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1

Autoimmune thyroid disorders.  

PubMed

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

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

2015-02-01

2

Emerging therapies for autoimmune disorders.  

PubMed

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

Zack, Eric

2014-01-01

3

The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease  

PubMed Central

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. PMID:21304144

Kayser, Matthew S.; Dalmau, Josep

2011-01-01

4

Epilepsy associated with systemic autoimmune disorders.  

PubMed

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

2013-03-01

5

Vitamin D and autoimmune rheumatologic disorders.  

PubMed

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

2010-05-01

6

Natural killer cells in human autoimmune disorders  

PubMed Central

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

2013-01-01

7

Autoimmune thyroid disorders and coeliac disease.  

PubMed

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

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

1994-02-01

8

Neuromyelitis optica spectrum disorders without and with autoimmune diseases  

PubMed Central

Background Neuromyelitis optica spectrum disorder (NMOSD) can coexist with non-organ-specific or organ-specific autoimmune diseases. The aim of this study was to investigate and compare the features between NMOSD without and with autoimmune diseases, and NMOSD with non-organ-specific and organ-specific autoimmune diseases. Methods One hundred and fifty five NMOSD patients without autoimmune diseases (n?=?115) and with autoimmune diseases (n?=?40) were enrolled. NMOSD with autoimmune diseases were divided by organ-specific autoimmune diseases. The clinical, laboratory and magnetic resonance imaging features between two groups were assessed. Results Motor deficit was less frequent in NMOSD patients with non-organ-specific autoimmune diseases (p?=?0.024). Cerebrospinal fluid white blood cell and protein, serum C-reactive protein and immunoglobulin G were lower in NMOSD patients without autoimmune diseases, while several autoantibodies seropositivity and thyroid indexes were significantly higher in NMOSD patients with autoimmune diseases (p??0.05). NMOSD patients with autoimmune diseases had higher brain abnormalities than NMOSD without autoimmune diseases (p?autoimmune diseases were similar. NMOSD with autoimmune diseases have high frequency of brain abnormalities. PMID:25135481

2014-01-01

9

Autoimmune haematological disorders in two Italian children with Kabuki Syndrome  

PubMed Central

Kabuki syndrome (also called Niikawa-Kuroki syndrome) is a rare genetic disease described for the first time in Japan, characterised by anomalies in multiple organ systems and often associated with autoimmune disorders and impaired immune response. We herein report the clinical history, the therapeutic approach and the outcome of two children with Kabuki syndrome who developed autoimmune haematological disorders (haemolytic anaemia and immune thrombocytopenia). Factors regarding differential diagnosis and interventions in better management of this syndrome and its complications are discussed. This is the first report of Italian children with autoimmune haematological disorders complicating Kabuki syndrome. PMID:24460868

2014-01-01

10

Autoimmune polyendocrine syndromes.  

PubMed

Autoimmune polyendocrine syndromes (APS), also called polyglandular autoimmune syndromes (PGAS), are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organs, although non-endocrine organs can be affected. The two major autoimmune polyendocrine syndromes, (type1-type2/APS-1 and APS-2), both have Addison's disease as a prominent component. Further autoimmune polyendocrine syndromes include APS3 and APS4. The major autoimmune polyendocrine syndromes have a strong genetic component with the type 2 syndrome occurring in multiple generations and the type I syndrome in siblings. It is well recognized that more than 20years may elapse between the onset on one endocrinopathy and the diagnosis of the next, for example, almost 40-50% of subjects with Addison's disease will develop an associated endocrinopathy. The discovery of the polyendocrine autoimmune syndromes offered the possibility to understand autoimmune disorders with particular interest for type 1A diabetes and the neuroendocrine immunology (NEI) is further contributing to understand the links. PMID:24055063

Cutolo, Maurizio

2014-02-01

11

[Autoimmune thyroid disorders and reproductive failures].  

PubMed

At recent ten years have concluded influence of thyroid autoantibodies in normal beginning, development and growing up of pregnancy. Changing in thyroid autoimmunity, even in the absence of evident thyroid dysfunction, is associated with an increased risk of subfertility. The disturbances in thyroid autoimmunity have associated with a significantly increased risk of recurrent pregnancy loss. Although of pathophysiologic mechanism is still not unclear has suggested that thyroid autoantibodies started abnormal immune response and following disturbances in maternal-fetal thyroid function. This can easily be prevented by systematic screening, for thyroid dysfunction and antibody presence during early gestation, followed by the administration of levothyroxine treatment. PMID:20380094

Todorova-Ananieva, K

2009-01-01

12

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

PubMed

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

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

2015-01-01

13

Pediatric autoimmune enteropathy: an entity frequently associated with immunodeficiency disorders.  

PubMed

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

2014-04-01

14

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

PubMed

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

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

2014-01-01

15

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

PubMed

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

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

2014-12-01

16

Movement disorders in paraneoplastic and autoimmune disease  

PubMed Central

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

Panzer, Jessica; Dalmau, Josep

2013-01-01

17

Neuromyelitis optica spectrum disorders associated with other autoimmune diseases.  

PubMed

Neuromyelitis optica (NMO) is an inflammatory demyelinating autoimmune disease with severe, tremendously incapacitating, consequences in the patient's health and wellbeing. Until 2004, NMO was considered a restricted type of multiple sclerosis but in the same year an auto-antibody reacting against aquaporin-4 (NMO-IgG) was found to be related with NMO and it was considered the main etiologic agent of this disease. Its detection is very sensitive and specific allowing an early diagnosis and a better treatment and prognosis. With this tool, a spectrum of diseases including other autoimmune diseases was found to have NMO-IgG antibodies and a new classification named NMO spectrum disorders was created. In this review, we sum up the developments in this field associated with other autoimmune diseases. We approach the latest discoveries in the diagnosis like the new biomarkers that will possibly be used in the close future or the developments in the neuroimaging techniques. We reviewed the literature and synthesized case reports of NMO patients with concurrent autoimmune diseases and the information from useful larger studies. Finally, we summarize the commonly used treatments in NMO and we try to specify the best treatment for NMO with simultaneous autoimmune disease. This review updates the information about this issue and raises the awareness of rheumatologists for these severe diseases. PMID:24952418

Freitas, Eduardo; Guimarăes, Joana

2015-02-01

18

Association between autoimmune thyroiditis and depressive disorder in psychiatric outpatients.  

