology has been demonstrated (eg, anti-N-methyl-d-aspartate receptor encephalitis) or is strongly suspected (eg, Rasmussen encephalitis, limbic encephalitis, opsoclonus-myoclonus). The authors also review several disorders that may be immune mediated, such as the rapid onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) syndrome and some encephalopathies with fever and status epilepticus. Recognition of novel immune-mediated encephalitis is important because some of these disorders are highly responsive to immunotherapy. PMID:22935553
Armangue, Thaís; Petit-Pedrol, Mar; Dalmau, Josep
Gangliosides are sialic acid-containing glycolipids which are formed by a hydrophobic portion, the ceramide, and a hydrophilic part, i.e. the oligosaccharide chain. First described in neural tissue, several studies have shown that gangliosides are almost ubiquitous molecules expressed in all vertebrate tissues. Within cells, gangliosides are usually associated with plasma membranes, where they can act as receptors for a variety of molecules and have been shown to take part in cell-to-cell interaction and in signal transduction. In addition, gangliosides are expressed in cytosol membranes like those of secretory granules of some endocrine cells (adrenal medulla, pancreatic islets). As far as the role of gangliosides in diseases is concerned, there are some cases in which an aberrant ganglioside expression plays a crucial role in the disease pathogenetic process. These diseases include two major forms of ganglioside storage, namely GM2-gangliosidosis (Tay-Sachs and its beta-hexosaminidase deficiency) and GM1-gangliosidosis (beta-galactosidase deficiency), where the most prominent pathological characteristic is the lysosomal ganglioside accumulation in neurons. Other inflammatory or degenerative diseases both within and outside the nervous system have been shown to be associated with an altered pattern of ganglioside expression in the target organ. Since monoclonal antibodies have been discovered and used in immunology, a large variety of ganglioside antigens has been described both as blood group antigens and as tumour-related antigens. Several studies have also indicated that gangliosides can act not only as antigens, but also as autoantigens. As a matter of fact, auto-antibodies to gangliosides, detected by immunostaining methods performed directly on TLC plates or by ELISA, have been described in several autoimmune disorders such as Guillain-Barré syndrome, multiple sclerosis, lupus erythematosus, Hashimoto's thyroiditis and, last but not least, insulin-dependent (type 1) diabetes mellitus. This last disease is caused by the autoimmune destruction of insulin-producing pancreatic islet cells in genetically predisposed individuals. Autoantibodies and T lymphocytes directed towards multiple islet autoantigens have been detected in the circulation, well before the clinical onset of the disease, in a prodromal phase during which pancreatic islet beta-cells are presumably destroyed. Among the target autoantigens, some are of protein nature but others are acidic glycolipids such as sulphatides158 and the gangliosides GT3, GD3 and especially GM2-1. This last component is specifically expressed in pancreatic islets and has been shown to represent a target of IgG autoantibodies highly associated with diabetes development in first-degree relatives of type 1 diabetic individuals. In addition, the GM2-1 ganglioside appears to be one of the antigens recognized by cytoplasmic ICA, a heterogeneous group of antibodies which specifically react with islets on pancreatic frozen sections. In conclusion, studies performed in the last decade have clearly indicated that gangliosides represent a heterogeneous class of molecules that are involved in several cellular processes that are of crucial importance in physiological as well as in pathological conditions. Interestingly, these molecules, despite their small size, have been shown to represent not only important antigens in tumour immunology but are also able to elicit a specific autoimmune response, thus representing important autoantigens in some autoimmune disorders. It is of interest that, in addition to neurological autoimmune disorders where autoimmunity to gangliosides is frequent and usually of considerable magnitude, an autoimmune response to this class of molecules has been observed in autoimmune diabetes. (ABSTRACT TRUNCATED) PMID:9307889
Misasi, R; Dionisi, S; Farilla, L; Carabba, B; Lenti, L; Di Mario, U; Dotta, F
Background There is increasing evidence of the importance of copy number variants (CNV) in genetic diversity among individuals and populations, as well as in some common genetic diseases. We previously characterized a common 32-kb insertion/deletion variant of the PSORS4 locus at chromosome 1q21 that harbours the LCE3C and LCE3B genes. This variant allele (LCE3C_LCE3B-del) is common in patients with psoriasis and other autoimmune disorders from certain ethnic groups. Results Using array-CGH (Agilent 244 K) in samples from the HapMap and Human Genome Diversity Panel (HGDP) collections, we identified 54 regions showing population differences in comparison to Africans. We provided here a comprehensive population-genetic analysis of one of these regions, which involves the 32-kb deletion of the PSORS4 locus. By a PCR-based genotyping assay we characterised the profiles of the LCE3C_LCE3B-del and the linkage disequilibrium (LD) pattern between the variant allele and the tag SNP rs4112788. Our results show that most populations tend to have a higher frequency of the deleted allele than Sub-Saharan Africans. Furthermore, we found strong LD between rs4112788G and LCE3C_LCE3B-del in most non-African populations (r2 >0.8), in contrast to the low concordance between loci (r2 <0.3) in the African populations. Conclusions These results are another example of population variability in terms of biomedical interesting CNV. The frequency distribution of the LCE3C_LCE3B-del allele and the LD pattern across populations suggest that the differences between ethnic groups might not be due to natural selection, but the consequence of genetic drift caused by the strong bottleneck that occurred during “out of Africa” expansion.
Context: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are thyroid autoimmune disorders driven by Th1 and Th2 immune responses, respectively. Caveolin-1 (Cav-1), thyroid peroxidase (TPO), and dual oxidase (DUOX) are thought to be part of the thyroxisome, which is essential to maintain thyroid hormone synthesis, at the apical membrane. Objectives: To analyze the thyroxisome in HT and GD thyroids, we investigated Cav-1, DUOX, and TPO expression as well as markers of oxidative stress (OS), cell proliferation, apoptosis, and antioxidant defenses. The effects of cytokines on Cav-1 expression were analyzed in vitro. Results: In HT, the decrease in Cav-1, DUOX, and TPO expression was marked in follicles having the morphological aspect of active follicles in normal glands and thus called active-like follicles. T4 was not detected in the colloid but in the cytoplasm as well as DUOX and TPO. These abnormalities were associated with increased OS and cell damage. In the hypofunctioning follicles of HT and normal thyroids, Cav-1, DUOX, and TPO were not expressed. In GD, they were expressed at the apical pole of thyrocytes, and T4 accumulated in the colloid of all follicles. Th1 cytokines IL-1?/interferon? decreased Cav-1 expression in vitro, whereas the Th2 cytokine IL-4 had no effect. Conclusion: Th1 cytokine-induced down-regulation of Cav-1 could be responsible for intracytoplasmic T4 synthesis and mislocalization of DUOX and TPO, suggesting an important role for Cav-1 in the preservation of thyroxisome integrity. The thyroxisome's disruption, leading to uncontrolled OS and cell apoptosis, is a key, event in HT pathogenesis. PMID:24476075
Marique, Lancelot; Van Regemorter, Victoria; Gérard, Anne-Catherine; Craps, Julie; Senou, Maximin; Marbaix, Etienne; Rahier, Jacques; Daumerie, Chantal; Mourad, Michel; Lengelé, Benoît; Colin, Ides M; Many, Marie-Christine
Visceral leishmaniasis (VL) is a vector-borne protozoal infection caused by replication of Leishmania species in macrophages. VL is characterized by fever, hepatosplenomegaly and cytopenia. Apart from those classic clinical characteristics, VL has been associated with autoimmune clinical and laboratory features. Reported herein are 16 consecutive patients with VL who were checked for laboratory autoimmune manifestations. A variety of autoimmune antibodies including elevated titers of antinuclear antibodies and rheumatoid factor were detected in all patients. Of note, no laboratory autoimmune manifestations were detected in the seven patients who were re-evaluated 3 months after therapy. It is concluded that autoimmune laboratory manifestations during VL infection are common. These may mistakenly lead to diagnosis of an autoimmune disorder. PMID:22516744
Liberopoulos, Evangelos; Kei, Anastazia; Apostolou, Fotini; Elisaf, Moses
Hemophagocytic syndrome (HPS) is a clinicopathological condition characterized by the activation of histiocytes with prominent hemophagocytosis in bone marrow and other reticuloendothelial systems. The occurrence of HPS is usually associated with underlying disorders such as infection and lymphoma. Recently, we described patients with autoimmune disease who developed HPS. In these cases there was no evidence of underlying infection and malignancy,
Shunichi Kumakura; Hiroto Ishikura; Masahiro Kondo; Yohko Murakawa; Junichi Masuda; Shotai Kobayashi
Autoimmune (lymphocytic) hypophysitis is a rare disease that should be considered in the differential diagnosis of any nonsecreting pituitary mass, especially when occurring during pregnancy or postpartum. We have analyzed 370 articles published from January 1962 to October 2004 and identified a total of 379 patients with primary lymphocytic hypophysitis. The present review synthesizes the clinical and research data reported in this body of scientific literature. PMID:15634713
Caturegli, Patrizio; Newschaffer, Craig; Olivi, Alessandro; Pomper, Martin G; Burger, Peter C; Rose, Noel R
This overview of the thyroid autoimmunity in human presents the various facets of a very common pathology. Focus is rather on fundamental than clinical aspects, although some specific clinical situations are discussed. Epidemiology, pathophysiology and pathology of AITD are detailed. One of the peculiarities of AITD is that they express two opposed phenotypes, hypothyroid thyroiditis and hyperthyroid Graves' disease. The latter is characterised by the presence of a unique type of autoantibodies, the anti-TSH receptor antibodies. Those are capable to activate the TSH receptor leading to the gland hypertrophy and hyperfunction. On the contrary, the autoimmune thyroiditis processus progressively and slowly tends to the necrosis/apoptosis of thyroid cells and their functional impairment. Other forms of autoimmune thyroiditis, postpartum thyroiditis and silent thyroiditis are also described. This review, which is not exhaustive, aims at providing a wide scope on the AITD, a basis from which the interested reader or the specialist will be able to find routes towards deeper knowledge. PMID:23164679
A new symptom-complex is described characterized by manifestations of autoimmune disease, infectious lymphadenopathy, double negative T cells, and impaired activation-induced cell death that developed in late adolescence. Similarities, but also significant differences, to autoimmune lymphoproliferative syndromes (ALPS, Canale-Smith syndrome) and autoimmune lymphoproliferative disease (ALD, Dianzani syndrome), were observed. The main clinical features were recurrent bacterial infections with subsequent lymphadenopathy due to autoimmune neutropenia. Laboratory results revealed a large proportion of alphabetaTCR positive, CD4 negative, CD8 negative, peripheral T cells, and a decreased apoptosis upon activation with phytohemagglutinin and interleukin 2, but normal Fas-mediated apoptosis. Genetic investigations excluded mutations in Fas gene death domain and in the 4 exons of Fas ligand gene. Despite unknown pathogenesis, this new syndrome might belong to the growing group of diseases with defects in apoptosis. PMID:12607726
Hundt, Matthias; Posovszky, Carsten; Schmidt, Reinhold E
Hepatitis C virus (HCV) infection is associated with a number of extrahepatic disorders. The most studied conditions associated with HCV are type II mixed cryoglobulinemia and B cell lymphoma. However, many reports suggest that HCV might also be associated with a number of autoimmune disorders, both organ-specific and not organ-specific. Although concomitant treatment of HCV infection is a confounding factor when ascertaining the actual role of HCV in inducing autoimmune disease, a considerable amount of experimental data indicates that HCV is able to subvert the immune system and consequently induce autoimmunity. In the present review, we report a series of observations which associate chronic HCV infection with the onset of autoimmune disorders.
Paroli, Marino; Iannucci, Gino; Accapezzato, Daniele
Autoimmune neutropenia denotes that the number of circulating polymorphonuclear neutrophils is below 1.5×10(9)/L. This encompasses a wide range of disorders from primary conditions to complications of systemic autoimmune diseases or hematological neoplasms. Antineutrophil autoantibodies are particularly difficult to detect, and their amount does not correlate with the degree of neutropenia. Granulocyte colony-stimulating factor is the first-line therapy, but should be restricted to patients with total absence of neutrophils and/or severe infections. PMID:24418296
Youinou, Pierre; Jamin, Christophe; Le Pottier, Laëtitia; Renaudineau, Yves; Hillion, Sophie; Pers, Jacques-Olivier
Objective To describe clinical characteristics and immunotherapy responses in patients with autoimmune epilepsy. Design Observational, retrospective case series. Setting Mayo Clinic Health System. Patients Thirty-two patients with an exclusive (n=11) or predominant (n = 21) seizure presentation in whom an autoimmune etiology was suspected (on the basis of neural autoantibody [91%], inflammatory cerebrospinal fluid [31%], or magnetic resonance imaging suggesting inflammation [63%]) were studied. All had partial seizures: 81% had failed treatment with 2 or more anti-epileptic drugs and had daily seizures and 38% had seizure semiologies that were multifocal or changed with time. Head magnetic resonance imaging was normal in 15 (47%) at onset. Electroencephalogram abnormalities included interictal epileptiform discharges in 20; electrographic seizures in 15; and focal slowing in 13. Neural autoantibodies included voltage-gated potassium channel complex in 56% (leucine-rich, glioma-inactivated 1 specific, 14; contactin-associated proteinlike 2 specific, 1); glutamic acid decarboxylase 65 in 22%; collapsin response-mediator protein 5 in 6%; and Ma2, N-methyl-D-aspartate receptor, and ganglionic acetylcholine receptor in 1 patient each. Intervention Immunotherapy with intravenous methylprednisolone; intravenous immune globulin; and combinations of intravenous methylprednisolone, intravenous immune globulin, plasmapheresis, or cyclo-phosphamide. Main Outcome Measure Seizure frequency. Results After a median interval of 17 months (range, 3–72 months), 22 of 27 (81%) reported improvement postimmunotherapy; 18 were seizure free. The median time from seizure onset to initiating immunotherapy was 4 months for responders and 22 months for nonresponders (P<.05). All voltage-gated potassium channel complex antibody–positive patients reported initial or lasting benefit (P<.05). One voltage-gated potassium channel complex antibody–positive patient was seizure free after thyroid cancer resection; another responded to antiepileptic drug change alone. Conclusion When clinical and serological clues suggest an autoimmune basis for medically intractable epilepsy, early-initiated immunotherapy may improve seizure outcome.
Quek, Amy M. L.; Britton, Jeffrey W.; McKeon, Andrew; So, Elson; Lennon, Vanda A.; Shin, Cheolsu; Klein, Christopher J.; Watson, Robert E.; Kotsenas, Amy L.; Lagerlund, Terrence D.; Cascino, Gregory D.; Worrell, Gregory A.; Wirrell, Elaine C.; Nickels, Katherine C.; Aksamit, Allen J.; Noe, Katherine H.; Pittock, Sean J.
Background Autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated form of diffuse autonomic failure. Many patients have serum antibodies that bind to the ganglionic acetylcholine receptors (AChRs) that mediate fast synaptic transmission in autonomic ganglia. Previous clinical studies and observations in animal models suggest that AAG is an antibody-mediated neurologic disorder. Methods Using whole-cell patch clamp techniques, we recorded ganglionic AChR currents in cultured human IMR-32 cells and examined the effects of bath application of IgG derived from patients with AAG. Results IgG from seven patients with AAG all produced a progressive decline in whole-cell ganglionic AChR current, whereas IgG from control subjects had no effect. The effect was abolished at low temperature. Fab antibody fragments had no effect unless a secondary antibody was added concurrently. IgG from one patient also produced a more immediate reduction of ganglionic AChR current. Conclusions The characteristics of antibody-mediated inhibition of ganglionic acetylcholine receptor (AChR) current are consistent with modulation and blocking of the membrane AChR, analogous to the effects of muscle AChR antibodies in myasthenia gravis. Our observations demonstrate that antibodies in patients with autoimmune autonomic ganglionopathy (AAG) cause physiologic changes in ganglionic AChR function and confirm that AAG is an antibody-mediated disorder.
Wang, Z.; Low, P.A.; Jordan, J.; Freeman, R.; Gibbons, C.H.; Schroeder, C.; Sandroni, P.; Vernino, S.
Autoimmune thyroid diseases (Hashimoto thyroiditis, Graves' disease, postpartum thyroiditis, atrophic thyroiditis and drug induced thyroiditis) are prevalent disorders worldwide, especially in women (related to the millieu of sex steroids and X chromosome effects on the thyroid and the immune system). Disruption of thyroid self tolerance, usually induced by an infection, generates abnormal thyroid--immune interactions, implicating an array of cytokines and their receptors. Thyrocytes achieve antigen presenting cell properties which stimulate effector immune cells (Th1, Th2, Th17), in the context of defective immunomodulatory T regulatory cells, resulting in thyroid lymphocytic infiltration and activation of B cells, with production of antibodies against thyroid antigens, thyroid destruction or stimulation, depending on the Th1-Th2 balance. During pregnancy there is a Th2 predominance sustained by the increased glucocorticoid, estrogen and progesteron levels, which allows tolerance versus the histoincompatible fetoplacental unit. In the postpartum period, the return shift Th2 to Th1 favors the occurrence of postpartum thyroiditis. Altered thyroid hormone levels can influence the immune system, and, on the other side, some immune cells secrete TSH, which exerts endocrine and paracrine, cytokine-like effects. Understanding the complex pathogenesis of autoimmune thyroid disorders is crucial for prevention and management. PMID:20446435
Lichiardopol, Corina; Mo?a, Maria
Autoimmune pancreatitis is a relatively rare form of chronic pancreatitis which is characterized by a lymphoplasmatic infiltrate with a storiform fibrosis and often goes along with painless jaundice and discrete discomfort of the upper abdomen. Clinically we distinguish between two subtypes, which differ in terms of their histology, clinical picture and prognosis. Type 1 autoimmune pancreatitis is the pancreatic manifestation of the IgG4-associated syndrome which also involves other organs. About one third of the patients can only be diagnosed after either histological prove or a successful steroid trail. Type 2 is IgG4-negative with the histological picture of an idiopathic duct centric pancreatitis and is to higher degree associated with inflammatory bowel disease. A definitive diagnosis can only be made using biopsy. Usually both forms show response to steroid treatment, but in type 1 up to 50?% of the patients might develop a relapse. The biggest challenge and most important differential diagnosis remains the discrimination of AIP from pancreatic cancer, because also AIP can cause mass of the pancreatic head, lymphadenopathy and ductal obstruction. This article summarizes recent advances on epidemiology, clinical presentation, diagnostic strategy, therapy and differential diagnosis in this relatively unknown disease. PMID:24193862
Beyer, G; Menzel, J; Krüger, P-C; Ribback, S; Lerch, M M; Mayerle, J
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.
Genes and mechanisms involved in common complex diseases, such as the autoimmune disorders that affect approximately 5% of the population, remain obscure. Here we identify polymorphisms of the cytotoxic T lymphocyte antigen 4 gene (CTLA4)-which encodes a vital negative regulatory molecule of the immune system-as candidates for primary determinants of risk of the common autoimmune disorders Graves' disease, autoimmune hypothyroidism
Hironori Ueda; Joanna M. M. Howson; Laura Esposito; Joanne Heward; Hywel Snook; Giselle Chamberlain; Daniel B. Rainbow; Kara M. D. Hunter; Annabel N. Smith; Gianfranco Di Genova; Mathias H. Herr; Ingrid Dahlman; Felicity Payne; Deborah Smyth; Christopher Lowe; Rebecca C. J. Twells; Sarah Howlett; Barry Healy; Sarah Nutland; Helen E. Rance; Vin Everett; Luc J. Smink; Alex C. Lam; Heather J. Cordell; Neil M. Walker; Cristina Bordin; John Hulme; Costantino Motzo; Francesco Cucca; J. Fred Hess; Michael L. Metzker; Jane Rogers; Simon Gregory; Amit Allahabadia; Ratnasingam Nithiyananthan; Eva Tuomilehto-Wolf; Jaakko Tuomilehto; Polly Bingley; Kathleen M. Gillespie; Dag E. Undlien; Kjersti S. Rřnningen; Cristian Guja; Constantin Ionescu-Tîrgoviste; David A. Savage; A. Peter Maxwell; Dennis J. Carson; Chris C. Patterson; Jayne A. Franklyn; David G. Clayton; Laurence B. Peterson; Linda S. Wicker; John A. Todd; Stephen C. L. Gough
ABSTRACT In an autoimmune disease, the immune system attacks and harms the body's own tissues. The systemic autoimmune diseases include collagen vascular diseases, the systemic vasculitides, Wegener granulomatosis, and Churg-Strauss syndrome. These disorders can involve any part of the gastrointestinal tract, hepatobiliary system and pancreas. They can cause a variety of gastrointestinal manifestations that are influenced by the pathophysiologic characteristics of the underlying disease process. There is a wide variation of gastrointestinal manifestations from these autoimmune disorders including, but not limited to: oral ulcers, dysphagia, gastroesophageal reflux disease, abdominal pain, constipation, diarrhea, fecal incontinence, pseudo-obstruction, perforation and gastrointestinal bleeding. Clinical workup should be initiated by the patient's subjective complaints. In this review, we analyze the effects of autoimmune diseases on the gastrointestinal tract.
COJOCARU, M.; COJOCARU, Inimioara Mihaela; SILOSI, Isabela; VRABIE, Camelia Doina
Common variable immunodeficiency (CVID) is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20–50%; Chapel et al., 2008; Cunningham-Rundles, 2008), autoimmune cytopenias are by far the most common occurring variably in 4–20% (Michel et al., 2004; Chapel et al., 2008) of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia, and neutropenia. While it may seem paradoxical “prima facie” that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21 low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID.
Podjasek, Jenna C.; Abraham, Roshini S.
The systemic autoimmune diseases are a complex group of disorders characterized by elaboration of high titer autoantibodies and immune-mediated damage of tissues. Two striking features of autoimmune rheumatic diseases are their self-sustaining nature and capacity for autoamplification, exemplified by disease flares. These features suggest the presence of a feed-forward cycle in disease propagation, in which immune effector pathways drive the
E Darrah; A Rosen
The term autoimmune liver diseases in its common use comprises three types of disorders, namely, autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC),\\u000a and primary sclerosing cholangitis (PSC), as well as their overlap syndromes. Previous reports (1,2) indicated an incidence (identified patients) of 1 to 2:10.000 for AIH, 1:10.000 for PBC, and 0.5:10.000 for PSC. However,\\u000a there is a pronounced probability
Markus Biburger; Gisa Tiegs
\\u000a Autoimmune diseases, which comprise over 80 clinically distinct conditions, are characterized by the presence of autoantibodies\\u000a or autoreactive T cells directed against self structures (autoantigens). While these often incurable disorders appear to be\\u000a rapidly increasing in recognition throughout the world, their rarity, heterogeneity and complex etiologies have limited our\\u000a understanding of their pathogeneses. The precise mechanisms for the development of
Frederick W. Miller
Autoimmune uveitis is a complex group of sight-threatening diseases that arise without a known infectious trigger. The disorder is often associated with immunological responses to retinal proteins. Experimental models of autoimmune uveitis targeting retinal proteins have led to a better understanding of the basic immunological mechanisms involved in the pathogenesis of uveitis and have provided a template for the development of novel therapies. The disease in humans is believed to be T cell-dependent, as clinical uveitis is ameliorated by T cell-targeting therapies. The roles of T helper 1 (Th1) and Th17 cells have been major topics of interest in the past decade. Studies in uveitis patients and experiments in animal models have revealed that Th1 and Th17 cells can both be pathogenic effectors, although, paradoxically, some cytokines produced by these subsets can also be protective, depending on when and where they are produced. The major proinflammatory as well as regulatory cytokines in uveitis, the therapeutic approaches, and benefits of targeting these cytokines will be discussed in this review.
Autoimmune uveitis is a complex group of sight-threatening diseases that arise without a known infectious trigger. The disorder is often associated with immunological responses to retinal proteins. Experimental models of autoimmune uveitis targeting retinal proteins have led to a better understanding of the basic immunological mechanisms involved in the pathogenesis of uveitis and have provided a template for the development of novel therapies. The disease in humans is believed to be T cell-dependent, as clinical uveitis is ameliorated by T cell-targeting therapies. The roles of T helper 1 (Th1) and Th17 cells have been major topics of interest in the past decade. Studies in uveitis patients and experiments in animal models have revealed that Th1 and Th17 cells can both be pathogenic effectors, although, paradoxically, some cytokines produced by these subsets can also be protective, depending on when and where they are produced. The major proinflammatory as well as regulatory cytokines in uveitis, the therapeutic approaches, and benefits of targeting these cytokines will be discussed in this review. PMID:21787221
Horai, Reiko; Caspi, Rachel R
Are Dysregulated Inflammatory Responses to Commensal Bacteria Involved in the Pathogenesis of Hepatobiliary-Pancreatic Autoimmune Disease? An Analysis Using Mice Models of Primary Biliary Cirrhosis and Autoimmune Pancreatitis
The etiopathogenesis of many autoimmune disorders has not been identified. The aim of this paper is to focus on the involvement of bacterial exposure in the pathogenesis of primary biliary cirrhosis (PBC) and autoimmune pancreatitis (AIP), both of which are broadly categorized as autoimmune disorders involving hepatobiliary-pancreatic lesions. Avirulent and/or commensal bacteria, which may have important role(s) as initiating factors in the pathogenesis of autoimmune disorders such as PBC and AIP, will be emphasized.
Yanagisawa, Naoko; Haruta, Ikuko; Kikuchi, Ken; Shibata, Noriyuki; Yagi, Junji
Therapy for autoimmune demyelinating disorders has evolved rapidly over the past 10 years to include traditional immunosuppressants as well as novel biologicals. Antibody-mediated neuromuscular disorders are treated with therapies that acutely modulate pathogenic antibodies or chronically inhibit the humoral immune response. In other inflammatory autoimmune disorders of the peripheral and central nervous system, corticosteroids, often combined with conventional immunosuppression, and immunomodulatory treatments are used. Because autoimmune neurologic disorders are so diverse, evidence from randomized controlled trials is limited for most of the immunotherapies used in neurology. This review provides an overview of the immunotherapies currently used for neurologic disorders. PMID:22703853
Graves, Donna; Vernino, Steven
Autoimmune disorders afflicting the liver comprise the bona fide autoimmune diseases, primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis as well as drug-induced autoimmune-like diseases, such as halothane hepatitis. Whereas drug-induced forms of acute or chronic hepatitis often have a clear triggering factor, the etiology of classical autoimmune liver diseases is only poorly understood. Besides a genetic component present in disease susceptible individuals, environmental triggering factors are likely to play a role in the initiation and/or propagation of the disease. In this article, we will review on current evidence obtained from epidemiological associations, case studies, and findings in animal models for pathogens, to be involved in the etiology of autoimmune liver disease with a special focus on autoimmune hepatitis. PMID:24911790
Christen, Urs; Hintermann, Edith
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disease caused by mutations of the AutoImmune REgulator gene. The clinical spectrum of the disease encompasses several autoimmune endocrine and non-endocrine manifestations, which may lead to acute metabolic alterations and eventually life-threatening events. The clinical diagnosis is defined by the presence of at least two components of the classic triad including chronic mucocoutaneous candidiasis (CMC), chronic hypoparathyroidism (CH), Addison's disease (AD). Other common features of the disease are hypergonadotropic hypogonadism, alopecia, vitiligo, autoimmune hepatitis, Type 1 diabetes, gastrointestinal dysfunction. APECED usually begins in childhood. CMC is the first manifestation to appear, usually before the age of 5 yr, followed by CH and then by AD. The clinical phenotype may evolve over several years and many components of the disease may not appear until the 4th or 5th decade of life. The phenotypical expression of the syndrome shows a wide variability even between siblings with the same genotype. In view of this heterogeneity, an early diagnosis of APECED can be very challenging often leading to a considerable diagnostic delay. Therefore, clinicians should be aware that the presence of even a minor component of APECED in children should prompt a careful investigation for other signs and symptoms of the disease, thus allowing an early diagnosis and prevention of severe and life-threatening events. Aim of this review is to focus on clinical presentation, diagnosis and management of the major components of APECED in children particularly focusing on endocrine features of the disease. PMID:23723078
Capalbo, D; Improda, N; Esposito, A; De Martino, L; Barbieri, F; Betterle, C; Pignata, C; Salerno, M
Systemic autoimmune diseases that are resistant to conventional treatment cause considerable morbidity and mortality. Although\\u000a aggressive new approaches to treating autoimmune diseases have been developed over the past decade, there are still patients\\u000a with a severe, progressive, and life-threatening course. Based on animal studies and experience in the treatment of hematological\\u000a disorders with preexisting autoimmune disease, hematopoietic stem cell transplantation
Alopecia areata (AA) frequently occur in association with other autoimmune diseases such as thyroid disorders, anemias and other skin disorders with autoimmune etiology. Despite numerous studies related to individual disease associations in alopecia areata, there is paucity of literature regarding comprehensive studies on concomitant cutaneous and systemic diseases. The present study has been designed to determine if there is a significant association between alopecia areata and other autoimmune diseases. This study covers 71 patients with the diagnosis of alopecia areata as the case group and 71 patients with no evidence of alopecia areata as the control group. Among the cutaneous diseases associated with AA, atopic dermatitis (AD) showed maximum frequency with an O/E ratio of 2.5, which indicates that it is two to three times more common in patients with alopecia areata. In our study, thyroid disorders showed the highest frequency with on O/E ratio of 3.2 and a P value of 0.01, which is statistically highly significant. Among the thyroid disorders, hypothyroidism was the most frequent association (14.1%) in our study. Since systemic involvement is not infrequent in patients with alopecia areata, it is imperative to screen these patients for associated disorders, particularly atopy, thyroid diseases, anemias and other autoimmune disorders, especially if alopecia areata is chronic, recurrent and extensive.
Thomas, Emy Abi; Kadyan, R S
The contents of this book are: HLA and Autoimmunity; Self-Recognition and Symmetry in the Immune System; Immunology of Insulin Dependent Diabetes Mellitus; Multiple Sclerosis; Autoimmunity and Immune Pathological Aspects of Virus Disease; Analyses of the Idiotypes and Ligand Binding Characteristics of Human Monoclonal Autoantibodies to DNA: Do We Understand Better Systemic Lupus Erythematosus. Autoimmunity and Rheumatic Fever; Autoimmune Arthritis Induced by Immunization to Mycobacterial Antigens; and The Interaction Between Genetic Factors and Micro-Organisms in Ankylosing Spondylitis: Facts and Fiction.