PubMed

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

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

2015-02-01

19

Inhibiting ROR?t/Th17 axis for autoimmune disorders.  

PubMed

The recent success reported in late-stage clinical trials for the treatment of psoriasis by antibodies directed against interleukin (IL)-17 or its receptor has validated and strongly supports the development of inhibitors of the IL-17 pathway as a new therapeutic modality in chronic inflammation and autoimmunity. These results also encourage the drug discovery of orally available small molecules that can modulate down the production of IL-17 by Th17 cells (the major IL-17 producers) or the downstream signaling of the IL-17 receptor. Here, we review these strategies with an emphasis on inhibiting the retinoic-acid-related orphan nuclear receptor ROR?t, which is the master regulator of Th17 cells and a promising therapeutic target for the treatment of multiple autoimmune disorders. PMID:24792721

Isono, Fujio; Fujita-Sato, Saori; Ito, Shuichiro

2014-08-01

20

Metabolic disorders and nutritional status in autoimmune thyroid diseases.  

PubMed

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

Kawicka, Anna; Regulska-Ilow, Bo?ena; Regulska-Ilow, Bo?ena

2015-01-01

21

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

ERIC Educational Resources Information Center

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

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

2012-01-01

22

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

PubMed

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

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

2014-12-01

23

Primary Immune Deficiency Disorders Presenting as Autoimmune Diseases: IPEX and APECED  

Microsoft Academic Search

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

2008-01-01

24

[Use of intravenous polyclonal immunoglobulins in autoimmune and inflammatory disorders].  

PubMed

Initially used for the treatment of immunodeficiencies, intravenous immunoglobulins (IVIg) have increasingly been used as immunomodulatory agent in autoimmune and inflammatory disorders. The mode of action of IVIg is enigmatic, probably involving Fc-dependent and/or F(ab')2-dependent non-exclusive mechanisms of action. IVIg broadly interacts with the different components of the immune system: cytokines, complement, Fc receptors and several cell surface immunocompetent molecules. IVIg also has an impact on effector functions of immune cells. These mechanisms of action of IVIg reflect the importance of natural antibodies in the maintenance of immune homeostasis. We discuss here the recent advances in the understanding of immunoregulatory effects of IVIg, and we pointed out the need of new strategies to overcome the predicted increasing worldwide shortage of IVIg. PMID:17498995

Graff-Dubois, Stéphanie; Sibéril, Sophie; Elluru, Sriramulu; Negi, Vir-Singh; Delignat, Sandrine; Mouthon, Luc; Lacroix-Desmazes, Sébastien; Kazatchkine, Michel D; Bayary, Jagadeesh; Kaveri, Srini V

2007-05-01

25

Myelodysplastic Syndromes (MDS) and autoimmune disorders (AD): cause or consequence?  

PubMed

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

2013-12-01

26

Useful biomarkers for assessment of hepatitis C virus infection-associated autoimmune disorders  

PubMed Central

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. PMID:24659887

Yang, Deng-Ho; Ho, Ling-Jun; Lai, Jenn-Haung

2014-01-01

27

Paraneoplastic and other autoimmune disorders of the central nervous system.  

PubMed

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

McKeon, Andrew

2013-04-01

28

Paraneoplastic and Other Autoimmune Disorders of the Central Nervous System  

PubMed Central

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

McKeon, Andrew

2013-01-01

29

TGF-?/BMPs: crucial crossroad in neural autoimmune disorders.  

PubMed

Transforming growth factor beta (TGF-?) has a crucial role in the differentiation of ectodermal cells to neural or epidermal precursors. TGF-? and bone morphogenetic protein molecules (BMPs) are involved in many developmental processes, including cell proliferation and differentiation, apoptosis, mitotic arrest and intercellular interactions during morphogenesis. Additionally, the failure of central thymic tolerance mechanisms, leading to T cells with a skewed autoreactive response, is being described as a contributor in inflammatory processes in autoimmune diseases such as multiple sclerosis. Since TGF-? and BMP proteins are crucial for the development of the neural system and the thymus, as well as for the differentiation of T cells, it is essential to further investigate their role in the pathophysiology of this disorder by using references from embryonic experimental research. Available literature in the TGF/BMP signalling cascade, mostly during embryonic development of the nervous system is being reviewed. An attempt is made to further elucidate a potential role of TGF/BMP signalling in the pathophysiology of MS. During demyelination, BMP signaling, through various molecular mechanisms, directs the development of the adult neural stem cell in the astrocyte rather than the oligodendrocyte direction, therefore inhibiting the repair process. Further understanding of the above relationships could lead to the development of potentially efficient therapies for MS in the future. PMID:21718734

Voumvourakis, Konstantine I; Antonelou, Roubina Ch; Kitsos, Dimitrios K; Stamboulis, Eleftherios; Tsiodras, Sotirios

2011-10-01

30

Type 1 diabetes and polyglandular autoimmune syndrome: A review  

PubMed Central

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

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

2015-01-01

31

Type 1 diabetes and polyglandular autoimmune syndrome: A review.  

PubMed

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

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

2015-02-15

32

The Increased Risk for Autoimmune Diseases in Patients with Eating Disorders  

PubMed Central

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

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

2014-01-01

33

Practical considerations on the use of rituximab in autoimmune neurological disorders  

PubMed Central

Rituximab (Mabthera, Rituxan) is a chimeric human/murine monoclonal antibody against CD-20 surface antigen expressed on B-cells. Rituximab, by causing B-cell depletion, appears to be effective in several autoimmune disorders; it has been approved for rheumatoid arthritis and is a promising new agent in the treatment of several autoimmune neurological disorders. A controlled study in patients with relapsing remitting multiple sclerosis has shown that rituximab significantly reduces the number of new MRI lesions and improves clinical outcome; it also showed some promise in a subset of patients with primary progressive MS. The drug is also effective in a number of patients with Devic’s disease, myasthenia gravis, autoimmune neuropathies, and inflammatory myopathies. The apparent effectiveness of rituximab has moved B-cells into the center stage of clinical and laboratory investigation of autoimmune neurological disorders. We review the evidence-based effectiveness of rituximab in neurological disorders based on controlled trials and anecdotal reports, including our own experience, and address the immunobiology of B-cells in autoimmune central nervous system (CNS) and peripheral nervous system (PNS) disorders. In addition, we provide practical guidelines on how best to use this drug in clinical practice and highlight its potential toxicity. PMID:21179602

Kosmidis, Mixalis L.; Dalakas, Marinos C.

2010-01-01

34

An inherited disorder of lymphocyte apoptosis: the autoimmune lymphoproliferative syndrome.  

PubMed

The autoimmune lymphoproliferative syndrome (ALPS) affords novel insights into the mechanisms that regulate lymphocyte homeostasis and underlie the development of autoimmunity. This syndrome arises early in childhood in persons who inherit mutations in genes that mediate apoptosis, or programmed cell death. The timely deletion of lymphocytes is a way to prevent their accumulation and the persistence of cells that can react against the body's own antigens. In ALPS, defective lymphocyte apoptosis permits chronic, nonmalignant adenopathy and splenomegaly; the survival of normally uncommon "double-negative" CD3+ CD4- CD8- T cells; and the development of autoimmune disease. Most cases of ALPS involve heterozygous mutations in the lymphocyte surface protein Fas that impair a major apoptotic pathway. Detailed immunologic investigations of the cellular and cytokine profiles in ALPS show a prominent skewing toward a T-helper 2 phenotype; this provides a rational explanation for the humoral autoimmunity typical of patients with ALPS. Prospective evaluations of 26 patients and their families show an ever-expanding spectrum of ALPS and its major complications: hypersplenism, autoimmune hemolytic anemia, thrombocytopenia, and neutropenia. Defective apoptosis may also contribute to a heightened risk for lymphoma. PMID:10189330

Straus, S E; Sneller, M; Lenardo, M J; Puck, J M; Strober, W

1999-04-01

35

[Type i polyglandular autoimmune syndrome associated with C322fsx372 mutation].  

PubMed

Polyglandular autoimmune syndromes are rare diseases based on autoimmune mechanisms in which endocrine and non-endocrine disorders coexist. In type 1 the characteristic manifestations are chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. A case is presented of a patient with typical clinical sequence, along with other changes, and in whom a mutation in homozygosis, C322fsX372, was detected after performing a molecular analysis of autoimmunity regulator gene (AIRE). Inheritance is autosomal recessive, associated with mutations in the AIRE gene, which encodes a protein involved in autoimmunity and immunodeficiency. For diagnosis, At least two of the three major clinical manifestations are required for a diagnosis. However, only one of them is necessary in the study of relatives of affected patients. These syndromes must be diagnosed early, given their high morbidity and mortality. Every manifestation needs to be treated, in order to maintain the quality of life. PMID:24582129

Roncalés-Samanes, P; de Arriba Muńoz, A; Lou Francés, G M; Ferrer Lozano, M; Justa Roldán, M L; Labarta Aizpun, J I

2015-01-01

36

IVIg in other autoimmune neurological disorders: current status and future prospects.  

PubMed

A number of autoimmune disorders have been identified in which IVIg treatment may be beneficial. Evidence for the use of IVIg in inflammatory myopathies comes from controlled trials in dermatomyositis (DM) and sporadic-inclusion body myositis (s-IBM). In DM, muscle strength was increased and neuromuscular scores and skin rashes improved. Results for s-IBM have not been as encouraging as those observed for DM. Subsequently, IVIg should be recommended as a second-line therapy in DM and used for life-threatening dysphagia in s-IBM. Using an animal model of experimental autoimmune myasthenia gravis (MG), studies also indicate that IVIg can significantly improve clinical symptoms and affect pathogenic idiotypic antibodies. In human MG, studies indicate that IVIg exhibited equal efficacy compared to plasmapheresis. IVIg can therefore be recommended for use in an MG crisis or in lieu of plasmapheresis. The role of IVIg in the chronic management of MG has not been studied. IVIg has also been investigated in autoimmune CNS disorders. In a controlled study in patients with stiff person syndrome IVIg was effective, with improvements in the distribution of stiffness index and heightened sensitivity scores. For neurodegenerative diseases such as Alzheimer's disease, post-polio syndrome, pain, fibrosis, and autoimmune sleep disorders, some early promising results for the use of IVIg are emerging, but remain to be fully investigated. In conclusion, IVIg appears to be an effective treatment for a number of autoimmune disorders, however, optimal dosing and pharmacogenetic studies are necessary. PMID:18685921

Dalakas, Marinos

2008-07-01

37

Peripheral blood dendritic cells in alcoholic and autoimmune liver disorders  

Microsoft Academic Search

Little is known about effects of alcohol consumption on dendritic cell (DC) function and resultant immune response. However, quantitative and qualitative disturbances of DCs are speculated to be involved in alcohol-related as well as in other liver pathology. The present study aimed to evaluate changes in circulating DC subsets in alcoholic liver disease (N = 43), autoimmune hepatitis (N =

A Zwolak; I Jastrz?bska; A Surdacka; B Kasztelan-Szczerbi?ska; J Roli?ski; B Skrzyd?o-Radoma?ska; P Radwan; J Daniluk

2012-01-01

38

An ion channel chip for diagnosis and prognosis of autoimmune neurological disorders.  

PubMed

Autoantibodies directed against ion channels and ionotropic receptors are associated with neuromuscular and neurological disorders. Their detection has proven to be useful for diagnosis, prognosis and treatment of these autoimmune syndromes. We have designed an ion channel chip for the systematic and rapid screening of antibodies directed against tens of different ion channels. The chip has been validated by confirming the presence of autoantibodies in patients with anti-NMDA receptor encephalitis. Such a chip will be useful for the diagnosis of already documented disorders, but also to identify new targets of autoimmunity and classification of the corresponding diseases. The article presents some promising patents on the Ion Channel Chip. PMID:24050250

Chatelain, Franck C; Mazzuca, Michel; Larroque, Marie-Madeleine; Rogemond, Veronique; Honnorat, Jerome; Lesage, Florian

2013-12-01

39

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

PubMed Central

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

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

2011-01-01

40

Takotsubo Cardiomyopathy in a Patient With Multiple Autoimmune Disorders and Hyperthyroidism  

PubMed Central

Takotsubo cardiomypathy is a very rare cardiovascular syndrome leading to myocardial infarction and left ventricular dysfunction in the absence of a detectable coronary artery lesion. It is accepted as reversible left ventricular asynergy occuring typically after an intrinsic adrenergic hyperstimulation. In this report we present Takotsubo cardiomyopathy in a 75-year-old patient with multiple autoimmune disorders. PMID:25478511

Ugurlucan, Murat; Zorman, Yilmaz; Ates, Gursel; Arslan, Ahmet H.; Yildiz, Yahya; Karahan Zor, Aysegul; Cicek, Sertac

2013-01-01

41

Peripheral blood dendritic cells in alcoholic and autoimmune liver disorders.  