Autoimmune blistering dermatoses are examples of skin-specific autoimmune disorders that can sometimes represent the cutaneous manifestation of a multiorgan disease due to potential common pathogenic mechanisms. As soon as a distinct autoimmune blistering dermatosis is diagnosed, it is imperative to consider its potential systemic involvement, as well as the autoimmune and inflammatory conditions that are frequently associated with it. In paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, the internal organs (particularly the lungs) are affected by the autoimmune injury. Pemphigus erythematosus may manifest with overlapping serologic and immunohistologic features of lupus erythematosus. In patients with bullous pemphigoid, there is a greater prevalence of neurologic disease, possibly caused by cross-reactivity of the autoantibodies with isoforms of bullous pemphigoid antigens expressed in the skin and brain. Anti-laminin 332 pemphigoid shows an increased risk for adenocarcinomas. Patients with anti-p200 pemphigoid often suffer from psoriasis. A rare form of pemphigoid with antibodies against the ?5 chain of type IV collagen is characterized by underlying nephropathia. Particularly interesting is the association of linear IgA disease or epidermolysis bullosa acquisita with inflammatory bowel disease. Dermatitis herpetiformis is currently regarded as the skin manifestation of gluten sensitivity. Bullous systemic lupus erythematosus is part of the clinical spectrum of systemic lupus erythematosus, a prototypic autoimmune disease with multisystem involvement. PMID:24767184
Vassileva, Snejina; Drenovska, Kossara; Manuelyan, Karen
Type 1 diabetic children and adolescents often present with autoimmune thyroid disorders. Two hundred and four diabetic patients, less than 20 years old, were studied in order to diagnose these diseases. The prevalence of thyroid autoimmune disorders was 17.6% and, of those, chronic autoimmune thyroiditis was the most frequent. Microsomal autoantibodies correlated more accurately with the presence of chronic autoimmune thyroiditis than thyroglobulin autoantibodies. The thyroid status of most of the patients with positive markers was euthyroidism (77%), but subclinical hypothyroidism (11%), overt hypothyroidism (3%), subclinical hyperthyroidism (3%) and overt hyperthyroidism (6%) were also present. Autoimmune thyroid disorders were the most prevalent immunological processes affecting diabetic patients. No significant associations of thyroid autoimmunity and other autoimmunological disorders, such as celiac disease or presence of other autoimmune antibodies, were found. PMID:10517303
Roldán, M B; Alonso, M; Barrio, R
The association of immune dysfunction in patients with human immunodeficiency virus (HIV) infection and AIDS and the development of autoimmune diseases is intriguing. Yet, the spectrum of reported autoimmune phenomena in these patients is increasing. An infectious trigger for immune activation is one of the postulated mechanisms and derives from molecular mimicry. During frank loss of immunocompetence, autoimmune diseases that
Gisele Zandman-Goddard; Yehuda Shoenfeld
The autoimmune thyroid diseases, Graves' disease and autoimmune hypothyroidism, represent the two ends of a disease spectrum where an immune response is directed against the thyroid gland. In Graves' disease, antibodies directed against the thyrotropin receptor (TSH-R) lead to the development of glandular overactivity, while in autoimmune hypothyroidism, cell-mediated and humoral thyroid injury leads to destruction of thyroid tissue and
Joanne Collins; Stephen Gough
The clinical course of chronic lymphocytic leukemia (CLL) may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Pure red cell aplasia (PRCA) and autoimmune agranulocytosis (AG) are, indeed, more rarely seen. However, they are probably underestimated due to the possible misleading presence of cytopenias secondary to leukemic bone marrow involvement or to chemotherapy cytotoxicity. The source of autoantibodies is still uncertain, despite the most convincing data are in favor of the involvement of resting normal B-cells. In general, excluding the specific treatment of underlying CLL, the managementof these complications is not different from that of idiopathic autoimmune cytopenias or of those associated to other causes. Among different therapeutic approaches, monoclonal antibody rituximab, given alone or in combination, has shown to be very effective. PMID:23690826
D'Arena, Giovanni; Guariglia, Roberto; La Rocca, Francesco; Trino, Stefania; Condelli, Valentina; De Martino, Laura; De Feo, Vincenzo; Musto, Pellegrino
TNF-? is a crucial cytokine in the establishment and maintenance of inflammation in multiple autoimmune and non-autoimmune disorders. A number of large placebo-controlled trials have shown that infliximab, a chimeric monoclonal antibody against TNF-?, is effective and well-tolerated in patients with Crohn's disease and rheumatoid arthritis (RA) and has become a widely used treatment for these diseases. More recent controlled
Fabiola Atzeni; Piercarlo Sarzi-Puttini; Andrea Doria; Luca Iaccarino; Franco Capsoni
Allergic and autoimmune diseases have been considered to be at the opposite sides of the spectrum of the immune response. Autoimmune diseases, such as multiple sclerosis (MS), rheumatoid arthritis and type 1 insulin-dependent diabetes mellitus, are considered T helper 1 (Th1)-mediated diseases, and allergic disorders, such as asthma, food allergy or rhinitis, are considered to be Th2-mediated. In this Opinion,
Rosetta Pedotti; Jason J. De Voss; Lawrence Steinman; Stephen J. Galli
Pituitary autoimmunity encompasses a spectrum of conditions ranging from histologically proven forms of lymphocytic hypophysitis to the presence of pituitary antibodies in apparently healthy subjects. Hypophysitis is a rare but increasingly recognized disorder that typically presents as a mass in the sella turcica. It mimics clinically and radiologically other non-functioning sellar masses, such as the more common pituitary adenoma. Hypophysitis shows a striking temporal association with pregnancy, and it has been recently described during immunotherapies that block CTLA-4. Several candidate pituitary autoantigens have been described in the last decade, although none has proven useful as a diagnostic tool. This review summarizes the advances made in the field since the publication of the first review on pituitary autoimmunity, and the challenges that await clarification. PMID:18774118
Caturegli, Patrizio; Lupi, Isabella; Landek-Salgado, Melissa; Kimura, Hiroaki; Rose, Noel R
Chronic granulomatous disease (CGD) is characterized by recurrent infections and granuloma formation. In addition, we have observed a number of diverse autoimmune conditions in our CGD population, suggesting that patients with CGD are at an elevated risk for development of autoimmune (AI) disorders. In this report, we describe antiphospholipid syndrome (aPL), recurrent pericardial effusion, juvenile idiopathic arthritis (JIA), IgA nephropathy, cutaneous lupus erythematosus, and autoimmune pulmonary disease in the setting of CGD. The presence and type of autoimmune disease has important treatment implications for patients with CGD.
De Ravin, Suk See; Naumann, Nora; Cowen, Edward W.; Friend, Julia; Hilligoss, Dianne; Marquesen, Martha; Balow, James E.; Barron, Karyl S.; Turner, Maria L.; Gallin, John I.; Malech, Harry L.
Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis
Background Generalized vitiligo is an autoimmune disease of skin pigmentation that is associated with increased prevalence of other autoimmune diseases, particularly autoimmune thyroid disease (AITD; principally Hashimoto's disease and Graves' disease), both in vitiligo patients and their close relatives, suggesting a heritable predisposition involving, in part, shared susceptibility genes. Summary This review summarizes current knowledge of vitiligo epidemiology and genetics, highlighting recent findings from genome-wide approaches to disease gene identification, emphasizing susceptibility loci shared with other autoimmune diseases, particularly AITD, as well as some important differences. Conclusions Inherited susceptibility to generalized vitiligo involves a number of specific genes, many of which are shared with other autoimmune diseases that are epidemiologically associated with vitiligo, including AITD, confirming a longstanding hypothesis about the genetic basis of these disorders. These genes provide potential therapeutic targets for novel approaches to treatment as well as for approaches to presymptomatic diagnosis and disease prevention in individuals with inherited susceptibility to this group of autoimmune diseases.
Systemic autoimmune disorders may affect several organs, including the heart. We analyzed two-dimensional and pulsed Doppler echocardiograms of patients (n = 37) with systemic lupus erythematosus (SLE, n = 24) or rheumatoid arthritis (RA, n = 13) to determine whether atrial ejection force (AEF) could represent a suitable parameter for detecting left ventricular filling abnormalities in SLE and RA. In
Roland Jahns; Johji Naito; Hans-Peter Tony; Gerhard Inselmann
Autoimmune diseases and malignant lymphomas have numerous similarities in their etiology and pathogenesis. Patients with autoimmune\\u000a disorders have increased risk to develop non-Hodgkin's lymphomas, yet little is known about the occurrence of autoimmune features\\u000a within lymphoma patients. Our aim was to examine the prevalence of autoimmune diseases among patients with non-Hodgkin's (NHL)\\u000a and Hodgkin's lymphoma (HL). We reviewed 352 patients'
László Váróczy; Zsuzsanna Kádár; Lajos Gergely; Zsófia Miltényi; Ferenc Magyari; Péter Szodoray; Árpád Illés
The sense of smell is an ancient sensory modality vital for sampling and perceiving the chemical composition of surrounding environments. Olfaction involves a pathway of biochemical and electrophysiological processes, which allows the conversion of molecular information into sensations. Disturbances in the olfactory function have been investigated mainly in neurological/neurodegenerative disorders such as Alzheimer's and Parkinson's diseases; impaired sense of smell has been associated with depressed mood. Only recently, smell capability was tested in other diseases, particularly autoimmune diseases. Shoenfeld and colleagues opened this chapter showing that patients affected with systemic lupus erythematosus (SLE) have disturbances in their olfactory functions and revealed its association with neuropsychiatric manifestations of the disease. This evidence was confirmed in experimental models and replicated in other SLE populations. The connection between autoimmunity and the sense of smell was lately emphasized by studies on patients with Sjögren's syndrome and in patients with other autoimmune/immune-mediated diseases, such as polydermatomyositis, recurrent spontaneous abortion, and hereditary angioedema. Genetic susceptibility and hormonal and environmental factors may play a role in these conditions. Olfactory receptor gene clusters are located in proximity to key locus of susceptibility for autoimmune diseases such as the major histocompatibility complex, suggesting not only a physic linkage, but a functional association. Nonetheless, gender- and hormone-mediated effects are fundamental in the development of autoimmune diseases. The different connections between smell and autoimmunity, genes and hormones may suggest that this is another tessera of a mosaic which is waiting the answer of Oedipus. PMID:23233263
Perricone, Carlo; Shoenfeld, Netta; Agmon-Levin, Nancy; de Carolis, Caterina; Perricone, Roberto; Shoenfeld, Yehuda
The systemic autoimmune diseases are a complex group of disorders characterized by elaboration of high titer autoantibodies and immune-mediated damage of tissues. Two striking features of autoimmune rheumatic diseases are their self-sustaining nature and capacity for autoamplification, exemplified by disease flares. These features suggest the presence of a feed-forward cycle in disease propagation, in which immune effector pathways drive the generation/release of autoantigens, which in turn fuel the immune response. There is a growing awareness that structural modification during cytotoxic granule-induced cell death is a frequent and striking feature of autoantigens, and may be an important principle driving disease. This review focuses on granzyme B (GrB)-mediated cleavage of autoantigens including (i) features of GrB cleavage sites within autoantigens, (ii) co-location of cleavage sites with autoimmune epitopes, and (iii) GrB sensitivity of autoantigens in disease-relevant target tissue. The mechanisms whereby GrB-induced changes in autoantigen structure may contribute to the initiation and propagation of autoimmunity are reviewed and reveal that GrB has the potential to create or destroy autoimmune epitopes. As there remains no direct evidence showing a causal function for GrB cleavage of antigens in the generation of autoimmunity, this review highlights important outstanding questions about the function of GrB in autoantigen selection. PMID:20075942
Darrah, E; Rosen, A
Human cytomegalovirus (HCMV) represents a prototypic pathogenic member of the ?-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE), systemic sclerosis (SSc), diabetes mellitus type 1, and rheumatoid arthritis (RA) is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28? T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention.
Fc receptors are a critical component of the innate immune system responsible for the recognition of cross-linked antibodies and the subsequent clearance of pathogens. However, in autoimmune diseases, these receptors play a role in the deleterious action of self-directed antibodies and as such are candidate targets for treatment. GMA161 is an aglycosyl, humanized version of the murine antibody 3G8 that targets the human low-affinity Fc? receptor III (CD16). As CD16 expression and sequence have high species specificity, preclinical assessments were conducted in mice transgenic for both isoforms of human CD16, CD16A, and CD16B. This transgenic mouse model was useful in transitioning into phase I clinical trials, as it generated positive efficacy data in a relevant disease model and an acceptable single-dose safety profile. However, when GMA161 or its murine parent 3G8 were dosed repeatedly in transgenic mice having both human CD16 isoforms, severe reactions were observed that were not associated with significant cytokine release, nor were they alleviated by antihistamine administration. Prophylactic dosing with an inhibitor of platelet-activating factor (PAF), however, completely eliminated all signs of hypersensitivity. These findings suggest that (1) GMA161 elicits a reaction that is target dependent, (2) immunogenicity and similar adverse reactions were observed with a murine version of the antibody, and (3) the reaction is driven by the atypical hypersensitivity pathway mediated by PAF. PMID:22025730
Flaherty, Meghan M; MacLachlan, Timothy K; Troutt, Misty; Magee, Tomas; Tuaillon, Nadine; Johnson, Syd; Stein, Kathryn E; Bonvini, Ezio; Garman, Richard; Andrews, Laura
Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. PMID:23149338
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
Uncompensated autoantibody-mediated red blood cell (RBC) consumption is the hallmark of autoimmune hemolytic anemia (AIHA). Classification of AIHA is pathophysiologically based and divides AIHA into warm, mixed or cold-reactive subtypes. This thermal-based classification is based on the optimal autoantibody-RBC reactivity temperatures. AIHA is further subcategorized into idiopathic and secondary with the later being associated with a number of underlying infectious, neoplastic and autoimmune disorders. In most cases AIHA is confirmed by a positive direct antiglobulin test (DAT). The standard therapeutic approaches to treatment of AIHA include corticosteroids, splenectomy, immunosuppressive agents and monoclonal antibodies. PMID:24418298
Bass, Garrett F; Tuscano, Emily T; Tuscano, Joseph M
Background Copy number variation (CNV) contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT) method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. Results We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. Conclusions Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion.
Strong direct and indirect evidence supports an autoimmune etiology for alopecia areata. T lymphocytes that have been shown to be oligoclonal and autoreactive are predominantly present in the peribulbar inflammatory infiltrate. Alopecia areata frequently occurs in association with other autoimmune diseases, such as thyroiditis and vitiligo, and autoantibodies to follicular components have been detected. Finally, the use of immune modulating
Maria Hordinsky; Marna Ericson
The high percentage of disease-discordant pairs of monozygotic twins demonstrates the central role of environmental factors in the etiology of autoimmune diseases. Efforts were first focussed on the search for triggering factors. The study of animal models has clearly shown that infections may trigger autoimmune diseases, as in the case of Coxsackie B4 virus in type I diabetes and the
The etiology of autoimmune diseases remains largely unknown. Concordance rates in monozygotic twins are lower than 50% while genome-wide association studies propose numerous significant associations representing only a minority of patients. These lines of evidence strongly support other complementary mechanisms involved in the regulation of genes expression ultimately causing overt autoimmunity. Alterations in the post-translational modification of histones and DNA
Francesca Meda; Marco Folci; Andrea Baccarelli; Carlo Selmi
Résumé Les maladies auto-immunes du foie, en particulier la cirrhose biliaire primitive (CBP) et les hépatites auto-immunes (HAI)\\u000a sont des maladies spécifiques d’organes dont la définition est ŕ la fois clinique, histologique et biologique. La recherche\\u000a des autoanticorps sériques est une étape essentielle ŕ leur diagnostic (1).
C. Johanet; E Ballot
Myeloid derived suppressor cells (MDSC) were first described nearly two decades ago. Until recently, however, descriptions of MDSC populations were found almost exclusively in animal models of cancer or in cancer patients. Over the last few years, an increasing number of reports have been published describing populations of myeloid cells with MDSC-like properties in murine models of autoimmune disease. In contrast to the proposed deleterious role of MDSC in cancer - where these cells likely inhibit tumor immunity - in the context of autoimmunity, MDSC have the potential to suppress the autoimmune response, thereby limiting tissue injury. A logical corollary of this hypothesis is that a failure of endogenous MDSC to appropriately control autoimmune T cell responses in vivo may actually contribute to the pathogenesis of autoimmune disease.
Cripps, James G.; Gorham, James D.
Type 1 diabetes (T1D) results from autoimmune-mediated loss of insulin-producing beta-cells. Recent findings suggest that the events controlling T1D development are not only immunological, but also neuronal in nature. In the non-obese diabetic (NOD) mouse model of T1D, a mutant sensory neuron channel, TRPV1, initiates chronic, progressive beta-cell stress, inducing islet cell inflammation. This novel mechanism of organ-specific damage requires a permissive, autoimmune-prone host, but ascribes tissue specificity to the local secretory dysfunction of sensory afferent neurons. In NOD mice, normalizing this neuronal function by administration of the neurotransmitter substance P clears islet cell inflammation, reduces insulin resistance and restores normoglycemia. Here, we discuss this neuro-immuno-endocrine model, its implications and the involvement of sensory neurons in other autoimmune disorders. These developments might provide novel neuronal-based therapeutic interventions, particularly in diabetes. PMID:17900987
Tsui, Hubert; Razavi, Rozita; Chan, Yin; Yantha, Jason; Dosch, H-Michael
The association of immune dysfunction in patients with human immunodeficiency virus (HIV) infection and AIDS and the development of autoimmune diseases is intriguing. Yet, the spectrum of reported autoimmune phenomena in these patients is increasing. An infectious trigger for immune activation is one of the postulated mechanisms and derives from molecular mimicry. During frank loss of immunocompetence, autoimmune diseases that are predominantly T cell subtype CD8 driven predominate. There is evidence for B cell stimulation and many autoantibodies are reported in HIV patients. We propose a staging of autoimmune manifestations related to HIV/AIDS manifestations and the total CD4 count and viral load that may be beneficial in identifying the type of autoimmune disease and establishing the proper therapy. In stage I there is the acute HIV infection, and the immune system is intact. In this stage, autoimmune diseases may develop. Stage II describes the quiescent period without overt manifestations of AIDS. However, there is a declining CD4 count indicative of some immunosuppression. Autoimmune diseases are not found. During stage III there is immunosuppression with a low CD4 count and the development of AIDS. CD8 T cells predominant and diseases such as psoriasis and diffuse immune lymphocytic syndrome (similar to Sjogren's syndrome) may present or even be the initial manifestation of AIDS. Also during this stage no autoimmune diseases are found. In stage IV there is restoration of immune competence following highly active anti-retroviral therapy (HAART). In this setting, there is a resurgence of autoimmune diseases. The frequency of reported rheumatological syndromes in HIV-infected patients ranges from 1 to 60%. The list of reported autoimmune diseases in HIV/AIDS include systemic lupus erythematosus, anti-phospholipid syndrome, vasculitis, primary biliary cirrhosis, polymyosits, Graves' disease, and idiopathic thrombocytopenic purpura. Also, there is an array of autoantibodies reported in HIV/AIDS patients which include anti-cardiolipin, anti-beta2 GPI, anti-DNA, anti-small nuclear ribonucleoproteins (snRNP), anti-thyroglobulin, anti-thyroid peroxidase, anti-myosin, and anti-erythropoietin antibodies. The association of autoantibodies in HIV-infected patients to clinical autoimmune disease is yet to be established. With the upsurge of HAART, the incidence of autoimmune diseases in HIV-infected patients is increasing. In this review, we describe the various autoimmune diseases that develop in HIV/AIDS patients through possible mechanisms related to immune activation. PMID:12848988
Zandman-Goddard, Gisele; Shoenfeld, Yehuda
Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies.
Michels, Aaron W.; Eisenbarth, George S.
Background: Autoimmune polyglandular syndrome type 1 (APS-1) (OMIM 240300) is a rare autosomal recessive disorder associated with three major manifestations: chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. There are, however, multiple minor components of APS-1 that induce significant phenotype variability. Subsequently, the diagnosis of APS-1 during early stages is often challenging. Aim: We aimed to provide clinical and mutational data
Elizaveta M. Orlova; Anna M. Bukina; Elvira S. Kuznetsova; Maria A. Kareva; Ekaterina U. Zakharova; Valentina A. Peterkova; Ivan I. Dedov
Blister formation in skin and mucous membranes results from a loss of cell-cell or cell-matrix adhesion and is a common outcome of pathological events in a variety of conditions, including autoimmune and genetic diseases, viral and bacterial infections, or injury by physical and chemical factors. Autoantibodies against structural components maintaining cell-cell and cell-matrix adhesion induce tissue damage in autoimmune blistering diseases. Detection of these autoantibodies either tissue-bound or circulating in serum is essential to diagnose the autoimmune nature of disease. Various immunofluorescence methods as well as molecular immunoassays, including enzyme-linked immunosorbent assay and immunoblotting, belong to the modern diagnostic algorithms for these disorders. There is still a considerable need to increase awareness of the rare autoimmune blistering diseases, which often show a severe, chronic-relapsing course, among physicians and the public. This review article describes the immunopathological features of autoimmune bullous diseases and the molecular immunoassays currently available for their diagnosis and monitoring.
Otten, J.V.; Hashimoto, T.; Hertl, M.; Payne, A.S.; Sitaru, C.
Chronic urticaria is common and patients may present with transient eruption of itchy, eruthematous, edematous swellings of the dermis, which lasts more than six weeks. One type of chronic idiopathic urticaria, and part of it, is the chronic autoimmune urticaria. The chronic autoimmune urticaria is caused by high affinity of IgE receptors (anti-FcRI) and less frequently by anti-IgE autoantibodies, also the role of complement activation, that leads to mast and basophil activation. Despite many recent advances in the understanding of chronic autoimmune urticaria, this condition remains a major challenge in the terms of its etiology, investigations, and management. PMID:22745150
Wardhana; Datau, E A
Autoimmune diseases have increased dramatically worldwide since World War II. This is coincidental with the increased production and use of chemicals both in industrial countries and agriculture, as well as the ease of travel from region to region and continent to continent, making the transfer of a pathogen or pathogens from one part of the world to another much easier than ever before. In this review, triggers of autoimmunity are examined, principally environmental. The number of possible environmental triggers is vast and includes chemicals, bacteria, viruses, and molds. Examples of these triggers are given and include the mechanism of action and method by which they bring about autoimmunity. PMID:24900918
Campbell, Andrew W
Autoimmune diseases have increased dramatically worldwide since World War II. This is coincidental with the increased production and use of chemicals both in industrial countries and agriculture, as well as the ease of travel from region to region and continent to continent, making the transfer of a pathogen or pathogens from one part of the world to another much easier than ever before. In this review, triggers of autoimmunity are examined, principally environmental. The number of possible environmental triggers is vast and includes chemicals, bacteria, viruses, and molds. Examples of these triggers are given and include the mechanism of action and method by which they bring about autoimmunity.
Campbell, Andrew W.
Autoimmune pancreatitis (AIP) is a recently discovered form of pancreatitis and represents one of the diseases of the pancreas which can be cured and healed medically. International consensus diagnostic criteria have been developed, and the clinical phenotypes associated with the histopathologic patterns of lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis should be referred to as type 1 and type 2 AIP, respectively. Most importantly, in type 1 AIP, the pancreatic manifestations are associated with other extrapancreatic disorders, resembling an immunoglobulin G4 (IgG4)-related disease. In addition, the pancreas of a patient with AIP is often infiltrated by various types of immune cells; the cluster of differentiation (CD) 4 or CD8 T lymphocytes and IgG4-bearing plasma cells have been found in the pancreatic parenchyma and other involved organs in AIP and factors regulating T-cell function may influence the development of AIP. From a genetic point of view, it has also been reported that DRB1*0405 and DQB1*0401 mutations are significantly more frequent in patients with AIP when compared to those with chronic calcifying pancreatitis, and that only DQB1*0302 had a significant association with the relapse of AIP. Finally, it has been found that the polymorphic genes encoding cytotoxic T lymphocyte-associated antigen 4, a key negative regulator of the T-cell immune response, are associated with AIP in a Chinese population. Even if these data are not concordant, it is possible that physiological IgG4 responses are induced by prolonged antigen exposure and controlled by type 2 helper T cells. We reviewed the current concepts regarding the pathophysiology of this intriguing disease, focusing on the importance of the humoral and cellular immune responses. PMID:24891971
Pezzilli, Raffaele; Pagano, Nico
Autoimmune pancreatitis (AIP) is a recently discovered form of pancreatitis and represents one of the diseases of the pancreas which can be cured and healed medically. International consensus diagnostic criteria have been developed, and the clinical phenotypes associated with the histopathologic patterns of lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis should be referred to as type 1 and type 2 AIP, respectively. Most importantly, in type 1 AIP, the pancreatic manifestations are associated with other extrapancreatic disorders, resembling an immunoglobulin G4 (IgG4)-related disease. In addition, the pancreas of a patient with AIP is often infiltrated by various types of immune cells; the cluster of differentiation (CD) 4 or CD8 T lymphocytes and IgG4-bearing plasma cells have been found in the pancreatic parenchyma and other involved organs in AIP and factors regulating T-cell function may influence the development of AIP. From a genetic point of view, it has also been reported that DRB1*0405 and DQB1*0401 mutations are significantly more frequent in patients with AIP when compared to those with chronic calcifying pancreatitis, and that only DQB1*0302 had a significant association with the relapse of AIP. Finally, it has been found that the polymorphic genes encoding cytotoxic T lymphocyte-associated antigen 4, a key negative regulator of the T-cell immune response, are associated with AIP in a Chinese population. Even if these data are not concordant, it is possible that physiological IgG4 responses are induced by prolonged antigen exposure and controlled by type 2 helper T cells. We reviewed the current concepts regarding the pathophysiology of this intriguing disease, focusing on the importance of the humoral and cellular immune responses.
Pezzilli, Raffaele; Pagano, Nico
Autoimmune biliary disease is an umbrella term that encompasses several distinct entities such as primary sclerosing cholangitis, primary biliary cirrhosis, autoimmune hepatitis and overlap syndromes. The general approach to the diagnosis of these disorders involves investigating symptomatic patients presenting with a cholestatic biochemical profile. Asymptomatic patients are often diagnosed during investigation of other accompanying or discrete diseases. The distinction between the various entities is necessary for directing clinical management in this group of patients with an underlying autoimmune pathophysiology. Goals of management comprise treating symptoms, preventing complications and suppressing the underlying pathogenetic processes. Liver transplantation plays a vital role in the management of this group of patients and has shown a dramatic improvement in outcomes. Medical therapies such as ursodeoxycholic acid have shown mixed effects with excellent outcomes in primary biliary cirrhosis and less impressive results in primary sclerosing cholangitis. In this manuscript we aim to discuss in detail the management of these autoimmune biliary disorders and describe the effects of different therapies on outcomes on the different subsets of patients. PMID:23860242
Imam, Mohamad H; Talwalkar, Jayant A; Lindor, Keith D
Autoimmune disease-the condition in which the body attacks its own tissue-has been an object of public concern recently. Former President George Bush and his wife Barbara both are afflicted with Graves' disease in which the body's own immune system attakcs the thyroid gland. The safety of breast implants was called into question because of evidence that some recipients had developed autoimmune disorders such a rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Women, the media pointed out, have a higher-than-average incidence of many autoimmune disorders. These events suggest the need to know more about what makes the immune system work so well and what makes it go awry. At ORNL's Biology Division, progress is being in understanding the underlying causes of immune disease by studying mice having a disease that causes them to be underdeveloped; to have scaly skin, small ears, and large spleens; to open their eyes late; and to die early. These [open quotes]scurfy[close quotes]mice are helping us better understand the role of the thymus gland in autoimmune disease.
Abstract and Definition Abstract Context Autoimmune hepatitis has diverse features that can delay its diagnosis and the institution of potentially lifesaving corticosteroid therapy. Objective Review the clinical, laboratory, and histologic features of autoimmune hepatitis and promulgate routine application of its codified diagnostic criteria. Data Sources Reference lists and MEDLINE. Study Selection All clinically pertinent published observations that indicate the diversity of manifestations and pitfalls in diagnosis. Data Extraction Findings that had common clinical relevance and the potential to confuse the diagnosis or delay institution of therapy were selected. Data Synthesis Autoimmune hepatitis can present acutely and have histologic features of centrilobular zone 3 inflammation. Many patients may be asymptomatic, but they frequently have severe or advanced disease and typically develop symptoms later. Autoantibodies are reflective of immune-mediated mechanisms, but they are not diagnostic, pathogenic, or even required for the diagnosis. Genetic factors affect susceptibility, clinical phenotype, and treatment outcome, and they may be clues to indigenous etiologic agents. Autoimmune hepatitis can recur or develop de novo after liver transplantation, and it should be considered in all transplanted patients with allograft dysfunction. Diagnostic criteria have been codified, and a scoring system quantifies the strength of the diagnosis and accommodates atypical or deficient features. Conclusion Autoimmune hepatitis is an important diagnosis to consider in all patients with chronic hepatitis of undetermined cause. Definition Autoimmune hepatitis is a nonresolving inflammation of the liver of unknown cause. It is characterized by the presence of interface hepatitis on histologic examination, hypergammaglobulinemia, and autoantibodies. There are no features that are absolutely diagnostic, and the existence of the condition can be established only by recognition of a constellation of compatible features and the exclusion of other diseases. Drug-induced liver diseases, especially those related to minocycline or diclofenac toxicity; hereditary conditions, most notably Wilson disease; chronic viral infections with hepatitis B or C viruses; and the chronic cholestatic disorders of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) must be excluded by appropriate laboratory, serologic, and histologic investigations. The sine qua non of the diagnosis is the presence of interface hepatitis in liver biopsy tissue (Figure 1). Plasma cell infiltration strengthens the histologic diagnosis (Figure 2), but it can occur in other forms of acute and chronic liver disease. Furthermore, the absence of plasma cell infiltration does not preclude the diagnosis. Other histologic features include panacinar (lobular) hepatitis (Figure 3)[1,3] and centrilobular (Rappaport zone 3) necrosis (Figure 4).[3–6] In the latter instance, successive liver tissue examinations have demonstrated transition from the centrilobular zone 3 pattern to the classical pattern of interface hepatitis during the course of the disease. Centrilobular zone 3 necrosis may be an early histologic manifestation of autoimmune hepatitis and provide clues to a toxic, ischemic, or metabolic basis for the condition.