PubMed

Little is known about effects of alcohol consumption on dendritic cell (DC) function and resultant immune response. However, quantitative and qualitative disturbances of DCs are speculated to be involved in alcohol-related as well as in other liver pathology. The present study aimed to evaluate changes in circulating DC subsets in alcoholic liver disease (N = 43), autoimmune hepatitis (N = 26) and primary biliary cirrhosis (N = 20). DCs isolated from the peripheral blood of recruited participants were stained with monoclonal antibodies against blood dendritic cell antigens (BDCAs) and estimated using the flow cytometry. Myeloid DCs were defined as BDCA-1(+)/CD19(-) cells, and lymphoid DCs as BDCA-2(+)/CD123(+) cells. Total numbers of circulating DCs in subjects with some liver diseases were markedly lower than in the healthy participants (p = 0.03). There was a significantly lower percentage of circulating BDCA-2(+)/CD123(+) (p = 0.02), and a tendency for the percentage of circulating BDCA-1(+)/CD19(-) cells to decrease in patients with liver diseases compared to the controls (p = 0.09). These results may suggest that decreased numbers of DCs may be responsible for reduced adaptive immune responses and increased susceptibility to infections and cancer development observed in patients exposed to alcohol. Moreover, numerical abnormalities of DCs may contribute to the breakdown of self-tolerance, a feature of autoimmune diseases. PMID:22076495

Zwolak, A; Jastrzebska, I; Surdacka, A; Kasztelan-Szczerbi?ska, B; ?ozowski, C T; Roli?ski, J; Skrzyd?o-Radoma?ska, B; Radwan, P; Daniluk, J

2012-05-01

42

Acquired Hemophilia A: A Frequently Overlooked Autoimmune Hemorrhagic Disorder  

PubMed Central

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

Takeda, Tomohiro

2014-01-01

43

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

PubMed Central

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

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

2014-01-01

44

A close association of autoimmune-mediated processes and autoimmune disorders with chronic myelomonocytic leukemia: observation from a single institution.  

PubMed

Chronic myelomonocytic leukemia (CMML), a clonal hematopoietic stem cell disease, may be linked to immune-mediated processes and/or autoimmune disorders (AID), although the exact pathogens are still elusive. We retrospectively analyzed 123 CMML patients in our institution. Twenty-four CMML patients (19.5%) had at least one immune-mediated disorder, most commonly idiopathic thrombocytopenic purpura, gout and psoriasis. Four of these 24 patients (15%) had more than one AID. We found that, in contrast to the general population with a prevalence rate of 3.2-5.2%, newly diagnosed CMML patients demonstrated a high prevalence and variety of immune-mediated processes and/or AID. When we compared the results with those of myelodysplastic syndromes published in the literature, the prevalence of AID in these two groups of patients is similar. Our results also showed that the presence of cytogenetic abnormalities was less in CMML patients with AID (6 of 21; 28.6%) than in those without AID (37 of 94; 39.4%), although there was no statistical significance (p = 0.334). A multicenter large cohort study of CMML with AID is recommended to illustrate the molecular relationship between the two distinct groups. © 2014 S. Karger AG, Basel. PMID:25413011

Peker, Deniz; Padron, Eric; Bennett, John M; Zhang, Xiaohui; Horna, Pedro; Epling-Burnette, Pearlie K; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; Moscinski, Lynn; List, Alan F; Komrokji, Rami S; Zhang, Ling

2015-01-01

45

PEST family phosphatases in immunity, autoimmunity, and autoinflammatory disorders.  

PubMed

The proline-, glutamic acid-, serine- and threonine-rich (PEST) family of protein tyrosine phosphatases (PTPs) includes proline-enriched phosphatase (PEP)/lymphoid tyrosine phosphatase (LYP), PTP-PEST, and PTP-hematopoietic stem cell fraction (HSCF). PEP/LYP is a potent inhibitor of T-cell activation, principally by suppressing the activity of Src family protein tyrosine kinases (PTKs). This function seems to be dependent, at least in part, on the ability of PEP to bind C-terminal Src kinase (Csk), a PTK also involved in inactivating Src kinases. Interestingly, a polymorphism of LYP in humans (R620W) is a significant risk factor for autoimmune diseases including type 1 diabetes, rheumatoid arthritis, and lupus. The R620W mutation may be a 'gain-of-function' mutation. In non-hematopoietic cells, PTP-PEST is a critical regulator of adhesion and migration. This effect correlates with the aptitude of PTP-PEST to dephosphorylate cytoskeletal proteins such as Cas, focal adhesion associated-kinase (FAK), Pyk2, and PSTPIP. While not established, a similar function may also exist in immune cells. Additionally, overexpression studies provided an indication that PTP-PEST may be a negative regulator of lymphocyte activation. Interestingly, mutations in a PTP-PEST- and PTP-HSCF-interacting protein, PSTPIP1, were identified in humans with pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome and familial recurrent arthritis, two autoinflammatory diseases. These mutations abrogate the ability of PSTPIP1 to bind PTP-PEST and PTP-HSCF, suggesting that these two PTPs may be negative regulators of inflammation. PMID:19290936

Veillette, André; Rhee, Inmoo; Souza, Cleiton Martins; Davidson, Dominique

2009-03-01

46

Styles of adaptation in autoimmune thyroiditis and bipolar disorder: a pilot study  

Microsoft Academic Search

Background: A growing body of evidence suggests that styles of adaptation, assessed with the Serial Color-Word Test (S-CWT, a 5-trials Stroop task), are able to differentiate several mental and psychosomatic disorders. Recent findings have confirmed a very high rate of cases of autoimmune thyroiditis (so called Hashimoto disease) among bipolar patients, suggesting an etio-pathogenetic relatedness between the two ailments. Based

I. Alex Rubino; Giacomo Salvadore; Alberto Siracusano; Enrico Fidotti; Paolo Zuppi

2004-01-01

47

Autoimmune liver disease panel  

MedlinePLUS

Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

48

Design of Peptide Immunotherapies for MHC Class-II-Associated Autoimmune Disorders  

PubMed Central

Autoimmune disorders, that occur when autoreactive immune cells are induced to activate their responses against self-tissues, affect one percent of the world population and represent one of the top 10 leading causes of death. The major histocompatibility complex (MHC) is a principal susceptibility locus for many human autoimmune diseases, in which self-tissue antigens providing targets for pathogenic lymphocytes are bound to HLA molecules encoded by disease-associated alleles. In spite of the attempts to design strategies for inhibition of antigen presentation targeting the MHC-peptide/TCR complex via generation of blocking antibodies, altered peptide ligands (APL), or inhibitors of costimulatory molecules, potent therapies with minimal side effects have yet to be developed. Copaxone (glatiramer acetate, GA) is a random synthetic amino acid copolymer that reduces the relapse rate by about 30% in relapsing-remitting multiple sclerosis (MS) patients. Based on the elucidated binding motifs of Copaxone and of the anchor residues of the immunogenic myelin basic protein (MBP) peptide to HLA-DR molecules, novel copolymers have been designed and proved to be more effective in suppressing MS-like disease in mice. In this report, we describe the rationale for design of second-generation synthetic random copolymers as candidate drugs for a number of MHC class-II-associated autoimmune disorders. PMID:24324511

2013-01-01

49

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

PubMed Central

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

Rhee, Hanna; Cameron, Daniel J

2012-01-01

50

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

PubMed

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

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

2014-07-14

51

Autoimmune disorders  

MedlinePLUS

... sprue (gluten-sensitive enteropathy) Dermatomyositis Graves' disease Hashimoto's thyroiditis Multiple sclerosis Myasthenia gravis Pernicious anemia Reactive arthritis Rheumatoid arthritis Sjogren syndrome Systemic lupus erythematosus Type I diabetes

52

High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis  

Microsoft Academic Search

BACKGROUND: Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue and atopic disorders is higher in women with endometriosis than in the general female population. METHODS AND RESULTS: A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members

N. Sinaii; S. D. Cleary; M. L. Ballweg; L. K. Nieman; P. Stratton

2002-01-01

53

Impaired processing of brief, rapidly presented auditory cues in infants with a family history of autoimmune disorder.  

PubMed

Studies have shown that individuals with language disorders, such as developmental dyslexia and specific language impairment, exhibit impairments in the processing of brief, successive, or rapidly changing auditory information. It is also the case that a higher rate of autoimmune disorders have been identified in those with language-based learning disorders and, conversely, that individuals with autoimmune disorders show a higher incidence of language-related disorders. The rapid auditory processing (RAP) deficits described for older individuals with language impairments may also be used as a behavioral marker to identify infants at higher risk for language delays. Thus, we were interested in examining RAP abilities in a subset of infants with a positive family history of autoimmune disorders. Eleven infants from our ongoing prospective longitudinal studies were identified based on parental response to a question about the presence of a family history of autoimmune disease and compared to 11 matched controls. The RAP threshold of each infant was assessed at 6 and 9 months of age using a conditioned head-turn procedure (using tone pairs with brief interstimulus intervals) and an auditory-visual habituation-recognition memory task using computer-generated consonant-vowel syllables (/ba/ vs. /da/). A visual habituation-recognition memory task that did not require processing of brief temporal cues was also administered. Group differences emerged on the infant RAP tasks, and on language outcome measures at 12 and 16 months of age. Infants from families with a history of autoimmune disorder had significantly higher (i.e., poorer) RAP thresholds and lower language scores than did control infants, whereas visual discrimination scores did not differ between family history infants and controls. Moreover, when brief auditory cues were necessary for the discrimination of /ba/ vs. /da/, infants with a family history of autoimmune disorder performed significantly more poorly than did controls. These findings lend support to the hypothesis that a similar mechanism, perhaps a neural-immune interaction, may underlie the observed co-occurrence of autoimmune disorders and learning impairments. PMID:12405509

Benasich, April Ann

2002-01-01

54

Dimethyl Fumarate Protects Pancreatic Islet Cells and Non-Endocrine Tissue in L-Arginine-Induced Chronic Pancreatitis  

PubMed Central

Background Chronic pancreatitis (CP) is a progressive disorder resulting in the destruction and fibrosis of the pancreatic parenchyma which ultimately leads to impairment of the endocrine and exocrine functions. Dimethyl Fumarate (DMF) was recently approved by FDA for treatment of patients with multiple sclerosis. DMF's unique anti-oxidant and anti-inflammatory properties make it an interesting drug to test on other inflammatory conditions. This study was undertaken to determine the effects of DMF on islet cells and non-endocrine tissue in a rodent model of L-Arginine-induced CP. Methods Male Wistar rats fed daily DMF (25 mg/kg) or vehicle by oral gavage were given 5 IP injections of L-Arginine (250 mg/100 g×2, 1 hr apart). Rats were assessed with weights and intra-peritoneal glucose tolerance tests (IPGTT, 2 g/kg). Islets were isolated and assessed for islet mass and viability with flow cytometry. Non-endocrine tissue was assessed for histology, myeloperoxidase (MPO), and lipid peroxidation level (MDA). In vitro assessments included determination of heme oxygenase (HO-1) protein expression by Western blot. Results Weight gain was significantly reduced in untreated CP group at 6 weeks. IPGTT revealed significant impairment in untreated CP group and its restoration with DMF therapy (P <0.05). Untreated CP rats had pancreatic atrophy, severe acinar architectural damage, edema, and fatty infiltration as well as elevated MDA and MPO levels, which were significantly improved by DMF treatment. After islet isolation, the volume of non-endocrine tissue was significantly smaller in untreated CP group. Although islet counts were similar in the two groups, islet viability was significantly reduced in untreated CP group and improved with DMF treatment. In vitro incubation of human pancreatic tissue with DMF significantly increased HO-1 expression. Conclusion Administration of DMF attenuated L-Arginine-induced CP and islet function in rats. DMF treatment could be a possible strategy to improve clinical outcome in patients with CP. PMID:25198679