Czaja, Albert J.
Venous thromboembolism (VTE) is major health problem and is sometimes complicated by lethal pulmonary embolism (PE). Disturbances of the coagulation and anticoagulation systems are important risk factors for VTE. Comparative studies suggest that coagulation and innate immunity have a shared evolutionary origin. It is therefore unsurprising that the immune and coagulation systems are linked, with many molecular components being important for both systems. Systemic inflammation modulates thrombotic responses by suppressing fibrinolysis, upregulating procoagulant, and downregulating anticoagulants, and autoimmune disorders such as systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and Behçet’s syndrome have been linked to an increased risk of VTE. Recent reports have further shown that a majority of autoimmune and immune-mediated disorders are linked to an increased risk of venous thrombosis, PE, or VTE. For instance, a Swedish nationwide study found that the risk of PE was increased in the first year after hospitalization for 33 different autoimmune disorders. Especially high risks were noted for several autoimmune diseases such as immune thrombocytopenic purpura, polyarteritis nodosa, polymyositis/dermatomyositis, ulcerative colitis, and SLE. Another study from England, also based on hospitalization data, found that immune-mediated disorders were associated with an increased risk of VTE compared with other medical causes of hospitalization. Multiple mechanisms may operate and disease-specific factors, such as cardiolipin antibodies, have been identified. However, inflammation by itself appears to change the hemostatic balance in a thrombogenic direction. Recent epidemiological studies, together with previous experimental and clinical studies, indicate that autoimmune disorders should not only be viewed as inflammatory disorders, but also hypercoagulable disorders. Research to identify thrombotic risk factors, elucidate the mechanisms involved, and investigate prophylactic regiments is needed. The present review describes the epidemiological, clinical, and experimental evidence for the connection between VTE and autoimmune and immune-mediated disorders.
Zoller, Bengt; Li, Xinjun; Sundquist, Jan; Sundquist, Kristina
Autoimmune disorders, redox balance and gender differences are closely connected. In fact, activation, proliferation and death of cells of different histotype, including blood and vascular cells, are under control of oxidative balance and are key players in autoimmune disease pathogenesis and progression. However, cells from male and female appear characterized by a huge series of differences in terms of reactive oxygen species production and oxidative stress susceptibility. In this review, we briefly summarize the possible implications of the redox state in the onset and progression of autoimmune diseases in a gender perspective. PMID:18599384
Ortona, Elena; Margutti, Paola; Matarrese, Paola; Franconi, Flavia; Malorni, Walter
In this review we want to consider some of the requirements for autoimmune disease to develop and how this may be reproduced in animal models. Besides a genetic predisposition, environmental triggering factors seem to play a central role in the etiology of many autoimmune diseases. In theory, a structural similarity or identity between the host and an invading pathogen might cause the immune system of the host to react not only to the pathogen but also to self-components. However, in order for such a process of molecular mimicry to induce autoimmunity the mechanisms of maintaining tolerance or ignorance to the self-components need to be circumvented. Subsequently, in order to advance autoimmunity to overt autoimmune disease the frequency and avidity of autoaggressive lymphocytes has to be of sufficient magnitude. Intuitively, one would assume that tolerance might be stronger to identical structures than to structures that just share a certain degree of similarity. Self-reactive lymphocytes with high-avidity are more likely to be deleted or functionally silenced by central and/or peripheral tolerance mechanisms. Thus, perfect mimicry between identical structures might fail in inducing autoimmunity because of efficient tolerance mechanisms. In contrast, imperfect mimicry between similar but not identical structures might on one hand circumvent tolerance but on the other hand result in the generation of lymphocytes with only low- to intermediate avidity. Here we examine animal models that use the concept of molecular mimicry as a potential mechanism for inducing or accelerating autoimmunity. We focus on the RIP-LCMV model for type 1 diabetes and the novel cytochrome P450 2D6 (CYP2D6) model for autoimmune hepatitis, which use either identical or similar triggering and target antigens.
Christen, Urs; Hintermann, Edith; Holdener, Martin; von Herrath, Matthias G.
An imbalance of pro-inflammatory and anti-inflammatory cytokines, autoreactive and inflammatory T helper 1 (Th1) cells, and regulatory T (Treg) cells results in the loss of immune tolerance and the subsequent appearance of inflammatory autoimmune diseases. On the other hand, hormones and neuropeptides are endogenous factors controlling the immune homeostasis that have been proposed as therapeutic agents in different autoimmune disorders.
Javier Leceta; Rosa P. Gomariz; Carmen Martinez; Mar Carrión; Alicia Arranz; Yasmina Juarranz
Abstract,This study examined ,the presence of hypersensitivity to dental ,and environmental,metals ,in patients ,with clinical disorders ,complicated with chronic fatigue syndrome. Three groups of patients were examined through medical history, dental examination, and by using a modified test of blast ,transformation ,for metals—MELISA,. The three groups consisted of the following: 22 patients with autoimmune,thyroiditis with orwithout,polyglandular,autoimmune,activation; 28 fatigued patients free
Ivan Sterzl; Jarmila Procházková; Pavlína Hrdá; Jirina Bártová; Petr Matucha; Vera Dm Stejskal
Similar pathophysiological mechanisms within autoimmune diseases have stimulated searches for common genetic roots. Polyautoimmunity is defined as the presence of more than one autoimmune disease in a single patient. When three or more autoimmune diseases coexist, this condition is called multiple autoimmune syndrome (MAS). We analyzed the presence of polyautoimmunity in 1,083 patients belonging to four autoimmune disease cohorts. Polyautoimmunity was observed in 373 patients (34.4%). Autoimmune thyroid disease (AITD) and Sjögren's syndrome (SS) were the most frequent diseases encountered. Factors significantly associated with polyautoimmunity were female gender and familial autoimmunity. Through a systematic literature review, an updated search was done for all MAS cases (January 2006-September 2011). There were 142 articles retrieved corresponding to 226 cases. Next, we performed a clustering analysis in which AITD followed by systemic lupus erythematosus and SS were the most hierarchical diseases encountered. Our results indicate that coexistence of autoimmune diseases is not uncommon and follows a grouping pattern. Polyautoimmunity is the term proposed for this association of disorders, which encompasses the concept of a common origin for these diseases. PMID:22454759
Rojas-Villarraga, Adriana; Amaya-Amaya, Jenny; Rodriguez-Rodriguez, Alberto; Mantilla, Rubén D; Anaya, Juan-Manuel
Similar pathophysiological mechanisms within autoimmune diseases have stimulated searches for common genetic roots. Polyautoimmunity is defined as the presence of more than one autoimmune disease in a single patient. When three or more autoimmune diseases coexist, this condition is called multiple autoimmune syndrome (MAS). We analyzed the presence of polyautoimmunity in 1,083 patients belonging to four autoimmune disease cohorts. Polyautoimmunity was observed in 373 patients (34.4%). Autoimmune thyroid disease (AITD) and Sjögren's syndrome (SS) were the most frequent diseases encountered. Factors significantly associated with polyautoimmunity were female gender and familial autoimmunity. Through a systematic literature review, an updated search was done for all MAS cases (January 2006–September 2011). There were 142 articles retrieved corresponding to 226 cases. Next, we performed a clustering analysis in which AITD followed by systemic lupus erythematosus and SS were the most hierarchical diseases encountered. Our results indicate that coexistence of autoimmune diseases is not uncommon and follows a grouping pattern. Polyautoimmunity is the term proposed for this association of disorders, which encompasses the concept of a common origin for these diseases.
Rojas-Villarraga, Adriana; Amaya-Amaya, Jenny; Rodriguez-Rodriguez, Alberto; Mantilla, Ruben D.; Anaya, Juan-Manuel
The etiology of autoimmune diseases remains largely unknown. Concordance rates in monozygotic twins are lower than 50% while genome-wide association studies propose numerous significant associations representing only a minority of patients. These lines of evidence strongly support other complementary mechanisms involved in the regulation of genes expression ultimately causing overt autoimmunity. Alterations in the post-translational modification of histones and DNA methylation are the two major epigenetic mechanisms that may potentially cause a breakdown of immune tolerance and the perpetuation of autoimmune diseases. In recent years several studies both in clinical settings and experimental models proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically, data support the impact of epigenetic changes in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and other autoimmune diseases, in some cases based on mechanistical observations. We herein discuss what we currently know and what we expect will come in the next future. Ultimately, epigenetic treatments already being used in oncology may soon prove beneficial also in autoimmune diseases.
Meda, Francesca; Folci, Marco; Baccarelli, Andrea; Selmi, Carlo
A 61-year-old female was admitted to our hospital with severe jaundice and anemia. She was diagnosed with severe acute hepatitis secondary to autoimmune hepatitis (AIH) on the basis of positive anti-nuclear antibody titers, high serum IgG levels, and liver biopsy. Autoimmune hemolytic anemia (AIHA) was diagnosed because of the presence of reticulocytosis, decreased haptoglobin, positive direct Coombs test, and erythroid hyperplasia in the bone marrow. Although AIH occurs in association with various immunological disorders, an association with AIHA is rarely reported. We report a rare case of severe AIH associated with AIHA. PMID:24097153
Hanai, Tatsunori; Naiki, Takafumi; Takamatsu, Manabu; Imai, Kenji; Kitagawa, Junichi; Suetsugu, Atsushi; Takai, Koji; Shiraki, Makoto; Shimizu, Masahito; Hirose, Yoshinobu; Tsurumi, Hisashi; Moriwaki, Hisataka
Celiac disease, also known as gluten-sensitive enteropathy and nontropical sprue, is a prevalent autoimmune disorder that is triggered by the ingestion of wheat gluten and related proteins of rye and barley in genetically susceptible individuals. The immune response in celiac disease involves the adaptive, as well as the innate, and is characterized by the presence of anti-gluten and anti-transglutaminase 2
Chiara Briani; Diana Samaroo; Armin Alaedini
Growing evidence suggests that autoantibodies to neuronal or endothelial targets in psychiatric disorders exist and may be pathogenic. This review describes and discusses the possible role of autoantibodies related to the psychiatric manifestations in autoimmune diseases, autoantibodies related to the psychiatric disorders present in post-streptococcal diseases, celiac disease, chronic fatigue syndrome and substance abuse, and autoantibodies related to schizophrenia and autism, disorders now considered of autoimmune origin. PMID:16719797
Margutti, Paola; Delunardo, Federica; Ortona, Elena
Mutations in a number of signaling components in mice can lead to strong autoimmune phenotypes. In some cases, these mutations likely compromise important feedback inhibitory pathways that downregulate antigen receptor signaling. For example, a deficiency of Lyn leads to a severe lupus-like autoimmunity. This autoimmunity may result from loss of a feedback inhibitory pathway in which Lyn phosphorylates CD22, triggering recruitment of the tyrosine phosphatase SHP-1 to the plasma membrane, which then dampens BCR signaling. Loss of Lyn also compromises an inhibitory pathway involving Fc gamma RIIb and SHIP, an inositol phosphatase. Mutation of Fyn exacerbates the autoimmunity caused by loss of Lyn. This may be due in part to a nonimmunological compromise in the integrity of the podocytes in the kidney, which may make the kidneys more susceptible to immune complex-induced damage. Fyn-deficient mice exhibit a number of immunological abnormalities and also exhibit some autoimmunity, although this is less severe than what is seen in Lyn-deficient mice. Recently a gain of function mutation in CD45 that may enhance activity of Src family tyrosine kinases has also been found to cause autoimmune disease, suggesting that the level of Src family tyrosine kinase activity is an important determinant of immune tolerance. Finally, several studies suggest that there is a significant interaction between Src family tyrosine kinases and the Fas pathway that is important for self-tolerance. Although these studies are still at an early stage, it seems clear that alterations in regulators of antigen receptor signaling can contribute to autoimmunity. PMID:12408047
Yu, Calvin C K; Mamchak, Alusha A; DeFranco, Anthony L
Abstract Deubiquitination-mediated regulation is important for homeostatic NF-?B activation. Aberrant NF-?B activation associated with various inflammatory and autoimmune disorders is linked with defects in the deubiquitinase A20. A20 is an important anti-inflammatory molecule that is induced by multiple signals and has numerous targets. Polymorphisms within the A20 locus or its altered expression are thought to contribute in development of autoimmune disorders. Further various studies in mice models underscore the biological importance of A20 in prevention of inflammatory conditions. Dysregulated A20 is also been suggested as a link between prolonged inflammation and cancer by preliminary reports. This review summarizes the existing understanding and focuses on the new developments in the field of A20 biology. These developments highlight the importance of A20 in pathophysiology of autoimmune disorders and its scope as therapeutics and a biomarker. PMID:24673262
Majumdar, Ishani; Paul, Jaishree
Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA), a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a) a lack of statistical power due to relatively small or diffuse exposure cohorts, (b) exposure misclassification, (c) latency of clinical disease, (d) mild or subclinical entities that remain undetected or masked by other pathologies, or (e) effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease.
Pfau, Jean C.; Serve, Kinta M.; Noonan, Curtis W.
Epigenetic mechanisms are essential for normal development and function of the immune system. Similarly, a failure to maintain epigenetic homeostasis in the immune response due to factors including environmental influences, leads to aberrant gene expression, contributing to immune dysfunction and in some cases the development of autoimmunity in genetically predisposed individuals. This is exemplified by systemic lupus erythematosus, where environmentally induced epigenetic changes contribute to disease pathogenesis in those genetically predisposed. Similar interactions between genetically determined susceptibility and environmental factors are implicated in other systemic autoimmune diseases such as rheumatoid arthritis and scleroderma, as well as in organ specific autoimmunity. The skin is exposed to a wide variety of environmental agents, including UV radiation, and is prone to the development of autoimmune conditions such as atopic dermatitis, psoriasis and some forms of vitiligo, depending on environmental and genetic influences. Herein we review how disruption of epigenetic mechanisms can alter immune function using lupus as an example, and summarize how similar mechanisms may contribute to other human autoimmune rheumatic and skin diseases.
STRICKLAND, FAITH M.; RICHARDSON, BRUCE C.
Mastitis is a substantial clinical problem in lactating women that may result in severe pain and abrupt termination of breastfeeding, thereby predisposing infants to long-term health risks. Many cases of mastitis involve no known infectious agent and may fundamentally be due to autoimmune-mediated inflammation of the breast. Herein, we develop a murine model of autoimmune mastitis and provide a detailed characterization of its resulting phenotype of breast failure and lactation insufficiency. To generate breast-specific autoimmunity, we immunized SWXJ mice with recombinant mouse ?-lactalbumin, a lactation-dependent, breast-specific differentiation protein critical for production of lactose. Mice immunized with ?-lactalbumin showed extensive T-cell–mediated inflammation in lactating normal breast parenchyma but none in nonlactating normal breast parenchyma. This targeted autoimmune attack resulted in breast failure characterized by lactation insufficiency and decreased ability to nurture offspring. Although immunization with ?-lactalbumin had no effect on fertility and birth numbers, pups nursed by ?-lactalbumin–immunized mice showed significantly disrupted growth often accompanied by kwashiorkor-like nutritional abnormalities, including alopecia, liver toxicity, and runting. This experimental model of autoimmune breast failure has useful applications for prophylactic breast cancer vaccination and for addressing inflammatory complications during breastfeeding. In addition, this model is suited for investigating nutritionally based “failure-to-thrive” issues, particularly regarding the long-term implications of postnatal nutritional deprivation.
Kesaraju, Pavani; Jaini, Ritika; Johnson, Justin M.; Altuntas, Cengiz Z.; Gruden, Jessica J.; Sakalar, Cagri; Tuohy, Vincent K.
It is well-known that autoimmunity is significantly more prevalent in females. Growing evidence indicates that genes located\\u000a on the X chromosome may play a role in autoimmunity and immune dysregulation, as also indicated by the frequent association\\u000a of autoimmune phenomena in patients with X-linked primary immune deficiencies (PIDs). Hence, this group of genetic disorders\\u000a is of particular interest to study
Itai M. Pessach
Diabetes mellitus is a common autoimmune endocrine disorder associated with organ-specific autoantibodies which are frequently\\u000a detected at the time of diagnosis. Some of these antibodies are specific to the pancreas (GAD, IA2, ICA) while others are\\u000a related to different autoimmune diseases. Aim of the study: To define the prevalence of thyroid autoimmune disease in Libyan patients with type 1 diabetes
Millad Ghawil; Elio Tonutti; Sulieman Abusrewil; Daniela Visentini; Ibtisam Hadeed; Valeria Miotti; Paolo Pecile; Amel Morgham; Alfred Tenore
Autoimmune Addison disease is a rare autoimmune disorder with symptoms that typically develop over months or years. Following the development of serum autoantibodies to the key steroidogenic enzyme, 21-hydroxylase, patients have a period of compensated or preclinical disease, characterized by elevations in adrenocortocotropic hormone and renin, before overt, symptomatic adrenal failure develops. We propose that local failure of steroidogenesis, causing breakdown of tolerance to adrenal antigens, might be a key factor in disease progression. The etiology of autoimmune Addison disease has a strong genetic component in man, and several dog breeds are also susceptible. Allelic variants of genes encoding molecules of both the adaptive and innate immune systems have now been implicated, with a focus on the immunological synapse and downstream participants in T lymphocyte antigen-receptor signaling. With the exception of MHC alleles, which contribute to susceptibility in both human and canine Addison disease, no major or highly penetrant disease alleles have been found to date. Future research into autoimmune Addison disease, making use of genome-wide association studies and next-generation sequencing technology, will address the gaps in our understanding of the etiology of this disease. PMID:22290360
Mitchell, Anna L; Pearce, Simon H S
The aim of this study was to determine if the prevalence of autoimmune disorders in the relatives of patients with systemic lupus erythematosus (SLE) is greater than that of relatives of patients with juvenile rheumatoid arthritis (JRA). Interviews were used to obtain histories of the following autoimmune disorders among living or deceased first-, second-, and third-degree relatives of 91 SLE
Chun-Mei Huang; Yao-Hsu Yang; Bor-Luen Chiang
Vitamin D acts at several levels in the immune systems to maintain immune tolerance. Vitamin D deficiency is a plausible environmental risk factor for autoimmune disease. Basic, genetic and epidemiological studies indicate a potential role of vitamin D in the prevention and the treatment of autoimmune diseases. Most of the epidemiological studies are cross-sectional, so that they are insufficient to establish a direct link between vitamin D deficiency and both disease risk and disease activity. Randomized, controlled trials are necessary. PMID:24051163
Schoindre, Yoland; Benveniste, Olivier; Costedoat-Chalumeau, Nathalie
Autoimmune conditions are associated with an elevated risk of lymphoproliferative malignancies, but few studies have investigated the risk of myeloid malignancies. From the US Surveillance Epidemiology and End Results (SEER)-Medicare database, 13?486 myeloid malignancy patients (aged 67+ years) and 160?086 population-based controls were selected. Logistic regression models adjusted for gender, age, race, calendar year and number of physician claims were used to estimate odds ratios (ORs) for myeloid malignancies in relation to autoimmune conditions. Multiple comparisons were controlled for using the Bonferroni correction (P<0.0005). Autoimmune conditions, overall, were associated with an increased risk of acute myeloid leukaemia (AML) (OR 1.29) and myelodysplastic syndrome (MDS, OR 1.50). Specifically, AML was associated with rheumatoid arthritis (OR 1.28), systemic lupus erythematosus (OR 1.92), polymyalgia rheumatica (OR 1.73), autoimmune haemolytic anaemia (OR 3.74), systemic vasculitis (OR 6.23), ulcerative colitis (OR 1.72) and pernicious anaemia (OR 1.57). Myelodysplastic syndrome was associated with rheumatoid arthritis (OR1.52) and pernicious anaemia (OR 2.38). Overall, autoimmune conditions were not associated with chronic myeloid leukaemia (OR 1.09) or chronic myeloproliferative disorders (OR 1.15). Medications used to treat autoimmune conditions, shared genetic predisposition and/or direct infiltration of bone marrow by autoimmune conditions, could explain these excess risks of myeloid malignancies.
Anderson, L A; Pfeiffer, R M; Landgren, O; Gadalla, S; Berndt, S I; Engels, E A
Autoimmune diseases comprise a group of about 85 heterogeneous conditions that can affect virtually any organ and tissue in the body. Many autoimmune diseases change significantly during pregnancy: some ameliorate, some worsen, and others are unaffected. Two autoimmune diseases present prominently in relation to pregnancy: postpartum autoimmune thyroiditis and autoimmune hypophysitis. This article will review the current state of knowledge of the immunological changes that occur during normal pregnancy, and will explore the striking temporal association with pregnancy observed in thyroiditis and hypophysitis. PMID:19539059
Landek-Salgado, Melissa A; Gutenberg, Angelika; Lupi, Isabella; Kimura, Hiroaki; Mariotti, Stefano; Rose, Noel R; Caturegli, Patrizio
Connective tissue diseases (CTDs) are a heterogeneous group of disorders that share certain clinical presentations and a disturbed immunoregulation, leading to autoantibody production. Subclinical or overt renal manifestations are frequently observed and complicate the clinical course of CTDs. Alterations of kidney function in Sjögren syndrome, systemic scleroderma (SSc), auto-immune myopathies (dermatomyositis and polymyositis), systemic lupus erythematosus (SLE), antiphospholipid syndrome nephropathy (APSN) as well as rheumatoid arthritis (RA) are frequently present and physicians should be aware of that. In SLE, renal prognosis significantly improved based on specific classification and treatment strategies adjusted to kidney biopsy findings. Patients with scleroderma renal crisis (SRC), which is usually characterized by severe hypertension, progressive decline of renal function and thrombotic microangiopathy, show a significant benefit of early angiotensin-converting-enzyme (ACE) inhibitor use in particular and strict blood pressure control in general. Treatment of the underlying autoimmune disorder or discontinuation of specific therapeutic agents improves kidney function in most patients with Sjögren syndrome, auto-immune myopathies, APSN and RA. In this review we focus on impairment of renal function in relation to underlying disease or adverse drug effects and implications on treatment decisions.
The knowledge of immune dysregulation and autoimmunity in neurological disorders has expanded considerably in recent times. Recognition of clinical syndromes, reliable methods of diagnosis, and early targeted immunotherapy can lead to a favourable outcome in acute and subacute neurological disorders that may be associated with significant morbidity and mortality if left untreated. This review focuses on the rapidly expanding field of autoimmune encephalitis. We describe the differences between limbic encephalitis associated with antibodies targeting intracellular antigens, and neuronal surface antibody syndromes (NSAS) where the antigens are primarily receptors or synaptic proteins located on the neuronal cell surface. We chronologically highlight important developments in NSAS by focusing on voltage gated potassium channel complex-associated antibody mediated encephalitis, anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, and anti-dopamine 2 receptor antibody-associated basal ganglia encephalitis. Contentious issues such as the complexities of using serum antibodies as biomarkers, the initiation of central nervous system autoimmunity, and possible pathogenic mechanisms of these antibodies will be reviewed. The therapeutic challenges that clinicians face such as the timing of therapy and the role of second-line therapy will be discussed, with crucial concepts highlighted in the form of clinical vignettes. Future directions will involve the identification of novel antigens and methods to establish their pathogenicity, as well as evaluation of the most efficacious therapeutic strategies in patients with established NSAS. PMID:24246947
Ramanathan, Sudarshini; Mohammad, Shekeeb S; Brilot, Fabienne; Dale, Russell C
SUMMARY Type 1 diabetes is an autoimmune disorder leading to loss of pancreatic ?-cells and insulin secretion, followed by insulin dependence. Islet and whole pancreas transplantation restore insulin secretion. Pancreas transplantation is often performed together with a kidney transplant in patients with end-stage renal disease. With improved immunosuppression, immunological failures of whole pancreas grafts have become less frequent and are usually categorized as chronic rejection. However, growing evidence indicates that chronic islet autoimmunity may eventually lead to recurrent diabetes, despite immunosuppression to prevent rejection. Thus, islet autoimmunity should be included in the diagnostic work-up of graft failure and ideally should be routinely assessed pretransplant and on follow-up in Type 1 diabetes recipients of pancreas and islet cell transplants. There is a need to develop new treatment regimens that can control autoimmunity, as this may not be effectively suppressed by conventional immunosuppression.
Pugliese, Alberto; Reijonen, Helena K; Nepom, Jerry; Burke, George W
Autoimmune hemolytic anemia (AIHA) is a well known complication of chronic lymphocytic leukemia (CLL). Steroids are the first line of treatment and there are limited effective treatment options for steroid refractory AIHA of CLL. Rituximab, an active agent against B cell malignancies, has also been noted to be active in certain autoimmune hematologic disorders. We used a combination of rituximab,
N Gupta; S Kavuru; D Patel; D Janson; N Driscoll; S Ahmed; KR Rai
BACKGROUND: Autoimmune diseases are disorders caused by an immune response directed against the body's own organs, tissues and cells. In practice more than 80 clinically distinct diseases, among them systemic lupus erythematosus and rheumatoid arthritis, are classified as autoimmune diseases. Although their etiology is unclear these diseases share certain similarities at the molecular level i.e. susceptibility regions on the chromosomes
Thomas Karopka; Juliane Fluck; Heinz-theodor Mevissen; Änne Glass
The identification of two transcription factors that, when mutated, are responsible for severe autoimmune disease in humans is leading to a better understanding of the fundamental processes involved in T-cell tolerance. Both AIRE and FOXP3, identified initially via their association with genetically manipulated mice, are critically involved in tolerance induction in humans. Although mutations in these genes may cause rare
Fred Ramsdell; Steven F Ziegler
To ascertain the strength of the association between thyroid autoimmunity and miscarriage, we per- formed a meta-analysis of both case - control and longitudinal studies performed since 1990 when this association was first described. A clear association between the presence of thyroid antibodies and miscarriage was found with an odds ratio (OR) of 2.73 (95 % confidence interval (CI), 2.20
Mark F Prummel; Wilmar M Wiersinga
Neuronal nicotinic AChRs (nAChRs) are implicated in the pathogenesis of diverse neurological disorders and in the regulation of small-cell lung carcinoma growth. Twelve subunits have been identified in vertebrates, and mutations of one are recognized in a rare form of human epilepsy. Mice with genetically manipulated neuronal nAChR subunits exhibit behavioral or autonomic phenotypes. Here, we report the first model of an acquired neuronal nAChR disorder and evidence for its pertinence to paraneoplastic neurological autoimmunity. Rabbits immunized once with recombinant ?3 subunit (residues 1–205) develop profound gastrointestinal hypomotility, dilated pupils with impaired light response, and grossly distended bladders. As in patients with idiopathic and paraneoplastic autoimmune autonomic neuropathy, the severity parallels serum levels of ganglionic nAChR autoantibody. Failure of neurotransmission through abdominal sympathetic ganglia, with retention of neuronal viability, confirms that the disorder is a postsynaptic channelopathy. In addition, we found ganglionic nAChR protein in small-cell carcinoma lines, identifying this cancer as a potential initiator of ganglionic nAChR autoimmunity. The data support our hypothesis that immune responses driven by distinct neuronal nAChR subtypes expressed in small-cell carcinomas account for several lung cancer–related paraneoplastic disorders affecting cholinergic systems, including autoimmune autonomic neuropathy, seizures, dementia, and movement disorders.
Lennon, Vanda A.; Ermilov, Leonid G.; Szurszewski, Joseph H.; Vernino, Steven
Several studies have shown that gut bacteria have a role in diabetes in murine models. Specific bacteria have been correlated with the onset of diabetes in a rat model. However, it is unknown whether human intestinal microbes have a role in the development of autoimmunity that often leads to type 1 diabetes (T1D), an autoimmune disorder in which insulin-secreting pancreatic islet cells are destroyed. High-throughput, culture-independent approaches identified bacteria that correlate with the development of T1D-associated autoimmunity in young children who are at high genetic risk for this disorder. The level of bacterial diversity diminishes overtime in these autoimmune subjects relative to that of age-matched, genotype-matched, nonautoimmune individuals. A single species, Bacteroides ovatus, comprised nearly 24% of the total increase in the phylum Bacteroidetes in cases compared with controls. Conversely, another species in controls, represented by the human firmicute strain CO19, represented nearly 20% of the increase in Firmicutes compared with cases overtime. Three lines of evidence are presented that support the notion that, as healthy infants approach the toddler stage, their microbiomes become healthier and more stable, whereas, children who are destined for autoimmunity develop a microbiome that is less diverse and stable. Hence, the autoimmune microbiome for T1D may be distinctly different from that found in healthy children. These data also suggest bacterial markers for the early diagnosis of T1D. In addition, bacteria that negatively correlated with the autoimmune state may prove to be useful in the prevention of autoimmunity development in high-risk children.