Robles, Lourdes; Vaziri, Nosratola D.; Li, Shiri; Masuda, Yuichi; Takasu, Chie; Takasu, Mizuki; Vo, Kelly; Farzaneh, Seyed H.; Stamos, Michael J.; Ichii, Hirohito

2014-01-01

55

Antigen and substrate withdrawal in the management of autoimmune thrombotic disorders  

PubMed Central

Prevailing approaches to manage autoimmune thrombotic disorders, such as heparin-induced thrombocytopenia, antiphospholipid syndrome and thrombotic thrombocytopenic purpura, include immunosuppression and systemic anticoagulation, though neither provides optimal outcome for many patients. A different approach is suggested by the concurrence of autoantibodies and their antigenic targets in the absence of clinical disease, such as platelet factor 4 in heparin-induced thrombocytopenia and ?2-glycoprotein-I (?2GPI) in antiphospholipid syndrome. The presence of autoantibodies in the absence of disease suggests that conformational changes or other alterations in endogenous protein autoantigens are required for recognition by pathogenic autoantibodies. In thrombotic thrombocytopenic purpura, the clinical impact of ADAMTS13 deficiency caused by autoantibodies likely depends on the balance between residual antigen, that is, enzyme activity, and demand imposed by local genesis of ultralarge multimers of von Willebrand factor. A corollary of these concepts is that disrupting platelet factor 4 and ?2GPI conformation (or ultralarge multimer of von Willebrand factor oligomerization or function) might provide a disease-targeted approach to prevent thrombosis without systemic anticoagulation or immunosuppression. Validation of this approach requires a deeper understanding of how seemingly normal host proteins become antigenic or undergo changes that increase antibody avidity, and how they can be altered to retain adaptive functions while shedding epitopes prone to elicit harmful autoimmunity. PMID:22966172

McCrae, Keith R.; Zheng, X. Long; Sachais, Bruce S.; Luning Prak, Eline T.; Siegel, Don L.

2012-01-01

56

Comparison of Clinical Characteristics of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections and Childhood Obsessive-Compulsive Disorder  

PubMed Central

Abstract Objective The objectives of this study were to identify unique clinical characteristics of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) compared with a control group of children with non-PANDAS obsessive-compulsive disorder (OCD) with respect to ancillary symptoms, types of obsessions and compulsions, symptom severity, and co-morbid DSM-IV diagnoses. Method Classification of PANDAS was based on review of pediatric and psychiatric records using the criteria developed by Swedo and colleagues. Children aged 6–14 with PANDAS (n?=?21) and non-PANDAS OCD (n?=?18) were assessed by blind independent evaluators using the PANDAS Questionnaire, Children's Yale-Brown Obsessive Compulsive Scale, Yale Global Tic Severity Scale, and Anxiety Disorders Interview Schedule for DSM-IV. Results PANDAS children were significantly more likely to present with separation anxiety, urinary urgency, hyperactivity, impulsivity, deterioration in handwriting, and decline in school performance during their initial episode of neuropsychiatric illness compared with children with OCD. Total tics and vocal tics were more severe in PANDAS children. Separation anxiety disorder and social phobia were more prevalent in non-PANDAS OCD children. Children with non-PANDAS OCD were significantly more likely to include others in their rituals. There were no significant differences between groups on demographics or severity of OCD. Conclusions Distinguishing clinical characteristics in PANDAS, which included urinary urgency, hyperactivity, impulsivity, and deterioration in handwriting, are linked to basal ganglia functions. These clinical characteristics will aid in the differentiation of PANDAS children for research and clinical purposes and ultimately advance our understanding and treatment of this disorder. PMID:20807071

Victor, Andrea M.; Pipal, Allison J.; Williams, Kyle A.

2010-01-01

57

Immunological Profile of HTLV-1-Infected Patients Associated with Infectious or Autoimmune Dermatological Disorders  

PubMed Central

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

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

2013-01-01

58

Assessment of thyroid disorders and autoimmunity in patients with rheumatic diseases.  

PubMed

We investigated whether there was a significant increase in thyroid autoimmunity, and disorders in patients with rheumatic diseases (RDs). We enrolled 201 patients with RDs (41 with ankylosing spondylitis, 15 with systemic lupus erythematosus, 80 with rheumatoid arthritis [RA], 65 with familial Mediterranean fever), and 122 healthy controls. Serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), C-reactive protein, and thyroid autoantibodies (anti-thyroglobulin and anti-thyroid peroxidase) were measured in all participants. There were no significant differences between the ages of the patients and controls. The mean TSH values of the patients with RDs and the controls were 3.1±2.68mIU/L and 1.9±0.83mIU/L, respectively (P = 0.004). The mean fT4 value of the patients with RDs was 1.43±0.67ng/dL whereas that of the controls was 1.58±0.68ng/dL (P <0.001). Subclinical hypothyroidism was detected in 24 patients with RDs. Thyroid antibodies were detected in 16 of 201 (8%) patients with RDs. Three of these patients had subclinical hypothyroidism, while the others were euthyroid. Thyroid autoantibodies were significantly higher in patients with RDs (P <0.001). Additionally, thyroid disorders were observed more frequently in patients with RDs than in the healthy controls. Based on our findings, we recommend that thyroid function tests should better be included in the clinical evaluation of patients with RDs. PMID:24965722

Acay, Akif; Ulu, Memnune Sena; Ahsen, Ahmet; Eroglu, Selma; Ozuguz, Ufuk; Yuksel, Seref; Acarturk, Gursel

2014-01-01

59

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

MedlinePLUS

... Disorder (OCD) (4 Items) Panic Disorder (2 Items) Post-Traumatic Stress Disorder (7 Items) Schizophrenia (2 Items) Social Phobia (2 ... Disorder (OCD) (4 Items) Panic Disorder (2 Items) Post-Traumatic Stress Disorder (7 Items) Schizophrenia (2 Items) Social Phobia (2 ...

60

Treatment of dermatologic connective tissue disease and autoimmune blistering disorders in pregnancy.  

PubMed

Autoimmune skin disease occurs in pregnancy, and treatment is often required to control both maternal disease and fetal outcomes. Here we present the available safety data in pregnancy and lactation for medications used to treat autoimmune skin diseases, including cutaneous lupus erythematosus, dermatomyositis, morphea and systemic sclerosis, pemphigus vulgaris, pemphigus foliaceus, and pemphigoid gestationis. A PubMed search of the English-language literature using keywords, "pregnancy" "rheumatic disease," and "connective tissue disease" was performed. Relevant articles found in the search and references were included. Reasonable evidence supports the careful and cautious use of topical steroids, topical calcineurin inhibitors, systemic corticosteroids, hydroxychloroquine, and azathioprine in pregnancy. Case reports or clinical experience suggest intravenous immunoglobulin, dapsone, phototherapy, rituximab, and plasmapheresis may be safe. Several treatment options exist for autoimmune skin disease in pregnancy and lactation, and should be considered when treating these patients. PMID:23914893

Braunstein, Inbal; Werth, Victoria

2013-01-01

61

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

PubMed Central

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

2013-01-01

62

Biologics-induced autoimmune renal disorders in chronic inflammatory rheumatic diseases: systematic literature review and analysis of a monocentric cohort.  

PubMed

The use of biologic drugs has been linked with the paradoxical development of systemic and organ specific autoimmune processes. The aim of this study was to describe the features of biologics-induced autoimmune renal disorders (AIRD) through a systematic review and a cohort study of 707 adult patients affected with Rheumatoid Arthritis (RA), Ankylosing Spondylitis (SA) and Psoriatic Arthritis (PsA). The literature search identified 2687 articles of which 21 were considered relevant for the present study, accounting for 26 case reports. The cohort analysis retrieved 3 cases. According to clinical manifestations and kidney histology the identified AIRD cases were classified as: a) glomerulonephritis associated with systemic vasculitis (GNSV), b) glomerulonephritis in lupus-like syndrome (GNLS), c) isolated autoimmune renal disorders (IARD). Twenty-two out of 29 cases with AIRD were reported in patients affected by RA, 5 in AS and 2 in PsA. The biologic drug most frequently associated with development of AIRD was Etanercept (15 cases, 51.7%), followed by Adalimumab (9 cases, 31.0%) and Infliximab (3 cases, 10.3%) while Tocilizumab and Abatacept were reported in 1 case (3.4%) for each. Thirteen out of 29 (44.8%) cases were classified as affected by IARD, 12 (41.3%) as GNSV and 4 (13.9%) as GNLS. Worse prognosis was associated with GNSV and lack of biologic withdrawal. Although rare, AIRD may be life-threatening and may lead to renal failure and death. If AIRD occurs, biologic drugs must be stopped and patient should be treated according to clinical manifestations and kidney biopsy findings. PMID:24840285

Piga, Matteo; Chessa, Elisabetta; Ibba, Valentina; Mura, Valentina; Floris, Alberto; Cauli, Alberto; Mathieu, Alessandro

2014-08-01

63

Acute myocardial infarction associated with high dose intravenous immunoglobulin infusion for autoimmune disorders. A study of four cases  

PubMed Central

OBJECTIVE—To report on four patients with autoimmune disorders who developed acute myocardial infarction (MI) during or soon after treatment with high dose intravenous immunoglobulins (IVIG) and to determine the clinical profile of patients prone to this complication.?METHODS—The clinical history of the four patients is reported with details concerning age, sex, indication for IVIG treatment, risk factors, timing of the MI and outcome. The relevant medical literature has been reviewed.?RESULTS—The patients, three men and one woman, aged 42-67, received IVIG treatment for different autoimmune disorders. All had a history of atherosclerosis or previous risk factors such as hypertension, stroke, hyperlipidaemia and obesity. Two of the patients suffered a MI after the first infusion of IVIG while the others—after the 5th and 15th pulses. MI occurred during the infusion in two patients and after a few days in the others. All the patients recovered from the acute event. These observations are in concert with sporadic cases of IVIG related thrombosis reported in the medical literature.?CONCLUSION—In patients with vascular risk factors such as old age, hypertension, history of stroke or coronary artery disease, the possibility of IVIG related vascular complications should be considered and IVIG prescribed with a cautious reweighted risk/benefit consideration.?? PMID:10627434

Elkayam, O.; Paran, D.; Milo, R.; Davidovitz, Y.; Almoznino-Sarafia..., D.; Zeltser, D.; Yaron, M.; Caspi, D.

2000-01-01

64

Cyclooxygenase2 and thromboxane synthase in non-endocrine and endocrine tumors: A review  

Microsoft Academic Search

Prostaglandins (PG) are members of a large group of hormonally active fatty acids derived from free fatty acids. They are\\u000a formed from arachidonic acid—the major PG precursor. Cyclooxygenase (COX)-1 and -2 are the rate-limiting steps in PG synthesis.\\u000a COX-2 is overexpressed in many human non-endocrine and endocrine tumors including colon, breast, prostate, brain, thyroid,\\u000a and pituitary. COX-2 has an important

Onder Onguru; Mary B. Casey; Sabine Kajita; Nobuki Nakamura; Ricardo V. Lloyd

2005-01-01

65

Autoimmune Pancreatitis.  

PubMed

Autoimmune pancreatitis (AIP) is a rare, heterogeneous, fibroinflammatory disorder of the pancreas. It has gained increasing recognition due to a presentation that can mimic difficult to treat disorders such as pancreatic cancer, cholangiocarcinoma and primary sclerosing cholangitis. In contrast, autoimmune pancreatitis is a benign disease that is very responsive to therapy with corticosteroids. There are two types of AIP. Type 1 disease is the most common worldwide and is associated with extrapancreatic manifestations and elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity of IgG4-positive cells, and is more difficult to diagnose. This review provides an update on the diagnosis, pathophysiology and treatment of AIP, with special emphasis on the two subtypes. PMID:24040625

Ketwaroo, Gyanprakash A; Sheth, Sunil

2013-04-01

66

Autoimmune pancreatitis  

PubMed Central

Autoimmune pancreatitis (AIP) is a rare, heterogeneous, fibroinflammatory disorder of the pancreas. It has gained increasing recognition due to a presentation that can mimic difficult-to-treat disorders such as pancreatic cancer, cholangiocarcinoma and primary sclerosing cholangitis. In contrast, autoimmune pancreatitis is a benign disease that is very responsive to therapy with corticosteroids. There are two types of AIP. Type 1 disease is the most common worldwide and is associated with extrapancreatic manifestations and elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity of IgG4-positive cells and is more difficult to diagnose. This review provides an update on the diagnosis, pathophysiology and treatment of AIP, with special emphasis on the two subtypes. PMID:24040625

Ketwaroo, Gyanprakash A.; Sheth, Sunil

2013-01-01

67

Autoimmune pancreatitis.  