Giongo, Adriana; Gano, Kelsey A; Crabb, David B; Mukherjee, Nabanita; Novelo, Luis L; Casella, George; Drew, Jennifer C; Ilonen, Jorma; Knip, Mikael; Hyoty, Heikki; Veijola, Riitta; Simell, Tuula; Simell, Olli; Neu, Josef; Wasserfall, Clive H; Schatz, Desmond; Atkinson, Mark A; Triplett, Eric W
Chronic lymphocytic leukemia is frequently associated with immune disturbances. The relationship between chronic lymphocytic leukemia and autoimmune cytopenias, particularly autoimmune hemolytic anemia and immune thrombocytopenia, is well established. The responsible mechanisms, particularly the role of leukemic cells in orchestrating the production of polyclonal autoantibodies, are increasingly well understood. Recent studies show that autoimmune cytopenia is not necessarily associated with poor prognosis. On the contrary, patients with anemia or thrombocytopenia due to immune mechanisms have a better outcome than those in whom these features are due to bone marrow infiltration by the disease. Moreover, fears about the risk of autoimmune hemolysis following single agent fludarabine may no longer be appropriate in the age of chemo-immunotherapy regimens. However, treatment of patients with active hemolysis may pose important problems needing an individualized and clinically sound approach. The concept that autoimmune cytopenia may precede the leukemia should be revisited in the light of recent data showing that autoimmune cytopenia may be observed in monoclonal B-cell lymphocytosis, a condition that can only be detected by using sensitive flow cytometry techniques. On the other hand, there is no evidence of an increased risk of non-hemic autoimmune disorders in chronic lymphocytic leukemia. Likewise, there is no epidemiological proof of an increased risk of chronic lymphocytic leukemia in patients with non-hemic autoimmunity. Finally, since immune disorders are an important part of chronic lymphocytic leukemia, studies aimed at revealing the mechanisms linking the neoplastic and the immune components of the disease should help our understanding of this form of leukemia.
Hodgson, Kate; Ferrer, Gerardo; Montserrat, Emili; Moreno, Carol
Immune Deficiency Disorders:; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorder:; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome
Generalized vitiligo is an autoimmune disorder in which acquired white patches of skin and overlying hair result from autoimmune loss of melanocytes from involved areas. Although usually sporadic, family clustering of vitiligo may occur, in a non-Mendelian pattern typical of multifactorial, polygenic inheritance. Sporadic vitiligo is associated with autoimmune thyroid disease, pernicious anemia, Addison's disease, and lupus; these same disorders occur at increased frequency in patients' first-degree relatives. Here, we studied 133 'multiplex' generalized vitiligo families, with multiple affected family members. The age of onset of vitiligo is earlier in these 'multiplex' families than in patients with sporadic vitiligo. Affected members of the multiplex vitiligo families have elevated frequencies of autoimmune thyroid disease, rheumatoid arthritis, psoriasis, adult-onset insulin-dependent diabetes mellitus, pernicious anemia, and Addison's disease. Probands' unaffected siblings have elevated frequencies of most of these same autoimmune diseases, particularly if the proband had non-vitiligo autoimmune disease. Familial generalized vitiligo is thus characterized by earlier disease onset and a broader repertoire of associated autoimmune diseases than sporadic vitiligo. This mostly likely reflects a greater inherited genetic component of autoimmune susceptibility in these families. These findings have important implications for autoimmune disease surveillance in families in which multiple members are affected with vitiligo. PMID:16029422
Laberge, Greggory; Mailloux, Christina M; Gowan, Katherine; Holland, Paulene; Bennett, Dorothy C; Fain, Pamela R; Spritz, Richard A
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.
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
Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio
Autoimmune disorders are a complex and varied group of diseases that are caused by breakdown of self-tolerance. The aetiology of autoimmunity is multi-factorial, with both environmental triggers and genetically determined risk factors. In recent years, it has been increasingly recognized that genetic risk factors do not act in isolation, but rather the combination of individual additive effects, gene–gene interactions and gene–environment interactions determine overall risk of autoimmunity. The importance of gene–gene interactions, or epistasis, has been recently brought into focus, with research demonstrating that many autoimmune diseases, including rheumatic arthritis, autoimmune glomerulonephritis, systemic lupus erythematosus and multiple sclerosis, are influenced by epistatic interactions. This review sets out to examine the basic mechanisms of epistasis, how epistasis influences the immune system and the role of epistasis in two major autoimmune conditions, systemic lupus erythematosus and multiple sclerosis.
Rose, Anna M; Bell, Lucy C K
Autoimmune neutropenias (AIN) in adults are a heterogeneous group of diseases with clinical manifestations varying from being asymptomatic to having infectious complications with considerable morbidity and mortality. They are characterized by autoantibodies directed against neutrophils, resulting in destruction of neutrophils. AIN can be divided into two forms. In primary AIN, neutropenia is usually the sole hematologic abnormality and it is more common in children. Secondary AIN, which is more prevalent in adults, is associated with underlying autoimmune diseases, malignancies, infections, particularly viral, neurological diseases or drug exposure. This article is an overview of these conditions with emphasis on secondary AIN; it also discusses the available serological methods for antibody detection and recent therapeutic developments including colony stimulating factors, rituximab and Campath-1H. PMID:19293004
Akhtari, Mojtaba; Curtis, Brian; Waller, Edmund K
Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features, hyperglobulinemia (IgG), and the presence of circulating autoantibodies, as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years, a couple of new insights into the genetic aspects, clinical course and treatment of AIH have been reported, which will be the focus of this review. In particular, we concentrate on genome-wide microsatellite analysis, a novel mouse model of AIH, the evaluation of a large AIH cohort for overlap syndromes, suggested novel criteria for the diagnosis of AIH, and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil.
Teufel, Andreas; Galle, Peter R; Kanzler, Stephan
BAFF and APRIL are TNF-like cytokines that support survival and differentiation of B cells. The early appreciation that overexpression of BAFF leads to B cell expansion and a lupus-like syndrome in mice, and the demonstration that BAFF inhibition delays lupus onset in spontaneous mouse models of SLE and other autoimmune diseases has rapidly led to the development of strategies for inhibiting both BAFF and APRIL. The commercialization of this new class of drugs has proceeded in parallel with the continuing elucidation of the biology of the cytokines and their receptors. Recent studies have uncovered a role for BAFF in enhancing both innate and adaptive immune responses and in amplifying aberrant pathways that arise during inflammation. Two phase III studies of an anti-BAFF antibody have yielded positive, although modest, results in SLE and alternate inhibitors are being tested in a variety of autoimmune diseases in which BAFF may play a pathogenic role.
Transplant complications and autoimmune diseases are primarily caused by T-cell immune responses against normal host tissue or transplanted tissues. Current treatment for these disorders is oftentimes not effective, and is typically associated with significant side effects, including global immune suppression.
Fas (also known as Apo1 and CD95) is a cell surface receptor involved in apoptotic cell death. Fas expression and function were analyzed in three children (including two siblings) with a lymphoproliferative syndrome, two of whom also had autoimmune disorders. A large deletion in the gene encoding Fas and no detectable cell surface expression characterized the most affected patient. Clinical
F. Rieux-Laucat; F. Le Deist; C. Hivroz; I. A. G. Roberts; K. M. Debatin; A. Fischer; J. P. de Villartay
Summary Six types of autoimmune hemolytic anemias have been described. Table 1 provides summary highlights for each type of AIHA.\\u000a WAIHA accounts for the majority of cases, followed by CAIHA and DIAHA. In recent years, AIHA status post-BMT has been noted\\u000a to occur more often than previously reported, particularly in T-cell-depleted graft recipients. The clinical presentation\\u000a is diverse among the various
Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.
Kanatsuna, Norio; Papadopoulos, George K.; Moustakas, Antonis K.; Lenmark, Ake
Necrotizing autoimmune myopathies are included in the spectrum of inflammatory myopathies, together with polymyosis, dermatopolymyosis and inclusion body myositis, despite the characteristic feature of marked muscular necrosis without inflammatory infiltrates. The clinical presentation is highly variable, often similar to the other inflammatory myopathies. The most common finding is nevertheless the severe form with rhabdomyolysis. The creatine kinase level is elevated (around 10,000IU/l) and electromyography shows myopathic changes with increased spontaneous activities reflecting the importance of the muscular necrosis. Muscle biopsy is required for diagnosis, revealing active necrosis of the muscle fibers without inflammatory invasion by CDA+ or CD8+ T-cells. Deposition of a microvascular membrane attack complex (C5b9) is often noted, whereas the upregulation of MHC class 1 is rarely detected. Signs of endomysial microangiopathy are frequently reported. Necrotizing autoimmune myopathies can be associated with antisignal recognition particle (SRP) antibodies or more rarely with the usual inflammatory myopathy antibodies. Paraneoplasic forms are described but remain exceptional. Lastly, necrotizing autoimmune myopathies, sometimes associated with statin therapy, have been recently described. They are linked with an antibody directed against 3-hydroxy-3-methyglutaryl-coenzyme A. Treatment is based on corticosteroid therapy, immunosuppressive drugs or intravenous immunoglobulins. Response is variable, depending on the clinical form. PMID:23999024
Petiot, P; Choumert, A; Hamelin, L; Devic, P; Streichenberger, N
Autoimmune pancreatitis (AIP) was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-?-globulinaemia, and antinuclear antibody (ANA) positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis.
Smyk, Daniel S.; Rigopoulou, Eirini I.; Koutsoumpas, Andreas L.; Kriese, Stephen; Burroughs, Andrew K.; Bogdanos, Dimitrios P.
Background. Antinuclear antibodies (ANA) are a hallmark of many autoimmune diseases and can be detected many years before disease onset. Autoimmune thyroid diseases (AITD) are frequently associated with other organ- and non-organ-specific autoimmune disorders. Objectives. To assess the prevalence of ANA in pediatric patients with AITD and their clinical correlations. Methods. Ninety-three consecutive pediatric patients with AITD were enrolled (86 children with chronic lymphocytic thyroiditis and 7 with Graves' disease). ANA, anti-double DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen (anti-ENA), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) was obtained. Signs and symptoms potentially related to rheumatic diseases in children were investigated by a questionnaire. Results. ANA positivity was found in 66/93 children (71%), anti-ENA in 4/93 (4.3%), anti-dsDNA in 1/93 (1.1%), RF in 3/93 (3.2%), and anti-CCP in none. No significant differences were found between the ANA-positive and ANA-negative groups with respect to age, sex, L-thyroxine treatment, or prevalence of other autoimmune diseases. Overall, parental autoimmunity was found in 23%. Conclusions. ANA positivity was demonstrated in 71% of children with AITD. ANA positivity was not related to overt immune-rheumatic diseases. However, because the positivity of ANA can occur even many years before the onset of systemic autoimmune diseases, prospective studies are warranted.
Segni, Maria; Pucarelli, Ida; Truglia, Simona; Turriziani, Ilaria; Serafinelli, Chiara; Conti, Fabrizio
Fibromyalgia and chronic widespread pain syndromes are among the commonest diseases seen in rheumatology practice. Despite advances in the management of these conditions, they remain significant causes of morbidity and disability. Autoimmune thyroid disease is the most prevalent autoimmune disorder, affecting about 10 % of the population, and is a recognized cause of fibromyalgia and chronic widespread pain. Recent reports are shedding light on the mechanisms of pain generation in autoimmune thyroid disease-associated pain syndromes including the role of inflammatory mediators, small-fiber polyneuropathy, and central sensitization. The gradual elucidation of these pain pathways is allowing the rational use of pharmacotherapy in the management of chronic widespread pain in autoimmune thyroid disease. This review looks at the current understanding of the prevalence of pain syndromes in autoimmune thyroid disease, their likely causes, present appreciation of the pathogenesis of chronic widespread pain, and how our knowledge can be used to find lasting and effective treatments for the pain syndromes associated with autoimmune thyroid disease. PMID:24435355
Ahmad, Jowairiyya; Tagoe, Clement E
Mammalian immune responses are intended to eradicate microbial pathogens and thus protect individuals from the harmful effects of such infections. However, unresolved inflammation can be devastating to the host and cause tissue damage and organ malfunction. Immune responses can even mistakenly target self-antigens and mediate autoimmune inflammation. Consequently, a variety of cellular and molecular mechanisms have evolved to control the inflammatory responses, and many of these safeguards or triggers are perturbed in the setting of autoimmunity. In this review, we discuss the emerging roles of cellular non-coding RNAs, and in particular microRNAs (miRNAs), in the regulation of autoimmune inflammation. How miRNAs function to impact the onset, magnitude, and resolution of inflammatory responses and recent observations regarding links between miRNAs and specific autoimmune disorders will be addressed. Finally, the diagnostic and therapeutic relevance of miRNAs involved in autoimmunity will be considered. It is clear that, taken together, mammalian miRNAs are integral to the pathogenesis of mammalian autoimmune diseases and may be effective targets of next-generation therapeutics aimed at eradicating tissue inflammation.
Vulvitis circumscripta plasmacellularis (Zoon's vulvitis) is a distinct clinicopathological entity which presents as a shiny, atrophic, erythematous plaque of the vulva. It is an idiopathic condition with characteristic clinical and histological findings that generally occur in isolation of other medical disorders. We report a 36-year-old woman with vulvitis circumscripta plasmacellularis associated with polyglandular endocrine failure and circulating autoimmune antibodies. The association between Zoon's vulvitis and these autoimmune conditions raises the possibility that Zoon's vulvitis may be an autoimmune disorder. PMID:8977726
Salopek, T G; Siminoski, K
Coinhibitory molecules such as CTLA-4, PD-1 and BTLA negatively regulate immune responses. Multiple studies indicate that the deficiency or mutation of coinhibitory molecules leads to the development of autoimmune diseases in mice and humans, indicating that the negative signals from coinhibitory molecules are crucial for the prevention of autoimmunity. In some conditions, the administration of decoy coinhibitory receptors (e.g., CTLA-4?Ig) or mAb against coinhibitory molecules suppresses the responses of self-reactive T cells in autoimmune diseases. Therefore, modulation of coinhibitory signals seems to be an attractive approach to induce tolerance in autoimmune diseases in humans where the disease-inducing self-antigens are not known. Particularly, administration of CTLA-4?Ig has shown great promise in animal models of autoimmune diseases and has been gaining increasing attention in clinical investigation in several autoimmune diseases in humans.
Watanabe, Norihiko; Nakajima, Hiroshi
Paraneoplastic pemphigus (PNP), a clinically and immunopathologically distinct mucocutaneous blistering dermatosis, is a severe form of autoimmune multiorgan syndrome generally associated with poor therapeutic outcome and high mortality. This IgG-mediated disease is initiated by an obvious or occult lymphoproliferative disorder in most cases. Clinically severe mucositis, and polymorphic blistering skin eruptions, and histologically acantholysis, keratinocyte necrosis and interface dermatitis are its hallmark features. A 58-year-old female presented with recurrent, severe, recalcitrant stomatitis and widespread erosions/blistering lesions of one-year duration. Treatment with repeated courses of systemic corticosteroids at a peripheral center would provide temporary relief. She also had fever, productive cough, odynophagia and poor oral intake, herpes zoster ophthalmicus, pain in the abdomen, and watery diarrhea. An array of investigations revealed chronic lymphocytic leukemia (CLL), mediastinal and para-aortic lymphadenopathy, bronchiolitis obliterans, and vertebral osteoporosis/fractures. With the diagnosis of CLL-associated PNP she was managed with dexamethasone-cyclophosphamide pulse (DCP) therapy for 3 cycles initially, followed by COP regimen (cyclophosphamide, vincristine, and prednisolone) for 5 cycles. Remission is being maintained with chlorambucil and prednisolone pulse therapy once in 3 weeks with complete resolution of skin lesions and adequate control of CLL.
Mahajan, Vikram K.; Sharma, Vikas; Chauhan, Pushpinder S.; Mehta, Karaninder S.; Sharma, Anju Lath; Abhinav, C.; Khatri, Gayatri; Prabha, Neel; Sharma, Saurabh; Negi, Muninder
Autoimmune cytopaenia is a rare, but severe complication after solid organ transplantation. We retrospectively analysed 57 paediatric intestinal transplants performed in 49 patients between 1999 and 2009. Autoimmune cytopaenia was observed in six patients; it appeared after an average of 10 months post-transplant. Warm autoimmune haemolytic anaemia was developed in three patients, cold autoimmune haemolytic anaemia in one and two presented a mixed type. Incidence and causes for haematological cytopaenia such as the following were investigated: immunosuppression, major blood mismatch, viral infection, malignancy, passenger lymphocyte syndrome and lymphoproliferative disorders. Initial treatment included high-dose steroids, intravenous immunoglobulin, plasmapheresis and maintenance of body temperature above 37°C in those with cold autoantibodies. Inclusion of the spleen in multivisceral transplants seems to be an important risk factor. All patients, except one, relapsed after classic therapy, requiring additional treatments. Sirolimus conversion was performed in four patients. One died after infection. The immunosuppressive therapies associated with other concomitant factors, such as viral infections, lymphoproliferative disorders, graft-versus-host disease, passenger lymphocyte syndrome and the inclusion of the spleen as part of multivisceral graft seem to play an important part in the development of autoimmune processes after intestinal transplantation. Therapy is not well established, especially in those resistant to first-line treatment. PMID:20444240
Botija, Gonzalo; Ybarra, Marta; Ramos, Esther; Molina, Manuel; Sarría, Jesús; Martínez-Ojinaga, Eva; Andrés, Ane Miren; López-Santamaría, Manuel; Prieto, Gerardo
Biological therapies directed at proinflammatory cytokines have irrevocably changed the landscape of treatment of rheumatoid arthritis (RA) and other autoimmune diseases. With the advances in our knowledge in cytokine signaling, the question emerges whether targeting intracellular signaling might also be a safe and efficacious strategy. Janus kinases or Jaks are critical for a large family of cytokines and the first Jak inhibitor has been approved by the FDA for the treatment of myelofibrosis. Late phase clinical trials have been completed for another Jakinib in RA. It is therefore timely to consider this new category of drugs and reflect on their potential roles, present and future, in the treatment of RA and related disorders.
O'Shea, John J.; Kontzias, Apostolos; Yamaoka, Kunihiro; Tanaka, Yoshiya; Laurence, Arian
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 1 and environmental factors thus must play an important role. We have attempted to carry out a comprehensive review of all the environmental and hormonal risk factors thought to bring about AITD in genetically predisposed individuals. Low birth weight, iodine excess and deficiency, selenium deficiency, parity, oral contraceptive use, reproductive span, fetal microchimerism, stress, seasonal variation, allergy, smoking, radiation damage to the thyroid gland, viral and bacterial infections all play a role in the development of autoimmune thyroid disorders. The use of certain drugs (lithium, interferon-alpha, Campath-1H) also increases the risk of the development of autoimmunity against the thyroid gland. Further research is warranted into the importance of fetal microchimerism and of viral infections capable of mounting an endogenous interferon-alpha response. PMID:15132715
Prummel, Mark F; Strieder, Thea; Wiersinga, Wilmar M
We describe 2 cases of autoimmune lymphoproliferative syndrome (ALPS), which is a rare disorder of auto-immunity, chronic persistent or recurrent lymphadenopathy, splenomegaly, hepatomegaly and hyper gamma globulinemia (1gG, 1gA). Both cases presented in neonatal period which is a rare age of presentation in this disease. A 20 days old female neonate presented with respiratory symptoms which rapidly progressed needing ventilatory support. There was hepatomegaly and no auscultatory findings in the chest. Serial CBCs (complete blood counts) showed persistent leucocytosis with predominant lymphocytosis. Her chest X-ray showed left sided consolidation which responded poorly to antibiotics. Her prompt clinical response to steroids raised the suspicion of autoimmunity and the diagnosis was established after a negative bone marrow examination for leukemia and a positive result for ALPS on flow cytometry. The second case presented with anemia, thrombocytopenia starting in neonatal period followed by persistent lymphadenopathy, hepatosplenomegaly and recurrent infections which responded poorly to antibiotics. Diagnosis was delayed due to low index of suspicion, and finally achieved with multiple radiological studies, histopathology and flow cytometry. PMID:24906264
Naveed, Muhammad; Khamis Butt, Umar Bin; Mannan, Jovaria
The elucidation of the genes leading to selected immune defects has accelerated our understanding of the molecular basis of tolerance in autoimmunity disorders. Mutations in genes of the immune system are known to lead to a catalogue of functional deficits, including loss of activation-induced Fas-mediated apoptosis, an inability to remove self-reactive T and/or B cells and insufficient numbers or functions of regulatory T cells. In most cases, microbial antigen stimulation occurs simultaneously, leading to further inflammatory responses. In each case, probing the molecular pathways involved in these primary immune defects has led to a better understanding of autoimmune diseases in general. While subjects with X-linked agammaglobulinaemia are almost devoid of autoimmune diseases, B cells which are present, but dysfunctional in other defects, lead to a significant incidence of autoimmune disease. Autoimmunity is also particularly common in the antibody deficiency states. Although organ-based autoimmunity also occurs, for unclear reasons the main conditions are immune thrombocytopenia purpura and autoimmune haemolytic anaemia. The common variable immune deficiency subjects most afflicted by these cytopenias are those with specific peripheral blood memory B cell phenotypes. B cells of these subjects have a retained autoimmune potential, lack of somatic hypermutation, profound loss of proliferative potential, accelerated apoptosis and loss of normal Toll-like receptor signalling. Treatment with high-dose immunoglobulin and/or steroids can be helpful, while rituximab provides benefits in the treatment of refractory cytopenias with apparently little risk, even with repeated use, due to ongoing immune globulin therapy.
Rasmussen's disease is an inflammatory, chronic and progressive brain disorder that usually presents with neocortical focal seizures resistant to conventional treatment and culminates in severe deterioration with hemiparesis, cognitive decline and aphasia. Viral infections and antibodies to the GluR3 receptor have been implicated in the physiopathology of this illness and T-cell mediation may play a role in the cerebral inflammatory process. Classical treatment consists of hemispherectomy of various magnitudes depending on cerebral involvement. The association between therapy-resistant epilepsy and autoimmune phenomena due to antibodies against glutamic acid decarboxylase (anti-GAD) have very recently begun to be studied. The discovery of this association led to a new focus and alternative therapies with immunosuppressors, immunoglobulins, steroids and plasmapheresis, alone or in combination, have begun to be tested with variable success. We describe a boy who was diagnosed in the early stages of Rasmussen's syndrome. He tested positive for anti-GAD antibodies and received treatment with immunoglobulins and steroids. After treatment the boy tested negative for anti-GAD antibodies and he remains asymptomatic after ten months. PMID:12882748
Carrillo Herranz, A; Sánchez Pérez, I; Aparicio Meix, J M; Lozano Giménez, C; Roy Arińo, G; Villar Gimerans, L M; Sánchez Muńoz, L
Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. Narcolepsy is caused by the loss of hypocretin (orexin)-producing neurons in the lateral hypothalamus. Evidence, such as a strong association with HLA DQB1*06:02, strongly suggests an autoimmune basis targeting hypocretin neurons. Genome-wide association studies have strengthened the association between narcolepsy and immune system gene polymorphisms, including the identification of polymorphisms in the T cell receptor alpha locus, TNFSF4 (also called OX40L), Cathepsin H (CTSH) the purinergic receptor P2RY11, and the DNA methyltransferase DNMT1. Recently, attention has been raised regarding a spike in cases of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1) in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Europe. How the immune system may be involved in disease initiation and/or progression remains a challenge to researchers. Potential immunological pathways that could lead to the specific elimination of hypocretin producing neurons include molecular mimicry or bystander activation, and are likely a combination of genetic and environmental factors, such as upper airway infections. PMID:23725858
Mahlios, Josh; De la Herrán-Arita, Alberto K; Mignot, Emmanuel
CD22 is a 140-kDa member of the Siglec family of cell surface proteins that is expressed by most mature B-cell lineages. As a co-receptor of the B-cell receptor (BCR), it is known to contribute to the sensitive control of the B-cell response to antigen. Cross-linking of CD22 and the BCR by antigen triggers the phosphorylation of CD22, which leads to activation of signaling molecules such as phosphatases. Signal transduction pathways involving CD22 have been explored in a number of mouse models, some of which have provided evidence that in the absence of functional CD22, B cells have a "hyperactivated" phenotype, and suggest that loss of CD22 function could contribute to the pathogenesis of autoimmune diseases. Modulating CD22 activity has therefore been suggested as a possible therapeutic approach to such diseases. For example, the novel CD22-targeting monoclonal antibody epratuzumab is currently under investigation as a treatment for the connective tissue disorder systemic lupus erythematosus (SLE). PMID:23083346
Dörner, Thomas; Shock, Anthony; Smith, Kenneth G C
A specific and sensitive assay was performed to detect both anti-SS-A\\/Ro, and anti-SS-B\\/La antibodies in sera of patients with autoimmune disease, including systemic lupus erythematosus, (SLE), progressive systemic sclerosis (PSS), Sjögren's syndrome (SS), discoid lupus erythematosus (DLE), mixed connective tissue disease (MCTD), generalized morphea (GM), and dermatomyositis (DM). The SS-A\\/Ro and SS-B\\/La antigens were prepared from human spleen (HSE) and
Y. Inagaki; Y. Jinno; Y. Hamasaki; H. Ueki
Interleukin-33 (IL-33) is a member of the IL-1 cytokine family. It predominantly induces type 2 immune responses and thus is protective against atherosclerosis and nematode infections but contributes to allergic airway inflammation. Interleukin-33 also plays a pivotal role in the development of many autoimmune diseases through mechanisms that are still not fully understood. In this review, we focus on the recent advances in understanding of the expression and function of IL-33 in some autoimmune disorders, aiming to provide insight into its potential role in disease development. PMID:24116703
Pei, Cheng; Barbour, Mark; Fairlie-Clarke, Karen J; Allan, Debbie; Mu, Rong; Jiang, Hui-Rong
Autoimmune and inflammatory uveitis are a group of potentially blinding intraocular inflammatory diseases that arise without a known infectious trigger and are often associated with immunological responses to unique retinal proteins. In the United States, about 10% of the cases of severe visual handicap are attributed to this group of disorders. As I discuss here, experimental models of ocular autoimmunity targeting retinal proteins have brought about a better understanding of the basic immunological mechanisms involved in the pathogenesis of uveitis and are serving as templates for the development of novel therapies.
Caspi, Rachel R.
Autoimmune and inflammatory uveitis are a group of potentially blinding intraocular inflammatory diseases that arise without a known infectious trigger and are often associated with immunological responses to unique retinal proteins. In the United States, about 10% of the cases of severe visual handicap are attributed to this group of disorders. As I discuss here, experimental models of ocular autoimmunity targeting retinal proteins have brought about a better understanding of the basic immunological mechanisms involved in the pathogenesis of uveitis and are serving as templates for the development of novel therapies. PMID:20811163
Caspi, Rachel R
Summary In recent years, active research using genomic, cellular and animal modeling approaches has revealed the fundamental forces driving the development of autoimmune diseases. Type I IFN (IFN) imprints unique molecular signatures in a list of autoimmune diseases. IFN is induced by diverse nucleic acid-containing complexes, which trigger innate immune activation of plasmacytoid dendritic cells (pDCs). IFN primes, activates or differentiates various leukocyte populations to promote autoimmunity. Accordingly, IFN signaling is essential for the initiation and/or progression of lupus in several experimental models. However, the heterogeneous nature of SLE requires better characterization on how IFN pathways are activated and subsequently promote the advancement of autoimmune diseases. Given the central role of type I IFN, various strategies are devised to target these cytokines or related pathways to curtail the progression of autoimmune diseases.
Di Domizio, Jeremy; Cao, Wei
In recent years, active research using genomic, cellular and animal modeling approaches has revealed the fundamental forces driving the development of autoimmune diseases. Type I interferon imprints unique molecular signatures in a list of autoimmune diseases. Interferon is induced by diverse nucleic acid-containing complexes, which trigger innate immune activation of plasmacytoid dendritic cells. Interferon primes, activates or differentiates various leukocyte populations to promote autoimmunity. Accordingly, interferon signaling is essential for the initiation and/or progression of lupus in several experimental models. However, the heterogeneous nature of systemic lupus erythematosus requires better characterization on how interferon pathways are activated and subsequently promote the advancement of autoimmune diseases. Given the central role of type I interferon, various strategies are devised to target these cytokines or related pathways to curtail the progression of autoimmune diseases. PMID:23445195
Di Domizio, Jeremy; Cao, Wei
Although genetics contributes to the development of autoimmune diseases, it is clear that “environmental” factors are also required. These factors are thought to encompass exposure to certain drugs and environmental pollutants. This paper examines the mechanisms that normally maintain immune unresponsiveness in the liver and discusses how exposure to certain xenobiotics such as trichloroethylene may disrupt those mechanisms and promote autoimmune hepatitis.
Gilbert, Kathleen M.
Leukocyte activation, circulation, and localization to inflammatory sites are dependent on adherence to molecules on other cells or to extracellular matrix ligands. Adhesion molecule expression and interactions are probably involved in initiation and propagation of autoimmune diseases. Adhesion molecules pertinent to the development of autoimmunity are the subject of this review. Material in this review was generated by a manual
Robert W. McMurray
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.
Venkatesha, Shivaprasad H.; Rajaiah, Rajesh; Berman, Brian M.; Moudgil, Kamal D.
Sex hormones, especially estrogen and prolactin (PRL), have an important role in modulating the immune response. PRL is secreted from the pituitary gland as well as other organs and cells particularly lymphocytes. PRL has an immune stimulatory effect and promotes autoimmunity. PRL interferes specifically with B cell tolerance induction, enhances proliferative response to antigens and mitogens and increases the production of immune globulins, cytokines and autoantibodies. Hyperprolactinemia (HPRL) in women present with clinical manifestations of galactorrhea, primary or secondary amenorrhea, delayed menarche or a change in the menses either in the amount or in the regularity. Furthermore in the last 2 decades multi-organ and organ specific autoimmune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), Hashimoto's thyroiditis (HT), multiple sclerosis (MS), psoriasis, hepatitis C patients, Behçet's disease, peripartum cardiomyopathy (PPCM) and active celiac disease were discussed to be associated with HPRL. There is data showing correlation between PRL level and diseases activity in few diseases. Genetic factors may have a role in humans as in animal models. The PRL isoforms based on the differences in the amino acid sequence and size of the cytoplasmic domain have an important effect on the bioactivity on prolactin receptors (PRL-Rs). PMID:22155203
Shelly, Shahar; Boaz, Mona; Orbach, Hedi
The Autoimmune Lymphoproliferative Syndrome (ALPS) is an impairment of lymphocyte apoptosis expressed by generalized non-malignant lymphoproliferation, lymphadenopathy and/or splenomegaly. This article describes a seven and 14 year old males. The first one was admitted at 3 years of age with fever, bicytopenia and generalized lymphadenopathy. Hystopathological analysis of lymph nodes showed reactive follicular hyperplasia and marked paracortical expansion. He was readmitted three years later presenting herpes zoster and similar clinical features. High levels of IL-10 and increasing tendency of Fas-L in plasma and serum. The second child was admitted at 13 years of age presenting thigh and gluteus cellulitis, anemia and neutropenia. T lymphocytes aß+CD4-CD8- 3,1%. Hystopathological analysis of lymph nodes showed marked paracortical hyperplasia. Both children are treated with mycophenolate mofetil with good response. ALPS is an underestimated entity that must be considered in non malign lymphoproliferation, autoimmunity and expansion of an unusual population of a/ßCD3+CD4-CD8-(double-negative T cells>1%). PMID:22525637
Rodrigues, Vera; Conde, Marta; Figueiredo, António; Vasconcelos, Júlia; Dias, Alexandra
Summary A number of autoimmune diseases, including multiple sclerosis, are mediated by self-reactive T cells that have escaped the deletional mechanisms of central tolerance. Usually, these T cells are kept at bay through peripheral tolerance mechanisms including regulation through coinhibitory receptors and suppression by regulatory T cells (Tregs). However, if these mechanisms fail, self-reactive T cells are activated and autoimmune responses ensue. This review outlines how the coinhibitory receptors CTLA-4, PD-1, Tim-3 and TIGIT act at different checkpoints to inhibit autoreactive T cells and suppress the development of CNS autoimmunity. Loss of each of these receptors predisposes to autoimmunity, indicating a non-redundant role in maintaining peripheral tolerance. At the same time, their functional patterns seem to overlap to a large degree. We therefore propose that only the concerted action of a combination of inhibitory receptors is able to maintain peripheral tolerance and prevent autoimmunity.
Joller, Nicole; Peters, Anneli; Anderson, Ana C.; Kuchroo, Vijay K.
Common variable immunodeficiency (CVID) is the most common clinically significant primary immune defect. Although the hallmark of CVID is hypogammaglobulinemia, the intrinsic dysregulation of the immune system leads to defective T-cell activation and proliferation, as well as dendritic cell and cytokine defects. Although 70% to 80% of patients have had recurrent sinopulmonary infections, auto-immunity and inflammatory complications are also common. The most common autoimmune conditions are immune thrombocytopenic purpura and hemolytic anemia, but other autoimmune complications arise, including rheumatoid arthritis, pernicious anemia, primary biliary cirrhosis, thyroiditis, sicca syndrome, systemic lupus, and inflammatory bowel disease. Treatment of autoimmunity includes high-dose immunoglobulins, corticosteroids, selected immunosuppressants, and other immune modulators. This review focuses on autoimmune conditions associated with CVID, potential mechanisms of immune dysregulation, and therapeutic strategies.
Agarwal, Shradha; Cunningham-Rundles, Charlotte
The histological hallmark of autoimmune hepatitis (AIH) is a dense portal mononuclear cell infiltrate that invades the surrounding parenchyma and comprises T and B lymphocytes, macrophages, and plasma cells. An unknown but powerful stimulus must be promoting the formation of this massive inflammatory cellular reaction that is likely to initiate and perpetuate liver damage. An autoimmune attack can follow different pathways to inflict damage on hepatocytes. Liver damage is likely to be orchestrated by CD4+ T lymphocytes recognizing an autoantigenic liver peptide. To trigger an autoimmune response, the peptide must be embraced by an HLA class II molecule and presented to naďve CD4+ T helper (Th0) cells by professional antigen presenting cells, with the co-stimulation of ligand-ligand fostering interaction between the two cells. Th0 cells become activated, differentiate into functional phenotypes according to the cytokines prevailing in the microenvironment and the nature of the antigen, and initiate a cascade of immune reactions determined by the cytokines produced by the activated T cells. Th1 cells, arising in the presence of the macrophage-derived interleukin (IL) -12, secrete mainly IL-2 and interferon-gamma (IFN-?), which activate macrophages, enhance expression of HLA classI(increasing liver cell vulnerability to a CD8+ T cell cytotoxic attack), and induce expression of HLA class II molecules on hepatocytes. Th2 cells, which differentiate from Th0 if the microenvironment is rich in IL-4, produce mainly IL-4, IL-10, and IL-13 which favour autoantibody production by B lymphocytes. Physiologically, Th1 and Th2 antagonize each other. Th17 cells, a recently described population, arise in the presence of transforming growth factor beta (TGF-?) and IL-6 and appear to have an important effector role in inflammation and autoimmunity. The process of autoantigen recognition is strictly controlled by regulatory mechanisms, such as those exerted by CD4+CD25+ regulatory T cells, which derive from Th0 in the presence of TGF-?, but in the absence of IL-6. If regulatory mechanisms fail, the autoimmune attack is perpetuated. Over the past three decades different aspects of the above pathogenic scenario have been investigated. In particular, a defect in immunoregulation affecting CD4+CD25+ regulatory T cells (T-regs) has been demonstrated in AIH, particularly at diagnosis or during relapse. Advances in the study of autoreactive T cells have occurred mostly in AIH type 2, since the knowledge that CYP2D6 is the main autoantigen has enabled the characterization of both CD4 and CD8 T cells targeting this cytochrome. CD4 T cells from patients with type 2 AIH positive for the predisposing HLA allele DRB1*0701 recognize seven regions of CYP2D6, five of which are also recognized by CD8 T cells. High numbers of IFN-? producing CD4 T cells and CD8 T cells are associated with biochemical evidence of liver damage, suggesting a combined cellular immune attack.
Vergani, Diego; Mieli-Vergani, Giorgina
Autoimmune hepatitis (AIH) is occasionally triggered by drug treatments. Recently, as biological agents are becoming widely used for autoimmune disorders, there have been a growing number of reports of the development of autoimmune processes related to these agents. A 52-year-old Japanese woman with psoriasis developed liver damage two months after initiation of anti-TNF-? therapy with adalimumab. Liver histological findings were compatible with AIH, and positive conversions of ANAs were detected. The patient was treated with prednisolone and had a good response. While some cases of AIH triggered by anti-TNF-? therapies have been reported, the pathogenesis remains unspecified. When elevation of liver enzymes is observed with high IgG levels and seropositivity of ANA during the course of anti-TNF-? therapy, liver biopsy findings may be essential and important to make definitive diagnosis of AIH.
Autoimmune encephalitis related to voltage-gated potassium channel (VGKC) antibodies can occur as a complication of cancer but, more frequently, as a non-paraneoplastic disorder. The prompt recognition and treatment could mitigate the morbidity associated with this entity, but the broad-spectrum of neurological manifestations often makes the diagnosis a challenge. The authors describe, here, a unique case of autoimmune encephalitis related to VGKC antibodies preceded by an ischaemic stroke. Conditions associated with the stroke (infection, seizures, metabolic disturbances) had delayed the diagnosis. The authors suggest that autoimmune encephalitis needs to be taken into consideration as part of a differential diagnosis in patients with prolonged encephalopathy following an ischaemic stroke. Infection may trigger an inflammatory response. In addition, the rupture of blood brain barrier that occurs in stroke may have a pathogenic role by allowing antibodies to gain access to the central nervous system.
Simal, Patricia; Garcia-Garcia, Ana Maria; Serna-Candel, Carmen; Egido, Jose Antonio
The decline in immunocompetence with age is accompanied by the increase in the incidence of autoimmune diseases. Aging of the immune system, or immunosenescence, is characterized by a decline of both T and B cell function, and paradoxically the presence of low-grade chronic inflammation. There is growing evidence that epigenetics, the study of inherited changes in gene expression that are not encoded by the DNA sequence itself, changes with aging. Interestingly, emerging evidence suggests a key role for epigenetics in human pathologies, including inflammatory and neoplastic disorders. Here, we will review the potential mechanisms that contribute to the increase in autoimmune responses in aging. In particular, we will discuss how epigenetic alterations, especially DNA methylation and histone acetylation, are accumulated during aging and how these events contribute to autoimmunity risk.
Anti-TNFalpha blockers are extensively used in the management of chronic inflammatory disorders. Their administration may be associated with the generation of autoantibodies; this review focuses on the autoimmune phenomena linked to anti-TNFalpha inhibition, on the hypothesized pathogenetic mechanisms and on the clinical implications. While the development of antinuclear and, less frequently, of anti-DNA antibodies is a common finding, the onset of autoimmune diseases during anti-TNFalpha blocker treatment is a rare event, which needs to be promptly recognized in order to plan the appropriate management. Moreover the specific autoantibodies associated with rheumatoid arthritis are considered before and after biotherapy. Similarities and differences among infliximab, etanercept and adalimumab concerning induced autoimmune phenomena are underlined. PMID:19539516
Caramaschi, Paola; Bambara, Lisa Maria; Pieropan, Sara; Tinazzi, Ilaria; Volpe, Alessandro; Biasi, Domenico
Type 1 diabetes (T1D) represents 10 to 15% of all forms of diabetes. Its incidence shows a consistent rise in all countries under survey. Evidence for autoimmunity in human T1D relies on the detection of insulitis, of islet cell antibodies, of activated ?-cell-specific T lymphocytes and on the association of T1D with a restricted set of class II major histocompatibility complex (MHC) alleles. However, mechanisms that initiate the failure of immune tolerance to ?-cell autoantigens remain elusive in common forms of T1D. T1D commonly develop as a multifactorial disease in which environmental factors concur with a highly multigenic background. The disease is driven by the activation of T-lymphocytes against pancreatic ?-cells. Several years elapse between initial triggering of the autoimmune response to ? cells, as evidenced by the appearance or islet cell autoantibodies, and the onset of clinical diabetes, defining a prediabetes stage. Active mechanisms hold back autoreactive effector T-cells in prediabetes, in particular a subset of CD4+ T-cells (T(reg)) and other regulatory T-cells, such as invariant NKT cells. There is evidence in experimental models that systemic or local infections can trigger autoimmune reactions to ?-cells. However, epidemiological observations that have accumulated over years have failed to identify undisputable environmental factors that trigger T1D. Moreover, multiple environmental factors may intervene in the disease evolution and protective as weel as triggering environmental factors may be involved. Available models also indicate that local signals within the islets are required for full-blown diabetes to develop. Many autoantigens that are expressed by ?-cells but also by the other endocrine islet cells and by neurons are recognized by lymphocytes along the development of T1D. The immune image of ?-cells is that of native components of the ?-cell membrane, as seen by B-lymphocytes, and of fragments of intracellular ?-cell proteins in the form of peptides loaded onto class I MHC molecules on the ?-cell surface and class I and class II molecules onto professional antigen presenting cells. Given the key role of T lymphocytes in T1D, the cartography of autoantigen-derived peptides that are presented to class I-restricted CD8(+) T-cells and class II-restricted CD4(+) T-cells is of outmost importance and is a necessary step in the development of diagnostic T-cell assays and of immunotherapy of T1D. PMID:23182678
Vitiligo is more common in people with certain autoimmune diseases. Here we studied the association between vitiligo and autoimmune diseases. In this case control study, 86 patients with vitiligo were questioned about the location of vitiligo, family history, treatment and therapeutic response. All patients were examined both clinically and with laboratory tests to detect the presence of autoimmune disorders including autoimmune thyroid disease, pernicious anemia, insulin dependent diabetes, and Systemic Lupus Erythematic (SLE) and Addison disease. We compared the prevalence of autoimmune disorder in vitiligo patients with that in a group of age-and gender-matched normal population. Average age of disease onset was 21.8 +/- 11 years; 61% of patients were female and 39% were male. The most common locations of vitiligo were hands (33.7%) and face (32.1%). The most common pattern of onset was vulgaris type (40%). Nearly one-fourth of patients had a positive family history of vitiligo. Prevalence of thyroid disorders in vitiligo patients and control group was 21.1 and 7%, respectively. The difference was statistically significant (p = 0.008). The most common autoimmune disorder in patient with vitiligo was hypothyroidism. Family history had a poor prognostic effect on response to therapy. PMID:24494526
Nejad, Shahla Babaee; Qadim, Hamideh Herizchi; Nazeman, Leila; Fadaii, Roohollah; Goldust, Mohamad
Signaling thresholds influence the balance between humoral immunity and autoimmunity. Cell surface CD19 regulates intrinsic and Ag receptor-induced B lymphocyte signaling thresholds, and transgenic mice that overexpress CD19 by 3-fold generate spontaneous autoantibodies in a genetic background not associated with autoimmunity. To quantify the extent that genetically determined differences in expression of a single cell surface molecule can influence autoantibody production, we have assessed autoimmunity in a C57BL/6-transgenic mouse line with subtle 15-29% increases in CD19 cell surface expression (CD19 transgenic). Antinuclear Abs, especially anti-spindle pole Abs, rheumatoid factor, and autoantibodies for ssDNA, dsDNA, and histone were produced in these transgenic mice, but not littermate controls. This demonstrates that small changes in CD19 expression can induce autoantibody production. Remarkably, similar changes in CD19 expression were found on B cells from patients with systemic sclerosis, a multisystem disorder of connective tissue with autoantibody production. CD19 density on blood B cells from systemic sclerosis patients was significantly ( approximately 20%) higher compared with normal individuals, whereas CD20, CD22, and CD40 expression were normal. These results suggest that modest changes in the expression or function of regulatory molecules such as CD19 may shift the balance between tolerance and immunity to autoimmunity. Thereby autoimmune disease may result from a collection of subtle multigenic alterations that could include incremental density changes in cell surface signaling molecules. PMID:11086109
Sato, S; Hasegawa, M; Fujimoto, M; Tedder, T F; Takehara, K
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’. OBJECTIVES: To recognize the overlap syndromes in adults and manage them appropriately. METHODS: The MEDLINE database was reviewed for published experiences from 1984 to 2013. RESULTS: Patients with autoimmune hepatitis may exhibit features of primary biliary cirrhosis (7% to 13%), primary sclerosing cholangitis (6% to 11%) or a cholestatic syndrome without other diagnostic features (5% to 11%). These mixed phenotypes may represent classical autoimmune hepatitis with atypical features, transition states in the evolution of classical cholestatic syndromes, concurrent separate diseases or pathogenically distinct disorders. The ‘Paris criteria’ have been endorsed for the diagnosis of the overlap syndrome with primary biliary cirrhosis, and treatment with conventional immunosuppressive therapy alone or in combination with low-dose ursodeoxycholic acid can be guided by the serum alkaline phosphatase level. The overlap syndrome with primary sclerosing cholangitis or with cholestasis without diagnostic features is commonly treated with immunosuppressive therapy and ursodeoxycholic acid. Responses are variable and commonly incomplete (20% to 100% improvement) depending on the degree of cholestasis. DISCUSSION: The overlap syndromes are clinical descriptions rather than pathological entities, and the dominant component of the disease determines its designation and therapy. Cholestatic findings in autoimmune hepatitis influence the response to immunosuppressive therapy. CONCLUSION: The overlap syndromes must be considered in patients with autoimmune hepatitis and cholestatic findings, concurrent inflammatory bowel disease or steroid-refractory disease.
Czaja, Albert J
Autoimmune thyroid diseases (AITD) are the most common organ-specific autoimmune disorders affecting approximately 5% of the overall population. An aberrant interaction between abnormal thyrocytes, abnormal antigen-presenting cells and abnormal T cells forms the basis for the atypical autoimmune reaction targeting thyroid antigens. It was proposed that nongenetic (environmental and hormonal) factors play a crucial etiological role in AITD development, through altering immune-endocrine interactions. The most outstanding fact is that in genetically predisposed individuals, the disruption of these neuroendocrine-immune interactions by environmental factors results in thyroid autoimmune dysfunction. These interactions are able to incline the balance between Th1-Th2 immune response toward one side, resulting in a Th1-cell-mediated autoimmune reaction with thyrocyte destruction and hypothyroidism in Hashimoto's thyroiditis but to a hyperreactive Th2-mediated humoral response against TSH receptor with stimulatory antibodies leading to Graves' disease hyperthyroidism. In this review the main mechanisms involved are summarized. In this sense, the participation of stress-mediated activation of the sympathoadrenal system and hypothalamic-pituitary-adrenal axis, the hormonal changes occurring during pregnancy and postpartum acting on antigen-presenting cells and influencing, in this way, the balance of the immune status are shown to participate in AITD etiology. The possibility that altered levels of thyroid hormones during the course of the AITD may alter immune function is also discussed. PMID:18667802
Klecha, Alicia Juana; Barreiro Arcos, María Laura; Frick, Luciana; Genaro, Ana María; Cremaschi, Graciela
Apoptosis is a physiological process of self-destruction for cells that are damaged or programmed to die. Apoptosis occurs through a series of regulated events that allow cellular debris to be contained and efficiently phagocytosed without initiating a proinflammatory immune response. Recent data have linked physiological apoptosis and the uptake of apoptotic cells by macrophages and some subsets of dendritic cells to the maintenance of peripheral immune tolerance. However, when cells die through necrosis, spilling their intracellular contents, or are infected with various pathogens, activation of antigen-presenting cells and induction of an immune response can occur. Receptors for extrinsic pathogen-associated structures, such as membrane bound Toll-like receptors (TLRs) or intracellular Nod-like receptors (NLRs) can also respond to cross-reactive host molecules from dying cells and may focus autoimmune responses onto these antigens. Several autoimmune disorders have been linked to defects in the apoptotic process. Defective apoptosis of immune cells leads to autoimmunity, as in autoimmune lymphoproliferative syndrome (ALPS) associated with mutations in the death receptor Fas. Defective clearance of apoptotic cell debris can also lead to autoantibody production. We will discuss how cell death and apoptotic cell clearance may affect the finely tuned balance between peripheral immune tolerance and autoimmunity. PMID:17029966
Viorritto, Irene C B; Nikolov, Nikolay P; Siegel, Richard M
Auto-immune hepatitis is a chronic necroinflammatory liver disorder that is characterized by hypergammaglobulinemia, auto-antibodies in serum, and, on histological examination, the presence of periportal hepatitis. Although it can be associated with a number of other auto-immune diseases, Sjogren's syndrome is rarely associated with auto-immune hepatitis. We herein report an unusual case of auto-immune hepatitis associated with primary Sjogren's syndrome. A 39-year-old woman was admitted to our hospital due to jaundice. Laboratory data showed negative viral hepatitis marker, increased serum IgG level, positive anti- nuclear antibody, and an increased rheumatoid factor titer. The patient had no history of taking medications and alcohol. Based on characteristic clinical features, liver biopsy findings, positive Schirmer's test, and salivary scintigraph, she was diagnosed as having auto-immune hepatitis and Sjogren's syndrome. The patient achieved complete remission with steroid monotherapy. PMID:12657826
Kwon, Yong Dae; Lee, Hong Sik; Park, Chul Hee; Jeen, Yoon Tae; Chun, Hoon Jai; Lee, Sang Woo; Choi, Jai Hyun; Kim, Chang Duck; Ryu, Ho Sang; Hyun, Jin Hai
Experiments with animal models of autoimmune disease provided the rational and stimulus for the current, clinical studies of autologous stem cell transplantation for the treatment of a variety of severe, refractory, autoimmune diseases. The discoveries that led to the recognition of the key role of hematopoietic stem cells and the successful treatment of autoimmune diseases with bone marrow transplants are reviewed. The relevance of spontaneous and induced autoimmune disease models for the development of clinical treatment regimens is discussed. Most of the investigations with autologous stem cell transplantation have been performed with induced autoimmune disorders: in rats with adjuvant arthritis and in rats or mice with experimental, allergic encephalomyelitis, the current model for multiple sclerosis. The main aspects of this translational research were the conditioning regimens and the degree of T cell depletion of the graft as determinants of remission induction and the incidence of relapses. The emerging recommendations are compared with the outcome so far of the clinical studies. PMID:12377928
van Bekkum, D W
Cytokine (receptor) genes have traditionally attracted great interest as plausible genetic risk factors for autoimmune disease. Since 2007, the implementation of genome-wide association studies has facilitated the robust identification of allelic variants in more than 35 cytokine loci as susceptibility factors for a wide variety of over 15 autoimmune disorders. In this review, we catalog the gene loci of interleukin, chemokine, and tumor necrosis factor receptor superfamily and ligands that have emerged as autoimmune risk factors. We examine recent progress made in the clarification of the functional mechanisms by which polymorphisms in the genes coding for interleukin-2 receptor alpha (IL2RA), IL7R, and IL23R may alter risk for autoimmune disease, and discuss opposite autoimmune risk alleles found, among others, at the IL10 locus.
Self tolerance loss is fundamental to autoimmunity. While understanding of immune regulation is expanding rapidly, the mechanisms causing loss of tolerance in most autoimmune diseases remain elusive. Autoimmunity is believed to develop when genetically predisposed individuals encounter environmental agents that trigger the disease. Recent advances in the genetic and environmental contributions to autoimmunity suggest that interactions between genetic elements and
Anura Hewagama; Bruce Richardson
Autoimmune disease results from the action of environmental factors on a predisposed genotype. In this review, the role of genetic susceptibility in the aetiology of autoim- mune disease is examined. As the genetics of autoimmune diabetes has been studied more intensively than that ofother autoimmune diseases, supporting evidence is drawn principally from that example. Autoimmune diseases are not inherited as
Alan G. Baxter
The group A streptococcus, Streptococcus pyogenes, and its link to autoimmune sequelae, has acquired a new level of understanding. Studies support the hypothesis that molecular mimicry between the group A streptococcus and heart or brain are important in directing immune responses in rheumatic fever. Rheumatic carditis, Sydenham chorea and a new group of behavioral disorders called pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections are reviewed with consideration of autoantibody and T cell responses and the role of molecular mimicry between the heart, brain and group A streptococcus as well as how immune responses contribute to pathogenic mechanisms in disease. In rheumatic carditis, studies have investigated human monoclonal autoantibodies and T cell clones for their crossreactivity and their mechanisms leading to valve damage in rheumatic heart disease. Although studies of human and animal sera from group A streptococcal diseases or immunization models have been crucial in providing clues to molecular mimicry and its role in the pathogenesis of rheumatic fever, study of human monoclonal autoantibodies have provided important insights into how antibodies against the valve may activate the valve endothelium and lead to T cell infiltration. Passive transfer of anti-streptococcal T cell lines in a rat model of rheumatic carditis illustrates effects of CD4+ T cells on the valve. Although Sydenham chorea has been known as the neurological manifestation of rheumatic fever for decades, the combination of autoimmunity and behavior is a relatively new concept linking brain, behavior and neuropsychiatric disorders with streptococcal infections. In Sydenham chorea, human mAbs and their expression in transgenic mice have linked autoimmunity to central dopamine pathways as well as dopamine receptors and dopaminergic neurons in basal ganglia. Taken together, the studies reviewed provide a basis for understanding streptococcal sequelae and how immune responses against group A streptococci influence autoimmunity and inflammatory responses in the heart and brain. PMID:24892819
Cunningham, Madeleine W
Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory disorders of unknown etiology characterized by a wide range of abnormalities of the immune system that may compromise the function of several organs, such as kidney, heart, joints, brain and skin. Corticosteroids (CCS), synthetic and biologic immunosuppressive agents have demonstrated the capacity to improve the course of autoimmune diseases. However, a significant number of patients do not respond or develop resistance to these therapies over time. P-glycoprotein (P-gp) is a transmembrane protein that pumps several drugs out of the cell, including CCS and immunosuppressants; thus, its over-expression or hyper-function has been proposed as a possible mechanism of drug resistance in patients with autoimmune disorders. Recently, different authors have demonstrated that P-gp inhibitors, such as cyclosporine A (CsA) and its analogue Tacrolimus, are able to reduce P-gp expression and or function in SLE, RA and PsA patients. These observations suggest that P-gp antagonists could be adopted to revert drug resistance and improve disease outcome. The complex inter-relationship among drug resistance, P-gp expression and autoimmunity still remains elusive.
Picchianti-Diamanti, Andrea; Rosado, Maria Manuela; Scarsella, Marco; Lagana, Bruno; D'Amelio, Raffaele
Autoimmune disorders constitute a diverse group of phenotypes with overlapping features and a tendency toward familial aggregation. It is likely that common underlying genes are involved in these disorders. Until very recently, no specific alleles--aside from a few common human leukocyte antigen class II genes--had been identified that clearly associate with multiple different autoimmune diseases. In this study, we describe a unique collection of 265 multiplex families assembled by the Multiple Autoimmune Disease Genetics Consortium (MADGC). At least two of nine "core" autoimmune diseases are present in each of these families. These core diseases include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), multiple sclerosis (MS), autoimmune thyroid disease (Hashimoto thyroiditis or Graves disease), juvenile RA, inflammatory bowel disease (Crohn disease or ulcerative colitis), psoriasis, and primary Sjogren syndrome. We report that a recently described functional single-nucleotide polymorphism (rs2476601, encoding R620W) in the intracellular tyrosine phosphatase (PTPN22) confers risk of four separate autoimmune phenotypes in these families: T1D, RA, SLE, and Hashimoto thyroiditis. MS did not show association with the PTPN22 risk allele. These findings suggest a common underlying etiologic pathway for some, but not all, autoimmune disorders, and they suggest that MS may have a pathogenesis that is distinct from RA, SLE, and T1D. DNA and clinical data for the MADGC families are available to the scientific community; these data will provide a valuable resource for the dissection of the complex genetic factors that underlie the various autoimmune phenotypes. PMID:15719322
Criswell, Lindsey A; Pfeiffer, Kirsten A; Lum, Raymond F; Gonzales, Bonnie; Novitzke, Jill; Kern, Marlena; Moser, Kathy L; Begovich, Ann B; Carlton, Victoria E H; Li, Wentian; Lee, Annette T; Ortmann, Ward; Behrens, Timothy W; Gregersen, Peter K
Autoimmunity to thyroid antigens leads to two distinct pathogenic processes with opposing clinical outcomes: hypothyroidism in Hashimoto's thyroiditis and hyperthyroidism in Graves' disease. The high frequency of these diseases and easy accessibility of the thyroid gland has allowed the identification of key pathogenic mechanisms in organ-specific autoimmune diseases. In early investigations, antibody- and T-cell-mediated death mechanisms were proposed as being
Giorgio Stassi; Ruggero De Maria
Grover's disease (GD) is a transient or persistent, monomorphous, papulovesicular, asymptomatic or pruritic eruption classified as non-familial acantholytic disorder. Contribution of autoimmune mechanisms to GD pathogenesis remains controversial. The purpose of this study was to investigate antibody-mediated autoimmunity in 11 patients with GD, 4 of which were positive for IgA and/or IgG antikeratinocyte antibodies by indirect immunofluorescence. We used the most sensitive proteomic technique for an unbiased analysis of IgA- and IgG-autoantibody reactivities. Multiplex analysis of autoantibody responses revealed autoreactivity of all 11 GD patients with cellular proteins involved in the signal transduction events regulating cell development, activation, growth, death, adhesion and motility. Semiquantitative fluorescence analysis of cultured keratinocytes pretreated with sera from each patient demonstrated decreased intensity of staining for desmoglein 1 and/or 3 and PCNA, whereas 4 of 10 GD sera induced BAD expression, indicating that binding of autoantibodies to keratinocytes alters expression/function of their adhesion molecules and activates apoptosis. We also tested the ability of GD sera to induce visible alterations of keratinocyte shape and motility in vitro but found no specific changes. Thus, our results demonstrated that humoral autoimmunity in GD can be mediated by both IgA and IgG autoantibodies. At this point, however, it is impossible to conclude whether these autoantibodies cause or are caused by the disease. Antidesmoglein antibodies may be triggered by exposure to immune system of sequestered antigens due to disintegration of desmosomes during primary acantholysis. Clarifying aetiology of GD will help improve treatment, which currently is symptomatic and of marginal effectiveness. PMID:24131368
Phillips, Courtney; Kalantari-Dehaghi, Mina; Marchenko, Steve; Chernyavsky, Alex I; Galitovskiy, Valentin; Gindi, Vivian; Chun, Sookhee; Paslin, David; Grando, Sergei A
Methods A total of 176 families (386 individuals and 1107 fi rst-degree relatives) were characterised for a history of other autoimmune disorders. Family-based or case-control analyses were done to assess the association of cytotoxic T-lymphocyte-antigen 4 (CTLA4) and protein tyrosine phosphatase (PTPN22) variants with susceptibility to multiple sclerosis. Findings 46 (26%) index cases reported at least one coexisting autoimmune disorder.
Lisa F Barcellos; Brinda B Kamdar; Patricia P Ramsay; Cari DeLoa; Robin R Lincoln; Stacy Caillier; Silke Schmidt; Jonathan L Haines; Margaret A Pericak-Vance; Jorge R Oksenberg; Stephen L Hauser
Liver transplantation (LT) is a standard therapeutic approach for the treatment of end-stage acute and chronic liver disease\\u000a of various etiologies including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis\\u000a (PSC). Results of LT for these autoimmune liver diseases are good, with a patient survival of 80 to 85% at 5 yr after LT.\\u000a Transplant recipients, however,
Hiromi Ishibashi; Shinji Shimoda; Minoru Nakamura; M. Eric Gershwin
Autoimmune diseases are among the leading causes of death among young and middle-aged women in the United States. Incidence rates vary among the autoimmune diseases, with estimates ranging from less than one newly-diagnosed case of systemic sclerosis to more than 20 cases of adult-onset rheumatoid arthritis per 100000 person-years. Prevalence rates range from less than 5 per 100000 (e.g. chronic
Glinda S Cooper; Berrit C Stroehla
Autoimmune diseases appear to have multiple contributing factors including genetics, epigenetics, environmental factors, and\\u000a aging. The predominance of females among patients with autoimmune diseases suggests possible involvement of the X chromosome\\u000a and X chromosome inactivation. X chromosome inactivation is an epigenetic event resulting in multiple levels of control for\\u000a modulation of the expression of X-linked genes in normal female cells
Wesley H. Brooks
Cases of acute hepatitis induced by statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been reported. A 65-year-old woman was admitted to our hospital because of fatigue, jaundice and altered liver function tests while on treatment with atorvastatin. On the basis of clinical, serological and histological findings, a score leading to a diagnosis of autoimmune hepatitis was reached. We suggest that atorvastatin may have revealed an underlying autoimmune hepatitis. PMID:12867804
Pelli, Nicoletta; Setti, Maurizio; Ceppa, Paola; Toncini, Carlo; Indiveri, Francesco
anti-CD3, antigen-specific treatment, autoimmune diabetes, cellular therapy, combination therapy, immune intervention, regulatory T cell, systemic immune modulation, Type 1 diabetes mellitus Type 1 diabetes results from autoimmune destruction of insulin-producing ? cells in the pancreatic islets, leading to deficiency in glucose uptake by the cells of the body. The resulting complications and mortality call into attention the need for therapeutic
Christophe M Filippi; Matthias G von Herrath
The role of NK cells in autoimmunity has not been extensively studied. Speaking for a disease-promoting role for NK cells\\u000a in autoimmune diseases are recent results suggesting that IFN-? production by NK cells may help adaptive immune responses\\u000a diverge in the direction of a Th1 response. NK cells may also be involved in direct killing of tissue cells, which could
S. Johansson; H. Hall; L. Berg; P. Höglund
Hematopoietic stem cells (HSCs) are the earliest cells of the immune system, giving rise to B and T lymphocytes, monocytes,\\u000a tissue macrophages, and dendritic cells. In animal models, adoptive transfer of HSCs, depending on circumstances, may cause,\\u000a prevent, or cure autoimmune diseases. Clinical trials have reported early remission of otherwise refractory autoimmune disorders\\u000a after either autologous or allogeneic hematopoietic stem
Richard K. Burt; Shimon Slavin; William H. Burns; Alberto M. Marmont
Thyroid autoimmune disorders comprise more than 30% of all organ-specific autoimmune diseases and are characterized by autoantibodies and infiltrating T cells. The pathologic role of infiltrating T cells is not well defined. To address this issue, we generated transgenic mice expressing a human T-cell receptor derived from the thyroid-infiltrating T cell of a patient with thyroiditis and specific for a
Ester Badami; Yun Yun Pang; Istvan Bartok; Julian Dyson; Dimitris Kioussis; Marco Londei; Luigi Maiuri; Sonia Quaratino
Increasing awareness of the importance of aberrant B cell regulation in autoimmunity has driven the clinical development of\\u000a novel B cell-directed biologic therapies with the potential to treat a range of autoimmune disorders. The first of these drugs—rituximab,\\u000a a chimeric monoclonal antibody against the B cell-specific surface marker CD20—was recently approved for treating rheumatoid\\u000a arthritis in patients with an inadequate
D. G. Arkfeld
Vitiligo is a common skin and hair depigmentary disorder that results from selective destruction of melanocytes. It occurs\\u000a in a typical multifactorial, polygenic inheritance. Several studies have indicated that vitiligo is associated with some autoimmune\\u000a diseases. In this paper we examined 6,516 vitiligo patients including clinical characteristics, familial involvement, and\\u000a their association with other autoimmune diseases. Compared with sporadic vitiligo
Zheng Zhang; Sheng-Xin Xu; Feng-Yu Zhang; Xian-Yong Yin; Sen Yang; Feng-Li Xiao; Wen-Hui Du; Jian-Feng Wang; Yong-Mei Lv; Hua-Yang Tang; Xue-Jun Zhang
BackgroundAutoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD), an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD) in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL).Methods and FindingsWe estimated the prevalence of AD in
Irene Gazquez; Andres Soto-Varela; Ismael Aran; Sofia Santos; Angel Batuecas; Gabriel Trinidad; Herminio Perez-Garrigues; Carlos Gonzalez-Oller; Lourdes Acosta; Jose A. Lopez-Escamez
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; also called APS-1,) is a rare autosomal recessive\\u000a disorder that is more frequent in certain isolated populations. It is characterized by two of the three major clinical symptoms\\u000a that may be present: Addison’s disease, and\\/or hypoparathyroidism and\\/or chronic mucocutaneous candidiasis. We have recently\\u000a identified the gene for APECED, which we termed AIRE (for autoimmune regulator). AIRE
M. C. Rosatelli; Alessandra Meloni; Antonella Meloni; Marcella Devoto; Antonio Cao; H. S. Scott; Pärt Peterson; Maarit Heino; Kai J. E. Krohn; Kentaro Nagamine; J. Kudoh; Nobuyoshi Shimizu; Stylianos E. Antonarakis
We report a patient with a seronegative autoimmune panencephalitis, adding a subtype to the emerging spectrum of seronegative autoimmune encephalitis, and we review the sparse literature on isolated psychiatric presentations of autoimmune encephalitis. (A PubMed search for "seronegative autoimmune encephalitis," "nonvasculitic autoimmune inflammatory meningoencephalitis," and related terms revealed <25 cases.) A 15-year-old girl developed an acute-onset isolated psychosis with prominent negative symptoms and intermittent encephalopathy. Despite clinical worsening, her brain magnetic resonance imaging (MRI) scans remained normal for 7 years. Serology was negative for voltage-gated potassium channel (VGKC)-complex, N-methyl-D-aspartate receptor (NMDAR), and glutamic acid decarboxylase (GAD) autoantibodies. We excluded genetic, metabolic, paraneoplastic, degenerative, and infectious etiologies. The patient's symptoms remitted fully with immune therapy, but recurred in association with widespread bihemispheric brain lesions. Brain biopsy revealed mild nonvasculitic inflammation and prominent vascular hyalinization. Immune therapy with plasma exchanges cleared the MRI abnormalities but, 10 years after onset, the patient still suffers neuropsychiatric sequelae. We conclude that autoimmune panencephalitis seronegative for VGKC-complex, NMDAR, and GAD autoantibodies is a subtype of autoimmune encephalitis that can present with pure neuropsychiatric features and a normal brain MRI. Immunologic mechanisms may account for psychiatric symptoms in a subset of patients now diagnosed with classical psychotic disorders. Delay in starting immune therapy can lead to permanent neuropsychiatric sequelae. We propose a standardized classification system for the autoimmune encephalitides, integrating earlier pathology-oriented terms with more recently defined serologic and clinical phenotypes. PMID:23538571
Najjar, Souhel; Pearlman, Daniel; Devinsky, Orrin; Najjar, Amanda; Nadkarni, Siddhartha; Butler, Tracy; Zagzag, David
... and their FAMILIES EMOTIONAL DISORDERS IN PEOPLE WITH MULTIPLE SCLEROSIS This fact sheet presents the current research on ... manage their MS • Lead to suicide What is MS? MS is thought to be an autoimmune disease ...
Some adjuvants may exert adverse effects upon injection or, on the other hand, may not trigger a full immunological reaction. The mechanisms underlying adjuvant adverse effects are under renewed scrutiny because of the enormous implications for vaccine development. In the search for new and safer adjuvants, several new adjuvants were developed by pharmaceutical companies utilizing new immunological and chemical innovations. The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of special immune receptors called toll-like receptors (TLRs) that are expressed on leukocyte membranes. The very fact that TLR activation leads to adaptive immune responses to foreign entities explains why so many adjuvants used today in vaccinations are developed to mimic TLR ligands. Alongside their supportive role, adjuvants were found to inflict by themselves an illness of autoimmune nature, defined as 'the adjuvant diseases'. The debatable question of silicone as an adjuvant and connective tissue diseases, as well as the Gulf War syndrome and macrophagic myofaciitis which followed multiple injections of aluminium-based vaccines, are presented here. Owing to the adverse effects exerted by adjuvants, there is no doubt that safer adjuvants need to be developed and incorporated into future vaccines. Other needs in light of new vaccine technologies are adjuvants suitable for use with mucosally delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. In particular, there is demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. More adjuvants were approved to date besides alum for human vaccines, including MF59 in some viral vaccines, MPL, AS04, AS01B and AS02A against viral and parasitic infections, virosomes for HBV, HPV and HAV, and cholera toxin for cholera. Perhaps future adjuvants occupying other putative receptors will be employed to bypass the TLR signaling pathway completely in order to circumvent common side effects of adjuvant-activated TLRs such as local inflammation and the general malaise felt because of the costly whole-body immune response to antigen. PMID:19880572
Israeli, E; Agmon-Levin, N; Blank, M; Shoenfeld, Y
OBJECTIVE. Autoimmune pancreatitis (AIP) is a rare chronic relapsing steroid-responsive fibroinflammatory disorder of the pancreas that is likely caused by immune dysregulation. It is now thought that AIP consists of two distinct clinicopathologic syndromes currently designated as types 1 and 2. CONCLUSION. A current update on etiopathogenesis, pathology, and clinical and imaging findings of AIP is provided with an emphasis on diagnosis and management. PMID:24758653
Khandelwal, Ashish; Shanbhogue, Alampady Krishna; Takahashi, Naoki; Sandrasegaran, Kumaresan; Prasad, Srinivasa R
Introduction Hypothyroidism is associated with pregnancy complications both for the mother and progeny and it should be considered in reproductive\\u000a age. Thyroid autoimmunity is stated to be the main cause of hypothyroidism in iodine sufficient areas. Polycystic ovary syndrome\\u000a (PCOS) is known as the most common endocrine disorder affecting women in reproductive age. Early diagnosis and treatment of\\u000a hypothyroidism in PCOS
Maryam Kachuei; Fatemeh Jafari; Ali Kachuei; Ammar H. Keshteli
Abstract Significance: The signaling function of redox molecules is essential for an efficient and proper execution of a large number of cellular processes, contributing to the maintenance of cell homeostasis. Excessive oxidative stress is considered as playing an important role in the pathogenesis of autoimmune diseases by enhancing inflammation and breaking down the immunological tolerance through protein structural modifications that induce the appearance of neo/cryptic epitopes. Recent Advances: There is a complex reciprocal relationship between oxidative stress and both apoptosis and autophagy, which is essential to determine cell fate. This is especially relevant in the context of autoimmune disorders in which apoptosis and autophagy play a crucial pathogenic role. Critical Issues: In this review, we describe the latest developments with regard to the involvement of redox molecules in the initiation and progression of autoimmune disorders, focusing on their role in cell fate regulation. We also discuss new therapeutic approaches that target oxidative stress in the treatment of these disorders. The administration of antioxidants is scarcely studied in autoimmunity, and future analyses are needed to assess its beneficial effects in preventing or ameliorating these diseases. Future Directions: Deciphering the intricate relationships between oxidative stress and both apoptosis and autophagy in the context of autoimmunity could be critical in elucidating key pathogenic mechanisms and could lead to novel interventions for the clinical management of autoimmune diseases. Antioxid. Redox Signal. 21, 103-122. PMID:24359147
Ortona, Elena; Maselli, Angela; Delunardo, Federica; Colasanti, Tania; Giovannetti, Antonello; Pierdominici, Marina
Autoimmune thyroid diseases (AITD), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are amongst the commonest autoimmune disorders, affecting approximately 5% of the population. Epidemiological data support strong genetic influences on the development of AITD. Since the identification of HLA-DR3 as a major AITD susceptibility gene, there have been significant advances made in our understanding of the genetic mechanisms leading to AITD. We have shown that an amino acid substitution of alanine or glutamine with arginine at position 74 in the HLA-DR peptide-binding pocket is a critical factor in the development of AITD, and we are continuing to dissect these mechanisms at the molecular level. In addition to the MHC class II genes, there are now several other confirmed gene-loci associated with AITD, including immune-regulatory (CD40, CTLA-4, PTPN22, FOXP3, and CD25) and thyroid-specific genes (thyroglobulin and TSHR). Mechanistically, it is postulated that susceptibility genes interact with certain environmental triggers to induce AITD through epigenetic effects. In this review, we summarize some of the recent advances made in our lab dissecting the genetic-epigenetic interactions underlying AITD. As shown in our recent studies, epigenetic modifications offer an attractive mechanistic possibility which can provide further insight into the etiology of AITD.
Hasham, Alia; Tomer, Yaron
Autoimmune thyroid diseases (AITD), including Graves' disease and Hashimoto's thyroiditis, are among the commonest autoimmune disorders, affecting approximately 5 % of the population. Epidemiological data support strong genetic influences on the development of AITD. Since the identification of HLA-DR3 as a major AITD susceptibility gene, there have been significant advances made in our understanding of the genetic mechanisms leading to AITD. We have shown that an amino acid substitution of alanine or glutamine with arginine at position 74 in the HLA-DR peptide binding pocket is a critical factor in the development of AITD, and we are continuing to dissect these mechanisms at the molecular level. In addition to the MHC class II genes, there are now several other confirmed gene loci associated with AITD, including immune-regulatory (CD40, CTLA-4, PTPN22, FOXP3, and CD25) and thyroid-specific genes (thyroglobulin and TSHR). Mechanistically, it is postulated that susceptibility genes interact with certain environmental triggers to induce AITD through epigenetic effects. In this review, we summarize some of the recent advances made in our laboratory dissecting the genetic-epigenetic interactions underlying AITD. As shown in our recent studies, epigenetic modifications offer an attractive mechanistic possibility that can provide further insight into the etiology of AITD. PMID:22457094
Hasham, Alia; Tomer, Yaron
Sleep disturbance in patients with multiple sclerosis is prevalent and has multifactorial causes. In mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, we determined the dynamic changes of sleep architecture and the interactions between sleep changes and EAE symptoms. The changes of sleep patterns were mainly reflected by altered sleep stage distribution and increased sleep fragmentation. Increased waking and decreased non-rapid eye movement sleep occurred after EAE onset and persisted through the symptomatic phase. There also was increased sleep state transition, indicating a reduction of sleep cohesiveness. Furthermore, the extent of sleep fragmentation correlated with the severity of disease. This is the first study of sleep characteristics in EAE mice demarcating specific changes related to the autoimmune disorder without confounding factors such as psychosocial impact and treatment effects. The reduction of sleep efficiency and cohesiveness supports the notion that enhancing sleep might facilitate the recovery of mice from EAE, pertinent to the multimodality treatment of multiple sclerosis. PMID:24566387
He, Junyun; Wang, Yuping; Kastin, Abba J; Pan, Weihong
Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren's syndrome (pSS) are complex disorders with a genetic background and the involvement of environmental factors, including viruses. The Epstein-Barr virus (EBV) is a plausible candidate for playing a role in the pathophysiology of these diseases. Both SLE and RA are characterized by high titers of anti-EBV antibodies and impaired T-cell responses to EBV antigens. Compared with normal subjects, elevated EBV load in peripheral blood has been observed in SLE and RA. EBV DNA or RNA has been evidenced in target organs of RA (synovium) or pSS (salivary glands). Finally, molecular mimicry has been demonstrated between EBV proteins and self antigens in these three conditions. In addition, SLE, RA, and pSS are associated with an increased risk of lymphoma with a potential role for EBV. The influence of new and emergent treatments of these autoimmune diseases (biological therapies) on EBV load and the course of latent EBV infection requires further studies. PMID:19028369
Toussirot, Eric; Roudier, Jean
Urticaria is one of the most frequent dermatosis, being its prevalence in general population estimated about 20%. This prospective case-control study was aimed at determining the prevalence of thyroid autoimmune disorders in a cohort of patients with chronic urticaria (CU), all living within an area with mild-to-moderate iodine deficiency. Fifty four consecutive patients affected by CU were recruited and compared to 108 healthy controls. Assessment of the thyroid function included measurement of serum concentrations of TSH, FT3, FT4, anti-thyreoglobulin (anti-TG) and anti-peroxidase (anti-TPO) antibodies. Ultrasound scan of the thyroid gland was performed in all subjects using a 7.5 MHz linear transducer. All subjects were followed up for 6 months. The prevalence of thyroid antibodies was significantly higher in our cohort of patients with CU than in controls (22% vs. 6.5 %). Hashimoto's thyroiditis was also more frequent in patients than controls (18.5% vs. 1.8%). These frequencies do not differ from those previously reported by some other authors and confirm the association between CU and thyroid autoimmunity also in the area of iodine deficiency. However, presence of antibodies or thyroiditis does not seem to influence clinical course of CU. These results suggest that screening for thyroid function may be useful in all the patients with CU.
Tauchmanova, Libuse; Colasanti, Paola; Zuccoli, Alfonso; Colao, Annamaria
This review gives an overview of the rehabilitation of autoimmune diseases. After general remarks on rehabilitation, the effects of acute and chronic exercises on inflammatory markers are summarized. Most of the available literature deals with rheumatoid arthritis (RA) and multiple sclerosis (MS), and therefore, rehabilitation of these diseases is described in more detail. Exercise is the main component in the rehabilitation of patients with RA and aims at increasing physical capacity, muscle strength, aerobic endurance, cardiovascular fitness and functional abilities, and helps to prevent secondary deconditioning due to reduced activity levels. Since MS causes a wide range of symptoms, the rehabilitation of these patients requires a multidisciplinary approach and encompasses physiotherapy, exercise therapy, hippotherapy, cognitive rehabilitation, psychological therapy, strategies to improve fatigue and coping programs. The ultimate goal of rehabilitation is to enable patients with chronic conditions to reach and maintain their optimal physical, sensory, intellectual, psychological and social functional levels, and to attain independence and self-determination as far as possible. PMID:21619946
The role of immunity and inflammation in epilepsy have long been suggested by the anticonvulsant activity of steroids in some infancy and childhood epilepsies. The role of fever and infection in exacerbating seizures due to possible proinflammatory molecules, the increased frequency of seizures in systemic autoimmune diseases like systemic lupus erythematous, and, recently, the detection of autoantibodies in some unexplained epilepsies reinforced the causal place of immunity and inflammation in epilepsies with unknown etiology. In this article, we summarize epilepsies where clinical and biologic data strongly support the pathogenic role of autoantibodies (e.g., limbic encephalitides, N-methyl-d-aspartate [NMDA] encephalitis) and epilepsies where immune-mediated inflammation occurs, but the full pathogenic cascade is either not clear (e.g., Rasmussen's encephalitis) or only strongly hypothesized (idiopathic hemiconvulsion-hemiplegia syndrome [IHHS] and fever-induced refractory epilepsy in school-aged children [FIRES]). We emphasize the electroclinical features that would help to diagnose these conditions, allowing early immunomodulating therapy. Finally, we raise some questions that remain unclear regarding diagnosis, mechanisms, and future therapies. PMID:22946722
Our laboratory investigates systemic autoimmune disease in the context of mouse models of systemic lupus erythematosus (SLE). SLE is associated with high titers of serum autoantibodies of the IgG class that are predominantly directed against nuclear antigens, with pathological manifestations that are considered by many to be characteristic of an immune-complex mediated disease. In this review, we focus on the known and potential roles of somatic mutagenesis in SLE. We will argue that anti-nuclear antibodies (ANA) arise predominantly from nonautoreactive B cells that are transformed into autoreactive cells by the process of somatic hypermutation (SHM), which is normally associated with affinity maturation during the germinal center reaction. We will also discuss the role of SHM in creating antigenic peptides in the V region of the B cell receptor (BCR) and its potential to open an avenue of unregulated T cell help to autoreactive B cells. Finally, we will end this review with new experimental evidence suggesting that spontaneous somatic mutagenesis of genes that regulate B cell survival and activation is a rate-limiting causative factor in the development of ANA. PMID:23249093
Detanico, Thiago; St Clair, James B; Aviszus, Katja; Kirchenbaum, Greg; Guo, Wenzhong; Wysocki, Lawrence J
Sexual dimorphism in human immune systems is most apparent in the female predominance of certain autoimmune diseases (ADs) like systemic lupus erythematosus (SLE). Epidemiologic, observational and experimental evidence strongly suggest sex steroids are important modulators of genetic risk in human AD. In this regard, the roles of progesterone (Pg), an immunomodulatory female sex steroid, are poorly understood. Several lines of investigation indicate Pg and synthetic progestins impact risk of AD and immune-mediated injury in different ways depending on their concentrations and their engagement of various Pg receptors expressed in immune organs, immune cells or tissues targeted by immune attack. At low physiologic levels, Pg may enhance interferon-alpha (IFN-?) pathways important in SLE pathogenesis. Commonly used synthetic progestins may have the opposite effect. At pregnancy levels, Pg may suppress disease activity in rheumatoid arthritis (RA) and multiple sclerosis (MS) via inhibition of T helper type 1 (Th1) and Th17 pathways and induction of anti-inflammatory molecules. Importantly, Pg’s immunomodulatory effects differ from those of estrogens and androgens. An additional layer of complexity arises from apparent interdependence of sex hormone signaling pathways. Identifying mechanisms by which Pg and other sex steroids modulate risk of AD and immune-mediated injury will require clarification of their cellular and molecular targets in vivo. These future studies should be informed by recent genetic discoveries in human AD, particularly those revealing their sex-specific genetic associations.
Hughes, Grant C.
Almost 25 years ago, the concept of the 'mosaic of autoimmunity' was introduced to the scientific community, and since then this concept has continuously evolved, with new pebbles being added regularly. We are now looking at an era in which the players of autoimmunity have changed names and roles. In this issue of BMC Medicine, several aspects of autoimmunity have been addressed, suggesting that we are now at the forefront of autoimmunity science. Within the environmental factors generating autoimmunity are now included unsuspected molecules such as vitamin D and aluminum. Some adjuvants such as aluminum are recognized as causal factors in the development of the autoimmune response. An entirely new syndrome, the autoimmune/inflammatory syndrome induced by adjuvants (ASIA), has been recently described. This is the new wind blowing within the branches of autoimmunity, adding knowledge to physicians for helping patients with autoimmune disease. PMID:23557479
Perricone, Carlo; Agmon-Levin, Nancy; Shoenfeld, Yehuda
Almost 25 years ago, the concept of the ‘mosaic of autoimmunity’ was introduced to the scientific community, and since then this concept has continuously evolved, with new pebbles being added regularly. We are now looking at an era in which the players of autoimmunity have changed names and roles. In this issue of BMC Medicine, several aspects of autoimmunity have been addressed, suggesting that we are now at the forefront of autoimmunity science. Within the environmental factors generating autoimmunity are now included unsuspected molecules such as vitamin D and aluminum. Some adjuvants such as aluminum are recognized as causal factors in the development of the autoimmune response. An entirely new syndrome, the autoimmune/inflammatory syndrome induced by adjuvants (ASIA), has been recently described. This is the new wind blowing within the branches of autoimmunity, adding knowledge to physicians for helping patients with autoimmune disease.
The multiple autoimmune syndromes (MAS) consist on the presence of three or more well-defined autoimmune diseases (ADs) in a single patient. The aim of this study was to analyze the clinical and genetic characteristics of a large series of patients with MAS. A cluster analysis and familial aggregation analysis of ADs was performed in 84 patients. A genome-wide microsatellite screen was performed in MAS families, and associated loci were investigated through the pedigree disequilibrium test. Systemic lupus erythematosus (SLE), autoimmune thyroid disease (AITD), and Sjögren's syndrome together were the most frequent ADs encountered. Three main clusters were established. Aggregation for type 1 diabetes, AITD, SLE, and all ADs as a trait was found. Eight loci associated with MAS were observed harboring autoimmunity genes. The MAS represent the best example of polyautoimmunity as well as the effect of a single genotype on diverse phenotypes. Its study provides important clues to elucidate the common mechanisms of ADs (i.e., autoimmune tautology). PMID:22648455
Anaya, Juan-Manuel; Castiblanco, John; Rojas-Villarraga, Adriana; Pineda-Tamayo, Ricardo; Levy, Roger A; Gómez-Puerta, José; Dias, Carlos; Mantilla, Ruben D; Gallo, Juan Esteban; Cervera, Ricard; Shoenfeld, Yehuda; Arcos-Burgos, Mauricio
Th17 and IL-17 play important roles in the clearance of extracellular bacterial and fungal infections. However, strong evidence also implicates the Th17 lineage in several autoimmune disorders including multiple sclerosis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. The Th17 subset has also been connected with type I diabetes, although whether it plays a role in the pathogenicity of or protection from the disease remains a controversial issue. In this review we have provided a comprehensive overview of Th17 pathogenicity and function, including novel evidence for a protective role of Th17 cells in conjunction with the microbiota gut flora in T1D onset and progression.
Bedoya, Simone Kennedy; Lam, Brandon; Lau, Kenneth; Larkin, Joseph
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.
Lestre, Sara; Lozano, Eva; Meireles, Claudia; Barata Feio, Ana
Background The significance of hypergammaglobulinemia as a marker of immune activation is unknown, as a differential diagnosis for hypergammaglobulinemia in children has not been adequately established. The goal of this study was to identify conditions associated with hypergammaglobulinemia in children, with the hypothesis that elevated immunoglobulin levels may precede or predict the development of autoimmune conditions. Methods We reviewed the medical records for all children with IgG level ?2000 mg/dL treated at a tertiary care children’s hospital from January 1, 2000 through December 31, 2009. We compared clinical and laboratory features of these patients, and developed an algorithm to predict the likelihood of underlying autoimmunity based on these characteristics. Results After excluding children who had received IVIG, a total of 442 patients with hypergammaglobulinemia were identified. Of these, nearly half had autoimmune conditions, most frequently systemic lupus erythematosus and lupus-related disorders. Autoimmune gastrointestinal disorders such as inflammatory bowel disease were also common. Infectious diseases were the next largest category of diseases, followed with much less frequency by malignant, drug-related, and other conditions. In comparison with non-autoimmune conditions, patients with autoimmune disease had higher IgG levels, lower white blood cell counts, lower hemoglobin values, and lower C-reactive protein (CRP) levels. Multivariable logistic regression confirmed that CRP (P?=?0.002), white blood cell count (P?0.001), hemoglobin (P?=?0.015), and female gender (P?0.001) are independent risk factors for autoimmune disease in patients with high IgG levels. Conclusions In a cohort of pediatric patients at a tertiary care children’s hospital, hypergammaglobulinemia was most commonly associated with autoimmune diseases. In female patients with hypergammaglobulinemia, the presence of leukopenia, anemia, and normal CRP was 95% predictive of underlying autoimmune disease.
We report on a 19-year-old woman with polyglandular autoimmune syndrome type II (APS II). She was diagnosed with addison's disease and hypothyroidism due to chronic autoimmune thyroiditis. Her mother had celiac disease and her brohter had diabetes mellitus typ 1. Chronic autoimmune thyroiditis was diagnosed in her mother, subsequently. In patients and their relatives, who have autoimmune disorders, a search for autoimmune polyglandular syndrome is crucial. Consequently, it would be appropriate that the patient and all family members are asked for clinical signs and symptoms of autoimmune disorders. Annual measurement of morning cortisol, TSH and fasting plasma glucose may useful. Screening of affected individuals as well as their first-degree relatives for celiac disease is recommended. Therapy of APS II consists of hormone replacement therapy, but thyroxin replacement may induce life-threatening adrenal failure in a patient with untreated Addison's disease. Thus, in case of doubt hydrocortisone should be given before the thyroxine administration is started. PMID:18303665
Lipowsky, C; Schorl-Schweikardt, B A; Kehl, Oth; Brändle, M
Autoimmune thyroiditis, of which Hashimoto thyroiditis represents the most frequent form, is an inflammatory state of the thyroid gland that results from the interaction between genetic variants that promote susceptibility and environmental factors. High iodine intake, selenium deficiency, pollutants such as tobacco smoke, infectious diseases such as chronic hepatitis C, and certain drugs are implicated in the development of autoimmune thyroiditis, primarily in genetically predisposed people. Long-term iodine exposure leads to increased iodination of thyroglobulin, which increases its antigenicity and initiates the autoimmune process in genetically susceptible individuals. Selenium deficiency decreases the activity of selenoproteins, including glutathione peroxidases, which can lead to raised concentrations of hydrogen peroxide and thus promote inflammation and disease. Such environmental pollutants as smoke, polychlorinated biphenyls, solvents and metals have been implicated in the autoimmune process and inflammation. Environmental factors have not yet, however, been sufficiently investigated to clarify their roles in pathogenesis, and there is a need to assess their effects on development of the autoimmune process and the mechanisms of their interactions with susceptibility genes. PMID:18607401
Duntas, Leonidas H
Systemic autoimmunity is a complex disease process that results from a loss of immunological tolerance characterized by the inability of the immune system to discriminate self from non-self. In patients with the prototypic autoimmune disease systemic lupus erythematosus (SLE), formation of autoantibodies targeting ubiquitous nuclear antigens and subsequent deposition of immune complexes in the vascular bed induces inflammatory tissue injury that can affect virtually any organ system. Given the extraordinary genetic and phenotypic heterogeneity of SLE, one approach to the genetic dissection of complex SLE is to study monogenic diseases, for which a single gene defect is responsible. Considerable success has been achieved from the analysis of the rare monogenic disorder Aicardi-Goutičres syndrome (AGS), an inflammatory encephalopathy that clinically resembles in-utero-acquired viral infection and that also shares features with SLE. Progress in understanding the cellular and molecular functions of the AGS causing genes has revealed novel pathways of the metabolism of intracellular nucleic acids, the major targets of the autoimmune attack in patients with SLE. Induction of autoimmunity initiated by immune recognition of endogenous nucleic acids originating from processes such as DNA replication/repair or endogenous retro-elements represents novel paradigms of SLE pathogenesis. These findings illustrate how investigating rare monogenic diseases can also fuel discoveries that advance our understanding of complex disease. This will not only aid the development of improved tools for SLE diagnosis and disease classification, but also the development of novel targeted therapeutic approaches. PMID:23786362
Lee-Kirsch, M A; Wolf, C; Günther, C
Background: To evaluate the involvement of immune abnormality in patients with idiopathic premature ovarian insufficiency (POI). In addition to the known etiology, autoimmune disorders may be a pathologic mechanism for POI. Materials and Methods: Our study was a prospective controlled trial. Twenty women with POI, reasons other than autoimmune excluded, were enrolled in this study. The control group consisted of 17 healthy women. In both groups, family and personal history were taken and the levels of follicle stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, prolactin, anti-Müllerian hormone, inhibin B, antithyroglobulin and antithyroid peroxidase antibodies were determined. Antiovarian antibodies and subpopulations of peripheral blood T-lymhocytes were also determined. Results: Participants in the study group exhibited hypergonadotropichypogonadism, while high levels of follicle stimulating hormone and low levels of inhibin B and anti-Müllerian hormone were observed. In 16 (80%) patients, POI was associated in their personal and familial history with another autoimmune disease. Fifty percent of patients presented highly elevated antithyroid antibodies. The lymphocyte subset, especially B cells, was significantly higher (p=0.014), and peripheral regulatory lymphocytes CD25+ high were significantly lower (p=0.015) in the study group than in the control group. Anti- ovarian antibodies were detected in 20% of patients with POI. Conclusion: We presume that the presence of anti-ovarian antibodies together with abnormalities of cellular immunity may in some cases potentially represent the involvement of an autoimmune mechanism in idiopathic POI.
Kosir Pogacnik, Renata; Meden Vrtovec, Helena; Vizjak, Alenka; Ursula Levicnik, Alenka; Slabe, Nina; Ihan, Alojz
Sarcoidosis (SA) is a granulomatous disorder of an unknown etiology. Infectious, genetic factors and autoimmunity have been explored as potential causes of SA. Pathologic similarities between SA and tuberculosis (TB) suggest Mycobacterium tuberculosis, especially mycobacterial antigen(s) e.g. heat shock proteins (Mtb-hsp) as causative factors. Mtb-hsp, especially Mtb-hsp65, may provide a link between infection and autoimmunity by cross-reactivity between the mycobacterial and human hsp. There is 100% homology between M.tuberculosis and Mycobacterium bovis BCG hsp. In light of evidences necessary to establish SA which is autoimmune in origin, my recently published findings prompted me to raise the hypothesis that, in genetically different individuals, the same antigens (Mtb-hsp) may induce different immune responses, leading to the development of SA or TB. The hypothesis seems to have been supported by an epidemiological analysis of the worldwide SA and TB prevalences that reveal that the TB distribution is approximately opposite to that of SA. Because one third of the Earth's population has been infected with M.tuberculosis, it is possible that the presence of mycobacterial infection or BCG vaccination (e.g., Mtb-hsp65) in genetically predisposed host may be involved in the development of autoimmunity. PMID:19931650
Data on B cell depletion therapy in severe autoimmune diseases in paediatric patients are very limited. We conducted a retrospective cohort study and recruited patients who were treated with rituximab (RTX) and followed up for at least 6 months through the German societies of paediatric rheumatology and nephrology. The aim was to describe the spectrum of autoimmune disorders for which RTX was used and to describe the applied therapeutic regimens, the observed efficacy, as well as potential immunological side effects. The need to develop standard treatment guidelines for future trials should be discussed. Sixty-five patients were included. Nineteen patients suffered from systemic lupus erythematosus, 13 from vasculitic disorders, 12 from hematological autoimmune diseases, 5 from mixed connective tissue disorders, 4 from juvenile idiopathic arthritis, and 9 had other autoimmune diseases. Adverse, infusion-related events were reported in 12/65 (18%) patients. Considering laboratory and clinical parameters, 13 patients (22%) were in complete remission, 31 (52%) were in partial remission, 6 (10%) were unchanged and 10 (17%) had progressed after 6 months. In 46% of the patients, the steroid dose could be more than halved. IgG, IgM and IgA decreased from normal levels prior to RTX therapy to below normal levels at 6 months in 2/22 (9%), 10/21 (48%), and 4/22 (18%) patients, respectively. Immunoglobulin deficiency or prolonged CD20 depletion was reported in eight patients after an observation period longer than 12 months. RTX therapy led to a perceivable reduction in disease activity. However, long-term immunological alterations may occur in more than 10% of the patients. Guidelines and protocols for off-label therapy are desirable to document reasonable follow-up data. Controlled prospective studies for RTX therapies in children with standardised therapeutic and diagnostic protocols are urgently needed. PMID:21120559
Jansson, Annette F; Sengler, Claudia; Kuemmerle-Deschner, Jasmin; Gruhn, Bernd; Kranz, A Birgitta; Lehmann, Hartwig; Kleinert, Daniela; Pape, Lars; Girschick, Hermann J; Foeldvari, Ivan; Haffner, Dieter; Haas, Johannes P; Moebius, Dagmar; Foell, Dirk; Peitz, Joachim; Grote, Veit
Once systemic disease is in remission, it is prudent to recognize the importance of alopecia in the patient's overall sense of well-being and quality-of-life clinical outcome. Scarring alopecia (scalp discoid lupus erythematosus) can be the presenting manifestation of lupus in more than half of affected individuals. Diffuse nonscarring alopecia in lupus is usually responsive to treatment of the systemic disease. Severe, often intractable burning pruritus of the scalp is a frequent complaint in dermatomyositis. Lichen planopilaris may mimic other autoimmune forms of scarring alopecia. Alopecia can also be caused by medications used to treat systemic autoimmune disease and fibromyalgia. PMID:23159178
Moghadam-Kia, Siamak; Franks, Andrew G
To explain the pathogenesis of autoimmunity, we hypothesize that following an infection the immune response spreads to tissue-specific autoantigens in genetically predisposed individuals eventually determining progression to disease. Molecular mimicry between viral and self antigens could, in some instances, initiate autoimmunity. Local elicitation of inflammatory cytokines following infection probably plays a pivotal role in determining loss of functional tolerance to self autoantigens and the destructive activation of autoreactive cells. We also describe the potential role of interleukin 10, a powerful B-cell activator, in increasing the efficiency of epitope recognition, that could well be crucial to the progression toward disease.
Gianani, R; Sarvetnick, N
Autoimmune thyroiditis (AIT) is an autoimmune disease with genetic background. Women are more likely to develop AIT. In adulthood, AIT is the most frequent cause for acquired hypothyroidism. Cytotoxic T-lymphocyte antigen (CTL-4) may play a role in the etiology of the disease. Diagnosis is made by determination of elevated antibodies against thyroid peroxidase and thyroglobulin, and a hypoechoic pattern in ultrasound. In case of hypothyroidism a substitutive therapy with levothyroxine is necessary. AIT may occur as postpartum thyroiditis or as a special entity as consequence of therapy with cytokines. PMID:19941232
\\u000a The autoimmune diseases can be divided into two basic categories: organ specific and systemic. Organ specific autoimmune disease can affect virtually any tissue of the body and is associated most often with evidence\\u000a of both T and B cell autoimmune responses directed against the cells of the affected organ. Examples of organ specific autoimmune\\u000a disease include multiple sclerosis, Type I
Timothy M. Wright; Dana P. Ascherman
The incidence of autoimmune diseases has shown a significant increase in developed countries during the last 40 years. The cause of this increase is still unknown, and reliable methods for the detection of individuals at risk of developing autoimmune disease are not available yet. To explore new methods for the diagnosis and monitoring of autoimmune disease, we have studied the repertoire
Francisco J. Quintana; Irun R. Cohen
The involvement of autoimmune mechanisms in premature ovarian failure has been put forward by numerous investigators. In various other ovarian pathologies, such as idiopathic infertility, polycystic ovary syndrome, or endometriosis, similar mechanisms have been suggested. However, the exact role of autoimmunity in the pathophysiology of these diseases still remains controversial. The diagnosis of autoimmune ovarian disease relies on several clinical,
T. Forges; P. Monnier-Barbarino; G. C. Faure; M. C. Bene
The possible consequences of the progressive ‘ageing’ of the immune system are the increase in autoimmune phenomenon, incidence of neoplasia and predisposition to infections. This review analyses the clinical expression of the systemic autoimmune diseases in older patients, focusing on three specific characteristics: the frequent atypical presentation of autoimmune diseases in the elderly, the higher morbidity and mortality of these
Manuel Ramos-Casals; Pilar Brito-Zerón; Alfonso López-Soto
A specific and sensitive assay was performed to detect both anti-SS-A/Ro and anti-SS-B/La antibodies in sera of patients with autoimmune diseases, including systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), Sjögren's syndrome (SS), discoid lupus erythematosus (DLE), mixed connective tissue disease (MCTD), generalized morphea (GM), and dermatomyositis (DM). The SS-A/Ro and SS-B/La antigens were prepared from human spleen (HSE) and cultured human cell line (KB cells, KBE), white rabbit thymus extract (RTE) was used as the SS-B/La antigen marker. The antigens were partially purified by DEAE cellulose column chromatography. Immunoblotting showed that the SS-A/Ro antibody reacts mainly with the 58-kDa peptide of the partially purified antigen. Sera containing both the SS-A/Ro and SS-B/La antibodies reacted with the 40-kDa peptide of RTE, and the 58-kDa, 42-kDa, and 40-kDa peptides of HSE and KBE. We found that some of the SS-A/Ro antisera could further react with the 64-kDa peptide of HSE and KBE. The 58-kDa peptide is rich in its cytoplasmic fraction of KB cells, and the 4-kDa peptide in nucleoplasmic fraction. The KB cell line is a better source of the antigens than human spleen extract. The immunoblotting method clearly showed that the positivity rates of SS-A/Ro and/or SS-B/La autoantibodies were higher in sera from Japanese patients with SLE compared with titers reported for Caucasians but not in sera from healthy volunteers. PMID:2774641
Inagaki, Y; Jinno, Y; Hamasaki, Y; Ueki, H
In contrast to the large number of studies on autoimmunity against the thyroid gland in patients with type 1 diabetes mellitus, little is known about the anti-islet autoimmune status in patients with autoimmune thyroid diseases (AITDs). We therefore studied the anti-islet autoimmune status in patients with AITD and the clinical and genetic characteristics of AITD patients with anti-islet autoimmunity. The
Masanori Moriguchi; Sinsuke Noso; Yumiko Kawabata; Takaaki Yamauchi; Takeshi Harada; Katsumori Komaki; Naru Babaya; Yoshihisa Hiromine; Hiroyuki Ito; Satomi Yamagata; Kaori Murata; Takahiro Higashimoto; Akinobu Yamamoto; Yasuhiro Ohno; Hiroshi Ikegami
Autoimmune manifestations are paradoxical and frequent complications of primary immunodeficiencies, including T and/or B cell defects. Among pure B cell defects, the Activation-induced cytidine Deaminase (AID)-deficiency, characterized by a complete lack of immunoglobulin class switch recombination and somatic hypermutation, is especially complicated by autoimmune disorders. We summarized in this review the different autoimmune and inflammatory manifestations present in twelve patients out of a cohort of 45 patients. Moreover, we also review the impact of AID mutations on B-cell tolerance and discuss hypotheses that may explain why central and peripheral B-cell tolerance was abnormal in the absence of functional AID. Hence, AID plays an essential role in controlling autoreactive B cells in humans and prevents the development of autoimmune syndromes.
Durandy, Anne; Cantaert, Tineke; Kracker, Sven; Meffre, Eric
Autoimmunity is often observed among individuals with primary immune deficiencies; however, the frequency and role of autoimmunity in Schimke immuno-osseous dysplasia (SIOD) has not been fully assessed. SIOD, which is caused by mutations of SMARCAL1, is a rare autosomal recessive disease with its prominent features being skeletal dysplasia, T cell deficiency, and renal failure. We present a child with severe SIOD who developed rituximab resistant Evans syndrome (ES). Consistent with observations in several other immunodeficiency disorders, a review of SIOD patients showed that approximately a fifth of SIOD patients have some features of autoimmune disease. To our best knowledge this case represents the first patient with SIOD and rituximab resistant ES and the first study of autoimmune disease in SIOD.
Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated, autoimmune disorder characterized by central nervous system inflammation and demyelination, features reminiscent of the human disease, multiple sclerosis (MS). Prior work in the EAE model has suggested that encephalitogenic T cells are of the T helper (Th)-1 phenotype. Our group has performed several studies in the EAE model that suggest that a strategy
Michael K. Racke; Anne R. Gocke; Mark Muir; Asim Diab; Paul D. Drew; Amy E. Lovett-Racke
Experimental autoimmune uveitis (EAU) in Lewis rats is a well-established model for human uveitis. During the last years we used this model to demonstrate extraocular induction of uveitis by antigenic mimicry of environmental antigens with retinal autoantigen and investigated the migration and intraocular reactivation of autoreactive green fluorescent protein (GFP)+ T cells. We could also elaborate several differences between EAU
Gerhild Wildner; Maria Diedrichs-Möhring; Stephan R. Thurau
The braking of tolerance or unresponsiveness to self-antigens, involving the activation of autoreactive lymphocytes, is a critical event leading to autoimmune diseases. The precise mechanisms by which this can occur are mostly unknown. Viruses have been implicated in this process, among other etiological factors, such as genetic predisposition and cytokine activity. Several ways have been proposed by which a viral
Matthias G von Herrath; Michael BA Oldstone
There is growing evidence that the commensal bacteria in the gastrointestinal tract (the gut microbiota) influence the development of autoimmunity in rodent models. Since humans have co-evolved with commensals for millennia, it is likely that people, who are genetically predisposed to autoimmunity, harbor gut microbial communities that similarly influence the onset and/or severity of disease. Beyond the current efforts to identify such disease-promoting or -preventing commensals ("pathobionts" or "symbionts"), it will be important to determine what factors modulate them. Dietary changes are known to affect both the composition and function of the gut microbial communities, which in turn can alter the innate and adaptive immune system. In this review, we focus on the relationships between diet, microbiota, and autoimmune diseases. We hypothesize that the beneficial and life-prolonging effects of caloric restriction on a variety of autoimmune models including lupus might partly be mediated by its effects on the gut microbiome and associated virome, the collection of all viruses in the gut. We give recent examples of the immunomodulatory potential of select gut commensals and their products or diet-derived metabolites in murine models of arthritis, multiple sclerosis, and type 1 diabetes. Lastly, we summarize the published phenotypes of germ-free mouse models of lupus and speculate on any role of the diet-sensitive microbiome and virome in systemic lupus and the related antiphospholipid syndrome. PMID:24763536
Vieira, Sm; Pagovich, Oe; Kriegel, Ma
Polyglandular Autoimmune Syndrom type 1 (PAS-1) or Autoimmune PolyEndocrinopathy Candidiasis-Ectodermal-Dystrophy (APECED) is a rare recessive autosomal disease related to Autoimmune Regulator (AIRE) gene mutations. AIRE is mainly implicated in central and peripheric immune tolerance. Diagnosis was classically based on presence of at least two out of three "majors" criterions of Whitaker's triad (candidiasis, autoimmune hypoparathyroidism and adrenal insufficiency). Presence of one criterion was sufficient when a sibling was previously diagnosed. However, some atypic or poorly symptomatic variants do not correspond to these criterions. As a matter of fact, digestive (malabsorption, pernicious anemia, hepatitis), cutaneous (alopecia, vitiligo, enamel dysplasia) or ophtalmological (keratitis) components could prevail. In these cases, diagnosis could be made by molecular genetics. Prognosis is influenced by genetic (AIRE mutations, HLA), hormonal and environmental (infections) factors. Potentially letal components (hepatitis and severe malabsorption) could be treated by immunosuppressors. Candidiasis and other infections should be carefully screened and treated before beginning those therapies, in order to avoid severe systemic infections. PMID:23182677
Proust-Lemoine, Emmanuelle; Saugier-Veber, Pascale; Wémeau, Jean-Louis
Cell therapy, pioneered for the treatment of malignancies in the form of bone marrow transplantation, has subsequently been tested and successfully employed in autoimmune diseases. Autologous haemopoietic stem cell transplantation (HSCT) has become a curative option for conditions with very poor prognosis such as severe forms of scleroderma, multiple sclerosis, and lupus, in which targeted therapies have little or no
Francesco Dazzi; Jacob M van Laar; Andrew Cope; Alan Tyndall
The main autoimmune blistering skin disorders are pemphigus vulgaris (PV) and bullous pemphigoid (BP). They differ in the inflammatory infiltrate, which is more intense in BP. Inflammation is known to activate coagulation in several disorders. Local and systemic activation of coagulation was evaluated in BP and PV. We studied 20 BP patients (10 active and 10 remittent), 23 PV patients (13 active and 10 remittent) and 10 healthy subjects. The coagulation markers prothrombin fragment F1+2 and D-dimer were measured by enzyme-immunoassays in plasma. The presence of tissue factor (TF), the main initiator of blood coagulation, was evaluated immunohistochemically in skin specimens from 10 patients with active PV, 10 patients with active BP and 10 controls. Plasma F1+2 and D-dimer levels were significantly high in active BP (P = 0·001), whereas in active PV the levels were normal. During remission, F1+2 and D-dimer plasma levels were normal in both BP and PV. TF immunoreactivity was found in active BP but neither in active PV nor in normal skin. TF reactivity scores were higher in active BP than in controls or active PV (P = 0·0001). No difference in TF scores was found between active PV and controls. BP is associated with coagulation activation, which is lacking in PV. This suggests that BP but not PV patients have an increased thrombotic risk. The observation that thrombotic complications occur more frequently in BP than in PV further supports this view.
Marzano, A V; Tedeschi, A; Spinelli, D; Fanoni, D; Crosti, C; Cugno, M
Celiac disease, also known as gluten-sensitive enteropathy and nontropical sprue, is a prevalent autoimmune disorder that is triggered by the ingestion of wheat gluten and related proteins of rye and barley in genetically susceptible individuals. The immune response in celiac disease involves the adaptive, as well as the innate, and is characterized by the presence of anti-gluten and anti-transglutaminase 2 antibodies, lymphocytic infiltration in the epithelial membrane and the lamina propria, and expression of multiple cytokines and other signaling proteins. The disease leads to inflammation, villous atrophy, and crypt hyperplasia in the small intestine. In addition to the intestinal symptoms, celiac disease is associated with various extra-intestinal complications, including bone and skin disease, anemia, endocrine disorders, and neurologic deficits. Gluten-free diet is currently the only effective mode of treatment for celiac disease, but better understanding of the mechanism of the disease is likely to add other choices for therapy in the future. PMID:18589004
Briani, Chiara; Samaroo, Diana; Alaedini, Armin
Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious pathogens) are thought to play a major role in the development of autoimmune diseases. In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity.
Ercolini, A M; Miller, S D
Auto-immune hepatitis (AIH) is a chronic progressive hepatitis of unknown aetiology whose clinical presentation ranges from asymptomatic to fulminant hepatic failure. Corticosteroids and azathioprine, which are considered standard therapy for AIH, may, however, be associated with treatment failures and toxicities. Among the alternative medications under investigation, rituximab, used to treat successfully various auto-immune disorders, has fewer side effects. We report herein the case of a 68-year-old woman who developed AIH with worsening clinical, laboratory and histological features despite high-dose prednisone. On rituximab, the patient showed rapid and dramatic clinical improvement, suggesting a therapeutic role for this medication in severe AIH. Indeed, prospective controlled studies are needed to assess and validate this role. PMID:24206745
Al-Busafi, Said A; Michel, René P; Deschenes, Marc
Immunoglobulins (Ig) or antibodies are heavy plasma proteins, with sugar chains added to amino acid residues by N-linked glycosylation and occasionally by O-linked glycosylation. The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation with activation of complement and activation of effector cells. In addition to this plethora of functions, some antibodies express enzymatic activity. Antibodies endowed with enzymatic properties have been described in human autoimmune manifestations for more than a decade in a variety of disorders such as autoimmune thyroiditis, systemic erythematosus (SLE), scleroderma, rheumatoid arthritis (RA), multiple sclerosis (MS) and acquired hemophilia (AH). Antibodies isolated from these conditions were able to specifically hydrolyze thyroglobulin, DNA, RNA, myelin basic protein (MBP), and factor VIII (FVIII) or factor IX (FIX), respectively. The therapeutic relevance of these findings is discussed.
Wootla, Bharath; Lacroix-Desmazes, Sebastien; Warrington, Arthur E.; Bieber, Allan J.; Kaveri, Srini V.; Rodriguez, Moses
The vaccine safety surveillance system effectively detected a very rare adverse event, narcolepsy, in subjects receiving AS03-adjuvanted A(H1N1) pandemic vaccine made using the European inactivation/purification protocol. The reports of increased cases of narcolepsy in non-vaccinated subjects infected with wild A(H1N1) pandemic influenza virus suggest a role for the viral antigen(s) in disease development. However, additional investigations are needed to better understand what factor(s) in wild influenza infection trigger(s) narcolepsy in susceptible hosts. An estimated 31 million doses of European AS03-adjuvanted A(H1N1) pandemic vaccine were used in more than 47 countries. The Canadian AS03-adjuvanted A(H1N1) pandemic vaccine was used with high coverage in Canada where an estimated 12 million doses were administered. As no similar narcolepsy association has been reported to date with the AS03-adjuvanted A(H1N1) pandemic vaccine made using the Canadian inactivation/purification protocol, this suggests that the AS03 adjuvant alone may not be responsible for the narcolepsy association. To date, no narcolepsy association has been reported with the MF59®-adjuvanted A(H1N1) pandemic vaccine. This review article provides a brief background on narcolepsy, outlines the different types of vaccine preparations including the ones for influenza, reviews the accumulated evidence for the safety of adjuvants, and explores the association between autoimmune diseases and natural infections. It concludes by assimilating the historical observations and recent clinical studies to formulate a feasible hypothesis on why vaccine-associated narcolepsy may not be solely linked to the AS03 adjuvant but more likely be linked to how the specific influenza antigen component of the European AS03-adjuvanted pandemic vaccine was prepared. Careful and long-term epidemiological studies of subjects who developed narcolepsy in association with AS03-adjuvanted A(H1N1) pandemic vaccine prepared with the European inactivation/purification protocol are needed. PMID:24559657
Ahmed, S Sohail; Schur, Peter H; MacDonald, Noni E; Steinman, Lawrence
A striking common feature of many autoimmune diseases in humans and experimental animals, despite differences in pathology, is that females are highly susceptible to autoimmune conditions compared to males. In several animal models, estrogens promote, whereas androgens abrogate, B-cell-mediated autoimmune diseases. To understand mechanisms by which estrogens regulate autoimmunity, it is first necessary to decipher estrogen effects on the normal immune system. Estrogen treatment of nonautoimmune mice diminished lymphocyte numbers in both developmental and mature lymphoid organs. Estrogen dysregulated T- and B-cell balance by inducing selective T-cell hypoactivity and B-cell hyperactivity. Even though estrogen did not alter the relative percentages of splenic T-cell subsets, splenic lymphocytes had a reduced proliferative response to T-cell stimulants and were refractory to rescue from activation-induced apoptosis compared to cells from placebo-treated mice. In contrast, estrogen induced B-cell hyperactivity (promoted autoantibodies to double-stranded DNA and phospholipids, increased numbers of plasma cells, and increased autoantibody yield per B cell). Note that treatment of normal mice with estrogen can alter T- and B-cell regulation and overcome B-cell tolerance to result in autoimmunity in normal individuals. Could environmental estrogens promote some human autoimmune disorders? Is there a link between environmental estrogens and autoimmune disorders, especially since these disorders are reported possibly more frequently? These provocative questions warrant investigation. Our findings on immunomodulatory effects may serve as a benchmark to examine whether endocrine-disrupting chemicals will have similar immunologic effects. Images Figure 1 Figure 2
Ahmed, S A; Hissong, B D; Verthelyi, D; Donner, K; Becker, K; Karpuzoglu-Sahin, E
Whether inflammatory bowel diseases (IBD) can be classified as autoimmune disorders is not established. Since circulating acid-labile interferon-alpha (IFN-alpha) is believed to reflect autoimmune reactions, we tested sera from two groups of IBD patients for the presence of circulating IFN. No detectable IFN was found in 51 serum samples of IBD patients. Furthermore, in no serum sample of IBD patients were neutralizing anti-IFN antibodies found. In contrast, acid-labile IFN-alpha was present in sera from 21/52 HIV-infected and from 6/14 systemic lupus erythematosus patients. These observations provide evidence that IBD differs from systemic autoimmune disorders, at least for the presence of circulating IFN.
Capobianchi, M R; Fais, S; Di Paolo, M C; Agostini, D; Paoluzi, P; Pallone, F; Dianzani, F
Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is an autoimmune condition of the eye that sequentially mimics uveitis, retinitis pigmentosa, and proliferative diabetic retinopathy as it progresses to complete blindness. We identified two different missense mutations in the CAPN5 gene in three ADNIV kindreds. CAPN5 encodes calpain-5, a calcium-activated cysteine protease that is expressed in retinal photoreceptor cells. Both mutations cause mislocalization from the cell membrane to the cytosol, and structural modeling reveals that both mutations lie within a calcium-sensitive domain near the active site. CAPN5 is only the second member of the large calpain gene family to cause a human Mendelian disorder, and this is the first report of a specific molecular cause for autoimmune eye disease. Further investigation of these mutations is likely to provide insight into the pathophysiologic mechanisms of common diseases ranging from autoimmune disorders to diabetic retinopathy. PMID:23055945
Mahajan, Vinit B; Skeie, Jessica M; Bassuk, Alexander G; Fingert, John H; Braun, Terry A; Daggett, Heather T; Folk, James C; Sheffield, Val C; Stone, Edwin M
Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is an autoimmune condition of the eye that sequentially mimics uveitis, retinitis pigmentosa, and proliferative diabetic retinopathy as it progresses to complete blindness. We identified two different missense mutations in the CAPN5 gene in three ADNIV kindreds. CAPN5 encodes calpain-5, a calcium-activated cysteine protease that is expressed in retinal photoreceptor cells. Both mutations cause mislocalization from the cell membrane to the cytosol, and structural modeling reveals that both mutations lie within a calcium-sensitive domain near the active site. CAPN5 is only the second member of the large calpain gene family to cause a human Mendelian disorder, and this is the first report of a specific molecular cause for autoimmune eye disease. Further investigation of these mutations is likely to provide insight into the pathophysiologic mechanisms of common diseases ranging from autoimmune disorders to diabetic retinopathy.
Mahajan, Vinit B.; Skeie, Jessica M.; Bassuk, Alexander G.; Fingert, John H.; Braun, Terry A.; Daggett, Heather T.; Folk, James C.; Sheffield, Val C.; Stone, Edwin M.
Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena. PMID:25036569
Yang, Jianying; Chandrasekharappa, Settara C; Vilboux, Thierry; Smith, Ann C M; Peterson, Erik J
Objective: To evaluate the association between celiac disease and specific anxiety and depressive disorders and to identify potential common pathogenetic links, with particular regard to thyroid function and autoimmunity. Methods: Cases included 36 adult celiac patients, 25 females and 11 males, aged 18–64 years. Controls comprised 144 healthy subjects matched by sex and age with no clinical evidence or family
Mauro Giovanni Carta; Maria Carolina Hardoy; Maria Francesca Boi; Stefano Mariotti; Bernardo Carpiniello; Paolo Usai
An increased prevalence of autoimmune diseases in family members of children with autism spectrum disorders (ASD) has been\\u000a previously reported. ASD is also a common problem co-occurring in children with fragile X syndrome (FXS). Why ASD occurs in\\u000a some individuals with FXS, but not all, is largely unknown. Furthermore, in premutation carrier mothers, there is an increased\\u000a risk for autoimmune
Weerasak Chonchaiya; Flora Tassone; Paul Ashwood; David Hessl; Andrea Schneider; Luis Campos; Danh V. Nguyen; Randi J. Hagerman
While the key initiating processes that trigger human autoimmune diseases remain enigmatic, increasing evidences support the concept that microbial stimuli are among major environmental factors eliciting autoimmune diseases in genetically susceptible individuals. Here, we present an overview of evidences obtained through various experimental models of autoimmunity for the role of microbial stimuli in disease development. Disease onset and severity have been compared in numerous models under conventional, specific-pathogen-free and germ-free conditions. The results of these experiments suggest that there is no uniform scheme that could describe the role played by infectious agents in the experimental models of autoimmunity. While some models are dependent, others prove to be completely independent of microbial stimuli. In line with the threshold hypothesis of autoimmune diseases, highly relevant genetic factors or microbial stimuli induce autoimmunity on their own, without requiring further factors. Importantly, recent evidences show that colonization of germ-free animals with certain members of the commensal flora [such as segmented filamentous bacteria (SFB)] may lead to autoimmunity. These data drive attention to the importance of the complex composition of gut flora in maintaining immune homeostasis. The intriguing observation obtained in autoimmune animal models that parasites often confer protection against autoimmune disease development may suggest new therapeutic perspectives of infectious agents in autoimmunity.
Pasztoi, M.; Misjak, P.; Gyorgy, B.; Aradi, B.; Szabo, T. G.; Szanto, B.; Holub, M. Cs.; Nagy, Gy.; Falus, A.
The development of autoimmune disease is based on the interaction of genetic susceptibility and environmental causes. Environmental factors include infectious and non-infectious agents, with some of these factors being implicated in several autoimmune diseases. Vitamin D is now believed to play a role in the development (or prevention) of several autoimmune diseases, based on its immunomodulatory properties. As well, the increasing incidence of autoimmune disease as one moves away from the equator, may be due to the lack of sunlight, which is crucial for the maintenance of normal vitamin D levels. A deficiency in vitamin D levels or vitamin D receptors is commonly indicated in autoimmune diseases, with multiple sclerosis (MS) being one of the best-studied and well-known examples. However, the role of vitamin D in other autoimmune diseases is not well defined, including autoimmune liver diseases such as primary biliary cirrhosis, autoimmune hepatitis, and primary sclerosing cholangitis. This review will examine the role of vitamin D as an immunomodulator, followed by a comparison of vitamin D in MS versus autoimmune liver disease. From this comparison, it will become clear that vitamin D likely plays a role in the development of autoimmune liver disease, but this area requires further investigation. PMID:23845396
Smyk, Daniel S; Orfanidou, Timoklia; Invernizzi, Pietro; Bogdanos, Dimitrios P; Lenzi, Marco
A 34-year-old woman had suffered from systemic lupus erythematosus (SLE) and autoimmune hemolytic anemia (AIHA) in the teen age. She developed progressive ptosis of the eyelids, and difficulty in swallowing and speaking for several years. Endocrinological studies showed primary hypothyroidism. A serum IgG level was elevated (1,973 mg/dl), and antinuclear antibody, thyroid test and microsome test were positive. A muscle biopsy showed massive inflammatory cell infiltrates in the perivascular area in addition to some myopathic change; some variation in fiber size. Immunological staining demonstrated most of these inflammatory cell infiltrates were CD3+ cells and CD4+ cells were counted more than CD8+ cells (CD4/CD8 = 2.3). The diagnoses were confirmed as oculopharyngeal myopathy and Hashimoto's disease. In addition, she had suffered from SLE and AIHA. Therefore we conclude that manifestation of this myopathy may be associated with some autoimmune process. PMID:8334798
Hashizume, M; Okiyama, R; Orimo, S; Arai, M; Hiyamura, E
Autoimmune pancreatitis (AIP) is a rare disease of unknown pathomechanism. AIP belongs to the IgG4-related disease family and responds well to steroids, although the relapse rate can reach up to 20-30%. Differentiation of AIP from the more common pancreatic cancer can be very challenging. About 20% of autoimmune pancreatitis is diagnosed postoperatively during final histological examination. While each of diagnostic investigations provide some additional information towards definitive diagnosis, the question still remains whether it is possible to prevent unnecessary pancreatic resection. We demonstrate the differential diagnostic opportunities when we present our case as well as discuss the literature data of this condition. In conclusion, we think that in case of a focal pancreatic lesion AIP should always be considered. PMID:24566656
Dede, Kristóf; Salamon, Ferenc; Taller, András; Bursics, Attila
Alopecia areata (AA) is an autoimmune disorder of the hair follicle characterized by inflammatory cell infiltrates around actively growing (anagen) hair follicles. Substance P (SP) plays a critical role in the cutaneous neuroimmune network and influences immune cell functions through the neurokinin-1 receptor (NK-1R). To better understand the role of SP as an immunomodulatory neuropeptide in AA, we studied its
Frank Siebenhaar; Andrey A. Sharov; Eva M. J. Peters; Tatyana Y. Sharova; Wolfgang Syska; Andrei N. Mardaryev; Pia Freyschmidt-Paul; John P. Sundberg; Marcus Maurer; Vladimir A. Botchkarev
This study examined the presence of hypersensitivity to dental and environmental metals in patients with clinical disorders complicated with chronic fatigue syndrome. Three groups of patients were examined through medical history, dental examination, and by using a modifi ed test of blast transformation for metals—MELISA®. The three groups consisted of the following: 22 patients with autoimmune thyroiditis with or without
Ivan Sterzl; Jarmila Procházková; Pavlína Hrdá; Jirina Bártová; Petr Matucha; Vera DM Stejskal
Inhibitors associated with CNS myelin are thought to be important in the failure of axons to regenerate after spinal cord injury and in other neurodegenerative disorders. Here we show that targeting the CNS-specific inhibitor of neurite outgrowth Nogo A by active immunization blunts clinical signs, demyelination and axonal damage associated with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis
Tara Karnezis; Wim Mandemakers; Jonathan L McQualter; Binhai Zheng; Peggy P Ho; Kelly A Jordan; Belinda M Murray; Ben Barres; Marc Tessier-Lavigne; Claude C A Bernard
Two haemagglutination tests using preserved turkey erythrocytes are described for the detection of thyroglobulin and microsomal antibodies, respectively. Comparative studies with the more traditional sheep cell techniques show good correlation of titres when testing sera from patients with autoimmune thyroid disorders. PMID:748386
Cayzer, I; Chalmers, S R; Doniach, D; Swana, G
Two haemagglutination tests using preserved turkey erythrocytes are described for the detection of thyroglobulin and microsomal antibodies, respectively. Comparative studies with the more traditional sheep cell techniques show good correlation of titres when testing sera from patients with autoimmune thyroid disorders.
Cayzer, I; Chalmers, S R; Doniach, D; Swana, G
\\u000a Immunological mechanisms which precipitate autoimmune diabetes involve the influence of a genetic footprint on the phenotype\\u000a of the T-cell response to self-antigens, and on development of pathological outcomes in immune responses resulting in T1D.\\u000a For one of the human diabetes antigens, proinsulin, recent findings allow the emergence of a model in which elements of genetically\\u000a biased T-cell development and peptide
Ivana Durinovic-Belló; Gerald T. Nepom
Autoantibodies against red blood cell antigens are considered the diagnostic hallmark of AIHA: Direct antiglobulin test (DAT) completed by cytofluorometry and specific diagnostic monoclonal antibodies (mAbs) allow for a better understanding of autoimmune hemolytic anemia (AIHA) triggers. Once B-cell tolerance checkpoints are bypassed, the patient loses self-tolerance, if the AIHA is not also caused by an possible variety of secondary
Jean-Francois Lambert; Urs E. Nydegger
Dermatomyositis is an autoimmune disease predominantly affecting skin and muscle. Its poorly understood pathogenesis is increasingly being linked to the overproduction of type 1 interferon-inducible gene transcripts and proteins. Mechanisms have been identified by which chronic sustained accumulation of these proteins might occur and thereby injure tissue in dermatomyositis. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:24687932
Greenberg, Steven A
For more than 2,000 years, it was thought that malignant spirits caused diseases. By the end of nineteenth century, these\\u000a beliefs were displaced by more modern concepts of disease, namely, the formulation of the “germ theory,” which asserted that\\u000a bacteria or other microorganisms caused disease. With the emergence of chronic degenerative and of autoimmune diseases in\\u000a the last century, the causative
V. Pordeus; M. Szyper-Kravitz; R. A. Levy; N. M. Vaz; Y. Shoenfeld
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. PMID:24839445
Salahuddin, Ayesha; Saif, Muhammad Wasif
Recent years have witnessed an explosive growth in available biological data pertaining to autoimmunity research. This includes a tremendous quantity of sequence data (biological structures, genetic and physical maps, pathways, etc.) generated by genome and proteome projects plus extensive clinical and epidemiological data. Autoimmunity research stands to greatly benefit from this data so long as appropriate strategies are available to enable full access to and utilization of this data. The quantity and complexity of this biological data necessitates use of advanced bioinformatics strategies for its efficient retrieval, analysis and interpretation. Major progress has been made in development of specialized tools for storage, analysis and modeling of immunological data, and this has led to development of a whole new field know as immunoinformatics. With advances in novel high-throughput immunology technologies immunoinformatics is transforming understanding of how the immune system functions. This paper reviews advances in the field of immunoinformatics pertinent to autoimmunity research including databases, tools in genomics and proteomics, tools for study of B- and T-cell epitopes, integrative approaches, and web servers. PMID:17178560
Petrovsky, Nikolai; Brusic, Vladimir
IMPORTANCE Use of incretin-based hypoglycemic agents is increasing, but safety data remain limited. We treated a woman with marker-negative autoimmune hepatitis associated with the glucagon-like peptide 1 agonist liraglutide. OBSERVATIONS A young woman with type 2 diabetes mellitus and vitiligo presented with a 10-day history of acute hepatitis. Other than starting liraglutide therapy 4 months prior, she reported no changes in medication therapy and no use of supplements. At admission, aspartate aminotransferase level was 991 U/L; alanine aminotransferase level, 1123 U/L; total bilirubin level, 9.5 mg/dL; and international normalized ratio, 1.3. Results of a liver biopsy demonstrated interface hepatitis with prominent eosinophils and rare plasma cells. The patient's liraglutide therapy was withheld at discharge but her symptoms worsened. A second biopsy specimen revealed massive hepatic necrosis. She started oral prednisone therapy for presumed liraglutide-induced marker-negative autoimmune hepatitis. CONCLUSIONS AND RELEVANCE This case represents, to our knowledge, the first report of liraglutide-induced autoimmune hepatitis. Hepatotoxicity may be an incretin analogue class effect with a long latency period. This case raises prescriber awareness about the potential adverse effects of glucagon-like peptide 1 agonists. Postmarketing studies are needed to define the hepatotoxic potential of these agents. PMID:24733687
Kern, Emily; VanWagner, Lisa B; Yang, Guang-Yu; Rinella, Mary E
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.
Saif, Muhammad Wasif
Studies in both humans and in animal models of specific disorders suggest that polymorphisms of multiple genes are involved in conferring either a predisposition to or protection from autoimmune diseases. Genes encoding polymorphic proteins that regulate immune responses or the rates and extent of metabolism of certain chemical structures have been the focus of much of the research regarding genetic susceptibility. We examine the type and strength of evidence concerning genetic factors and disease etiology, drawing examples from a number of autoimmune diseases. Twin studies of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type I diabetes, and multiple sclerosis (MS) indicate that disease concordance in monozygotic twins is 4 or more times higher than in dizygotic twins. Strong familial associations (odds ratio ranging from 5-10) are seen in studies of MS, type I diabetes, Graves disease, discoid lupus, and SLE. Familial association studies have also reported an increased risk of several systemic autoimmune diseases among relatives of patients with a systemic autoimmune disease. This association may reflect a common etiologic pathway with shared genetic or environmental influences among these diseases. Recent genomewide searches in RA, SLE, and MS provide evidence for multiple susceptibility genes involving major histocompatibility complex (MHC) and non-MHC loci; there is also evidence that many autoimmune diseases share a common set of susceptibility genes. The multifactorial nature of the genetic risk factors and the low penetrance of disease underscore the potential influence of environmental factors and gene-environment interactions on the etiology of autoimmune diseases.
Cooper, G S; Miller, F W; Pandey, J P
The expression of self-antigen in the thymus is believed to be responsible for the deletion of autoreactive T lymphocytes, a critical process in the maintenance of unresponsiveness to self. The Autoimmune regulator (Aire) gene, which is defective in the disorder autoimmune polyglandular syndrome type 1, has been shown to promote the thymic expression of self-antigens. A clear link, however, between specific thymic self-antigens and a single autoimmune phenotype in this model has been lacking. We show that autoimmune eye disease in aire-deficient mice develops as a result of loss of thymic expression of a single eye antigen, interphotoreceptor retinoid-binding protein (IRBP). In addition, lack of IRBP expression solely in the thymus, even in the presence of aire expression, is sufficient to trigger spontaneous eye-specific autoimmunity. These results suggest that failure of thymic expression of selective single self-antigens can be sufficient to cause organ-specific autoimmune disease, even in otherwise self-tolerant individuals.
DeVoss, Jason; Hou, Yafei; Johannes, Kellsey; Lu, Wen; Liou, Gregory I.; Rinn, John; Chang, Howard; Caspi, Rachel; Fong, Lawrence; Anderson, Mark S.
Autoimmune thyroid diseases are common polygenic multifactorial disorders with the environment contributing importantly to the emergence of the disease phenotype. Some of the disease manifestations, such as severe thyroid-associated ophthalmopathy, pretibial myxedema and thyroid antigen/antibody immune complex nephritis are unusual to rare. The spectrum of autoimmune thyroid diseases includes: Graves' disease (GD), Hashimoto's thyroiditis (HT), atrophic autoimmune thyroiditis, postpartum thyroiditis, painless thyroiditis unrelated to pregnancy and thyroid-associated ophthalmopathy. This spectrum present contrasts in terms of thyroid function, disease duration and spread to other anatomic location. The genetic basis of autoimmune thyroid disease (AITD) is complex and likely to be due to genes of both large and small effects. In GD the autoimmune process results in the production of thyroid-stimulating antibodies and lead to hyperthyroidism, whereas in HT the end result is destruction of thyroid cells and hypothyroidism. Recent studies in the field of autoimmune thyroid diseases have largely focused on (i) the genes involved in immune response and/or thyroid physiology with could influence susceptibility to disease, (ii) the delineation of B-cell autoepitopes recognized by the main autoantigens, thyroglobulin, thyroperoxidase and TSH receptor, to improve our understanding of how these molecules are seen by the immune system and (iii) the regulatory network controlling the synthesis of thyroid hormones and its dysfunction in AITD. The aim of the present review is to summarize the current knowledge regarding the relation existing between some susceptibility genes, autoantigens and dysfunction of thyroid function during AITD. PMID:19284442
Hadj-Kacem, H; Rebuffat, S; Mnif-Féki, M; Belguith-Maalej, S; Ayadi, H; Péraldi-Roux, S
It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH. PMID:23859515
Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia
ABSTRACT Leptin represents a link between metabolism, nutritional status, and immune responses. Leptin is important for optimal functioning of the immune system. Leptin is a cytokine-like hormone with proinflammatory properties linked to autoimmune diseases. Moreover, there has been increasing evidence that leptin is involved in the pathogenesis of various autoimmune diseases. Leptin has been shown to enhance immune reactions in autoimmune diseases that are commonly associated with inflammatory responses. Both high and low levels of leptin might contribute to autoimmune diseases. Leptin has been explored as a potential target for therapeutic development in treating autoimmune diseases. In this review, we review here the most recent advances on the role of leptin in autoimmunity and in immune-rheumatological diseases.
COJOCARU, Manole; COJOCARU, Inimioara Mihaela; SILOSI, Isabela; ROGOZ, Suzana
(Full text is available at http://www.manu.edu.mk/prilozi). Splenectomy is therapeutic for a large host of conditions. It is a consequence of expanding the list of disorders and liberalizing the indications for splenectomy in many diseases. Red blood cells disorders: autoimmune hemolytic anemia, hereditary spherocytosis, hemoglobinopathies and thalassemia are prone to splenectomy after failure of medical therapy. A variety of thrombocytopenic disorders are improved by splenectomy, and the most common indication for splenectomy is ITP (idiopathic thrombocytopenic purpura). Splenectomy is successful in reversing hypersplenism in a spectrum of disease called myeloproliferative disorders. Relief of symptoms from splenomegaly is also achieved, but it does not affect the inexorable course of the disorder. The role of splenectomy in white blood cells disorders (leukemias and lymphomas) is only palliative and facilitates chemotherapy. Splenectomy in patients with hemathologic disorders imparts a risk of fulminant and life threatening infection "overwhelming postsplenectomy sepsis" that can be obviated by appropriate treatment. Although splenectomy for hemathologic disorders is only therapeutic and not curative, the relief of symptoms and for some disorders facilitation of chemotherapy leads to better quality of life and longer survival. Key words: Splenectomy, laparoscopic splenectomy, hemathologic dsorders, hereditary spherocytosis, idio-pathic thrombocytopenic purpura, ITP, myeloproliferative disorders, lymphoma, overwhelming posts-plenectomy sepsis. PMID:24798604
Jankulovski, N; Antovic, S; Kuzmanovska, B; Mitevski, A
Autoimmune neutropenia, caused by neutrophil-specific autoantibodies is a common phenomenon in autoimmune disorders such as Felty's syndrome and systemic lupus erythematosus. Felty's syndrome is associated with neutropenia and splenomegaly in seropositive rheumatoid arthritis which can be severe and with recurrent bacterial infections. Neutropenia is also common in systemic lupus erythematosus and it is included in the current systemic lupus classification criteria. The pathobiology of the autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus is complex, and it could be a major cause of morbidity and mortality due to increased risk of sepsis. Treatment should be individualized on the basis of patient's clinical situation, and prevention or treatment of the infection. Recombinant human granulocyte colony-stimulating factor is a safe and effective therapeutic modality in management of autoimmune neutropenia associated with Felty's syndrome and systemic lupus erythematosus, which stimulates neutrophil production. There is a slight increased risk of exacerbation of the underlying autoimmune disorder, and recombinant human granulocyte colony-stimulating factor dose and frequency should be adjusted at the lowest effective dose. PMID:21255689
Newman, Kam A; Akhtari, Mojtaba
We report two elderly patients with seronegative Sjögren syndrome who showed benign swelling of the pancreas on computed tomography. Immunostaining of the biopsied lip tissue or serum examination confirmed an increase in production of IgG4, leading to a diagnosis of autoimmune sclerosing pancreatitis (ASP) as a cause of the asymptomatic swelling of the pancreas. Sicca symptoms and ASP spontaneously improved in one patient, and the other responded well to oral prednisolone. Seronegative Sjögren syndrome and ASP can concurrently occur as a clinical manifestation of the IgG4-related systemic disorder, particularly in elderly subjects, and, in such a case, corticosteroid may be a potent therapeutic option. PMID:16362447
Matsuda, Masayuki; Hamano, Hideaki; Yoshida, Takuhiro; Gono, Takahisa; Uehara, Takeshi; Kawa, Shigeyuki; Ikeda, Shu-ichi
\\u000a Source and amount of dietary fat intake modulate cardiovascular disease, malignancy, and autoimmune disorders. Controlled\\u000a clinical studies reveal n-3 fatty acids are able to decrease symptoms and severity of rheumatoid arthritis and systemic lupus erythematosus. Other\\u000a studies reveal a reduction in the need for anti-inflammatory medications along with significant clinical benefits. When comparing\\u000a n-6 lipid-fed animals with n-3 lipid-fed animals,
Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies (Aabs) toward intracellular enzymes are a hallmark for APS1 and serve as diagnostic markers and predictors for disease manifestations. In this study, we aimed to identify pituitary autoantigens in patients with APS1. A pituitary cDNA expression library was screened with APS1 sera and a tudor domain containing protein 6 (TDRD6) cDNA clone was isolated. Positive immunoreactivity against in vitro translated TDRD6 fragments was shown in 42/86 (49%) APS1 patients but not in patients with other autoimmune diseases or in healthy controls. By using immunohistochemistry, sera from 3/6 APS1 patients with growth hormone (GH) deficiency showed immunostaining of a small number of guinea pig anterior pituitary cells, and 40–50% of these cells were GH-positive. No such immunostaining was seen with sera from healthy controls. The APS1 Aab-positive, GH-negative cells may represent a novel subpopulation of anterior pituitary cells. In addition, 4/6 patient sera showed staining of a fiber-plexus in the pituitary intermediate lobe recognizing enzymes of monoamine and GABA synthesis. Thus, we have identified TDRD6 as a major autoantigen in APS1 patients and shown that several sera from GH-deficient patients stain specific cell populations and nerves in the pituitary gland.
Bensing, Sophie; Fetissov, Serguei O.; Mulder, Jan; Perheentupa, Jaakko; Gustafsson, Jan; Husebye, Eystein S.; Oscarson, Mikael; Ekwall, Olov; Crock, Patricia A.; Hokfelt, Tomas; Hulting, Anna-Lena; Kampe, Olle
It is well known that patients suffering from an autoimmune disease are more prone to develop another one, too. The authors have previously shown frequent occurrence of celiac disease in patients with type 1 diabetes mellitus compared to the background population. Autoimmune thyroid disease, the most common autoimmune disease associated with type 1 diabetes mellitus, generally occurs after the manifestation of diabetes, in the second decade of life. The aim of the study was to investigate the prevalence of thyroid autoimmunity as well as the frequency of autoimmune thyroid disease in patients with type 1 diabetes mellitus. Their aim was also to compare the prevalence of autoimmune thyroid disease in patients with type 1 diabetes mellitus and in those with type 1 diabetes mellitus and celiac disease. Methods: Screening was performed in 268 patients with type 1 diabetes mellitus alone and in 48 children with type 1 diabetes mellitus and celiac disease, with anti-peroxidase and anti thyroglobulin antibody. In case of autoantibody positivity, testing thyroid function and ultrasonography confirmed the autoimmune thyroid disease. According to the results, frequency of autoantibody positivity was significantly higher in diabetic patients suffering from celiac disease (type 1 diabetes mellitus: 43 (16%), type 1 diabetes mellitus + celiac disease: 16 (33,3%), p < 0,01). Hypothyroidism due to thyroiditis was also more prevalent in patients with type 1 diabetes mellitus and celiac disease. Conclusions: Due to increased risk, the authors emphasise the need of frequent screening for autoimmune thyroid disorder in patients with type 1 diabetes mellitus and celiac disease. PMID:18292034
Körner, Anna; Tóth-Heyn, Péter; Dezsofi, Antal; Veres, Gábor; Madácsy, László; Arató, András
Group A streptococcal infections cause a wide range of neuropsychiatric disorders, such as Sydenham's chorea, tics, obsessive-compulsive disorders, and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography, single-photon emission computed tomography) imaging studies in patients with Sydenham's chorea have suggested reversible striatal abnormalities. The objective of this
Elvan Caglar Citak; Kivilcim Gücüyener; Nese Ilgin Karabacak; Ayse Serdaroglu; Cetin Okuyaz; Kursad Aydin
Chronic mucocutaneous candidiasis is an immunodeficiency disease characterized by T-cell dysregulation and chronic superficial candidal infections. We report on three patients with chronic mucocutaneous candidiasis who developed autoantibodies to erythrocytes. Our first patient, a 19-year-old female, developed autoimmune hemolytic anemia (AIHA) that required multiple courses of treatment, including corticosteroids, intravenous immunoglobulin, and danazol. During the last exacerbation of AIHA, intensive treatment with corticosteroids and intravenous immunoglobulin failed and yet the patient responded to plasmapheresis. Our second patient, a 21-year-old male, developed AIHA which responded to oral corticosteroid therapy. Our third patient, a 6-year-old female without evidence of hemolysis, was found to have erythrocyte autoantibodies on routine screening. These three patients had positive direct antiglobulin tests, and the first patient had both immunoglobulin G (IgG) and IgM erythrocyte autoantibodies, while the remaining two patients had only IgG autoantibody. This is the first report of the association of AIHA with chronic mucocutaneous candidiasis. We suggest that all patients with chronic mucocutaneous candidiasis be screened periodically for erythrocyte autoantibodies. Plasmapheresis, a safe ancillary procedure in the management of AIHA, may be life-saving in some cases. The occurrence of erythrocyte autoantibodies in mucocutaneous candidiasis may be related to immunoregulatory disorders in this disease.
Oyefara, B I; Kim, H C; Danziger, R N; Carroll, M; Greene, J M; Douglas, S D
The spectrum of autoimmune optic neuropathies (ON) is extending. The phenotypic spectrum includes single isolated optic neuritis (SION), relapsing isolated optic neuritis (RION), chronic relapsing inflammatory optic neuropathy (CRION), the neuromyelitis optica (NMO) spectrum disorder, multiple sclerosis associated optic neuritis (MSON) and unclassified optic neuritis (UCON) forms. Epidemiological data suggests a slight female predominance. The ethnic heritage is relevant as Caucasian patients are more likely to suffer from MSON, whilst SION, RION, CRION and NMO are more frequent in non-Caucasian patients. Importantly, prognosis for recovery of visual function is good in MSON, but poorer in NMO and CRION which also have a high chance for recurrent episodes. Testing for serum anti-AQP4 autoantibodies is advised in all patients with severe, atypical or recurrent ON because of the high diagnostic specificity. The diagnostic specificity may be aided by testing for glial biomarkers in the CSF and prognostic accuracy by testing for biomarkers for neuroaxonal degeneration. Optical coherence tomography is a highly accurate tool to document the final outcome. The current clinical classification criteria rely on the phenotype, response to treatment and presence of anti-AQP4 autoantibodies. PMID:24424177
Petzold, Axel; Plant, Gordon T
CTLA-4, initially described as a membranebound molecule, is a costimulatory receptor transducing a potent inhibitory signal.\\u000a Increasing evidence shows the CTLA-4 gene to be an important susceptibility locus for autoimmune endocrinopathies and other autoimmune disorders. A soluble form\\u000a of cytotoxic T-lymphocyte-associated antigen-4 (sCTLA-4) has been established and shown to possess CD80\\/CD86 binding activity\\u000a and in vitro immunoregulatory functions. sCTLA-4 is
Daniele Saverino; Rita Simone; Marcello Bagnasco; Giampaola Pesce
Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder of the immune system caused by inadequate induction of apoptosis via the Fas pathway, mainly characterized by generalized lymphadenopathy, splenomegaly, and autoimmune cytopenias, as well as increased risk of lymphoma. Although the clinical course of ALPS is highly variable, without treatment long-term prognosis is unsatisfactory for most patients. ALPS has been treated with most of the existing immunosuppressive agents, with variable success. We hereby present a case of a child with ALPS whose greatly enlarged lymph nodes rapidly regressed upon initiation of rapamycin, a novel potential therapeutic agent in the treatment of ALPS. PMID:19588524
Jani?, Mihailo Dragana; Brasanac, Cedomir Dimitrije; Jankovi?, Jovan Srda; Dokmanovi?, Bogdan Lidija; Krstovski, Radmio Nada; Kraguljac Kurtovi?, Janko Nada
It is increasingly recognized that organs beyond the pancreas may be clinically involved in patients with autoimmune pancreatitis (AIP). Other gastrointestinal sites (such as the extrapancreatic biliary tree, liver, and ampulla) appear particularly affected, but involvement of many other organs (including kidneys, lungs, retroperitoneum, and brain) is increasingly reported. A similar histological lesion, characterized by an IgG4-positive lymphoplasmacytic infiltrate, affects both the pancreas and extrapancreatic tissues, strongly suggesting an aetiopathogenic link. In this review we discuss the clinical presentation and disease course, diagnostic features, and management of extrapancreatic involvement in AIP. PMID:19212307
Webster, G J M; Deheregoda, M G; Church, N I
Autoimmune bullous diseases result from an immune response to molecular components of the desmosome or basement membrane. Bullous diseases are associated with a high degree of morbidity and occasional mortality. Therapy of bullous diseases consists of suppressing the immune system, controlling inflammation and improving healing of erosions. The therapeutic agents used in the treatment of bullous diseases may be associated with high morbidity and occasional mortality. Successful treatment requires understanding of the pathophysiology of the disease process and the pharmacology of the drugs being used.
Mutasim, Diya F
\\u000a Human immunoglobulin receptors (FcR) provide an important link between the humoral and cellular branches of the immune response.\\u000a FcR engagement in autoimmune diseases may result in many biological responses including phagocytosis, endocytosis, antibody-dependent\\u000a cellular cytotoxicity (ADCC), release of inflammatory mediators, facilitation of antigen presentation and clearance of immune\\u000a complexes (IC). Most FcR belong to the family of multi-chain immune recognition
R. Repp; J. G. J. Winkel
The aim of this study was to determine if the prevalence of autoimmune disorders in the relatives of patients with systemic lupus erythematosus (SLE) is greater than that of relatives of patients with juvenile rheumatoid arthritis (JRA). Interviews were used to obtain histories of the following autoimmune disorders among living or deceased first-, second-, and third-degree relatives of 91 SLE and 110 JRA families: ankylosing spondylitis, SLE, rheumatoid arthritis (RA), JRA, multiple sclerosis, juvenile dermatomyositis, Sjögren's syndrome, myasthenia gravis, psoriasis, and thyroid diseases. There were statistically significant differences between the SLE and JRA probands in mean age and gender ratio (19.1 +/- 4.8 vs 14.0 +/- 5.5 years; M (male)/F (female): 17/74 vs 62/48, p<0.005). The prevalence rate of autoimmune diseases in relatives of SLE families (20.9%) was greater than in JRA families (11.8%), but not statistically significantly so. The mean age (18.0 +/- 5.3 vs 14.0 +/- 4.3 years), mean age at diagnosis (13.4 +/- 4.3 vs 7.9 +/- 3.9 years) and gender ratio (F/M, 16/3 vs 5/8) of the patients with affected relatives between these 2 groups all had statistically significant differences. A higher prevalence of SLE in relatives was found in SLE families than in JRA cases. Furthermore, this study revealed a higher incidence of autoimmune disorders among second- and third-degree relatives of SLE or JRA probands versus first-degree ones, especially sisters (including 1 pair of twins) and the maternal aunt in SLE families. These data demonstrate that the prevalence of autoimmune disorders in the relatives of patients with SLE is greater than those of relatives of patients with JRA. This suggests that clinically different autoimmune phenotypes may share common susceptibility genes, which may act as risk factors for autoimmunity. PMID:15181489
Huang, Chun-Mei; Yang, Yao-Hsu; Chiang, Bor-Luen
Immune responses against foreign antigens are initiated and controlled by dendritic cells (DCs). Accumulating evidence suggests that autoimmunity, involving T cells directed against self, can also be primed by DCs. We propose that DCs could induce autoimmunity following their differentiation by certain cytokines, or because of intrinsic defects in genes controlling DC function. Both processes result in DCs that behave
Hal Drakesmith; Benjamin Chain; Peter Beverley
Objective. To investigate evidence of an association between school teaching and mortality from autoimmune diseases. Methods. A proportional mortality study using US death certificates from the 1985-95 period was conducted. Death certificates that listed elementary or secondary school teaching as the usual occupation were identified, as were those that cited any of 13 autoimmune diseases as a cause of death.
STEPHEN J. WALSH; LAURIE M. DeCHELLO
BACKGROUND: Autoimmune diseases may selectively affect women in their reproductive years, and conversely, pregnancy may affect the expression of autoimmune disease. This review addresses the impact of abnormal autoim- munity on female fertility, premature ovarian failure (POF) and recurrent pregnancy loss, as well as the influence of pregnancy in systemic lupus erythematosus (SLE). METHODS: From a PubMed search, citations were
Ricard Cervera; Juan Balasch
Autoimmune cytopenias are typical paraneoplastic phenomena in malignant lymphomas. We assessed the occurrence, clinical, and laboratory features as well as the response to treatment of autoimmune hemolytic anemia, autoimmune thrombocytopenia, and neutropenia in published cases of Hodgkin lymphomas (HL). We identified 34 cases of an association between HL and autoimmune hemolytic anemia and 48 cases of an association of autoimmune thrombocytopenia (AITP) and HL. The autoimmune cytopenias (AIC) may occur prior to, concurrent with, at the time of recurrence of lymphoma or in complete remission after treatment. Almost all autoimmune hemolytic anemias were caused by warm antibodies. Patients with HL with AIC are more commonly males and are more likely to have mixed cellularity (MC) HL. HL is the only lymphoma which may be associated with autoimmune neutropenia. In contrast to AIC in diffuse large B-cell lymphoma (DLBCL), early stage is less common in patients with HL with AIC. AIC in HL respond better to antilymphoma treatment than to steroids, with the exception of post-treatment AITP in CR of HL which responds easily and durably to steroids. PMID:20141438
Lechner, Klaus; Chen, Yen-An
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
AIMS: To study the distribution of tenascin by immunocytochemistry in autoimmune diseases of the thyroid. METHODS: Thyroids from patients with inflammatory lesions of the thyroid (lymphocytic thyroiditis Hashimoto, Grave's disease, thyroiditis DeQuervain) were studied by immunocytochemistry using antibodies against tenascin, collagen III, and collagen IV. RESULTS: In autoimmune lymphocytic thyroiditis Hashimoto there was a characteristic corona-like staining pattern of tenascin
W Back; C Heubner; J Winter; U Bleyl
Macrophage activation syndrome (MAS) is a phenomenon characterized by cytopenia, organ dysfunction, and coagulopathy associated with an inappropriate activation of macrophages. Current diagnostic criteria are imprecise, but the syndrome is now recognized as a form of hemophagocytic lymphohistiocytosi