PubMed

Autoimmune pancreatitis (AIP) is a rare, heterogeneous, fibroinflammatory disorder of the pancreas. It has gained increasing recognition due to a presentation that can mimic difficult-to-treat disorders such as pancreatic cancer, cholangiocarcinoma and primary sclerosing cholangitis. In contrast, autoimmune pancreatitis is a benign disease that is very responsive to therapy with corticosteroids. There are two types of AIP. Type 1 disease is the most common worldwide and is associated with extrapancreatic manifestations and elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity of IgG4-positive cells and is more difficult to diagnose. This review provides an update on the diagnosis, pathophysiology and treatment of AIP, with special emphasis on the two subtypes. PMID:24759664

Ketwaroo, Gyanprakash A; Sheth, Sunil

2013-07-01

68

On the connection between autoimmunity, tic disorders and obsessive-compulsive disorders: a meta-analysis on anti-streptolysin O titres.  

PubMed

Anti-streptolysin O (ASO) titration is useful in the context of autoimmune pathologies, including specific cases of tic and obsessive-compulsive disorders occurring after streptococcal infections. There is currently a lack of consensus on the use of ASO titres; therefore we performed a meta-analysis to systematise available data and clarify the role of ASO titres in the context of neuropsychiatric disorders. A meta-analysis was performed on ASO titration in neuropsychiatric patients, including tic disorders and obsessive-compulsive disorders. Included studies reported numbers of positive subjects, depending on a chosen threshold, or detailed ASO titrations. Three hundred and twenty nine studies were identified, of which 13 were eligible for meta-analysis. Due to limited available data, only tic disorders were evaluated. The odds ratio of finding an abnormal ASO titre in patients was 3.22 (95% C.I. 1.51-6.88) as compared to healthy controls and 16.14 (95% C.I. 8.11-32.11) as compared to non-psychiatric patients. Studies using different thresholds were generally concordant. ASO titres were also compared quantitatively, finding an overall difference of the means of 70.50 U/ml (95% C.I. 25.21-115.80) in favour of patients with tic disorders. Based on current evidence, tic disorders are associated with a significant increase in ASO titres, evident both in a threshold-level perspective and on a quantitative level. These results encourage the systematisation of ASO titration in the context of tic disorders. PMID:25091468

Pozzi, Marco; Pellegrino, Paolo; Carnovale, Carla; Perrone, Valentina; Antoniazzi, Stefania; Perrotta, Cristiana; Radice, Sonia; Clementi, Emilio

2014-12-01

69

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

PubMed Central

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

Akman-Karaka?, Ay?e; Yalcin, Arzu Didem; Koç, Saliha; Gumuslu, Saadet; ?enol, Ye?im Yi?iter; Özkesici, Birgül; Genc, Gizem Esra; Ergun, Erkan; Ongut, Gozde; Yilmaz, Ertan; Uzun, Soner; Alpsoy, Erkan

2013-01-01

70

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

PubMed Central

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

Levesque, M C

2009-01-01

71

Retroperitoneal disorders associated with IgG4-related autoimmune pancreatitis  

PubMed Central

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

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

2014-01-01

72

Retroperitoneal disorders associated with IgG4-related autoimmune pancreatitis.  

PubMed

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

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

2014-11-28

73

Screening for autoimmune thyroid disorders after spontaneous abortion is cost-saving and it improves the subsequent pregnancy rate  

PubMed Central

Background Hypothyroidism and/or autoimmune thyroid disorders (AITD) may contribute to spontaneous abortions (SpA). Cost-effectiveness analyses of thyroid screening in women after SpA are lacking. Our aim was to evaluate the cost-effectiveness of screening for AITD and/or hypothyroidism and their treatment in women after SpA with regard to their reproductive health. Methods We performed a cross-sectional non-randomized study with follow-up in 2008–2011 in the settings of Departments of Endocrinology and Obstetrics/Gynecology of a university hospital. We enrolled 258 women after SpA before the 12th gestational week and followed them for a median of 3 years. At enrollment, serum concentrations of thyroid stimulatory hormone (TSH), antibodies to thyroid peroxidase (TPOAb) and free thyroxine (FT4) were measured and thyroid ultrasound performed. Women with overt hypothyroidism were treated with levothyroxine (n?=?45; 61.6%) and women with subclinical hypothyroidism or euthyroid AITD were treated (n?=?28; 38.4%) or left untreated (n?=?38; 14.7%). Euthyroid women without signs of AITD served as controls (n?=?147; 57.0%). Results Of the 38 untreated women with AITD and/or subclinical hypothyroidism, 8 (21.1%) reported secondary infertility as compared to 16/147 (10.9%) controls and 3/73 (4.1%) treated women (p?=?0.021). Treatment was associated with an increased rate of successfully completed subsequent pregnancies (increment of 6 newborns/100 women) and a savings of €19,539/100 women. Total costs per successfully completed pregnancy were €1,189 in controls, €1,564 in the treated, and €2,488 in the untreated women. Conclusions Screening for thyroid disorders in women after SpA and treatment with levothyroxine is cost-saving and it improves the subsequent pregnancy rate. PMID:24267864

2013-01-01

74

Autoimmunity in Immunodeficiency  

PubMed Central

Primary immunodeficiencies (PID) comprise a diverse group of clinical disorders with varied genetic defects. Paradoxically, a substantial proportion of PID patients develop autoimmune phenomena in addition to having increased susceptibility to infections from their impaired immunity. Although much of our understanding comes from data gathered through experimental models, there are several well-characterized PID that have improved our knowledge of the pathways that drive autoimmunity. The goals of this review will be to discuss these immunodeficiencies and to review the literature with respect to the proposed mechanisms for autoimmunity within each put forth to date. PMID:23591608

Todoric, Krista; Koontz, Jessica B.; Mattox, Daniel; Tarrant, Teresa K.

2013-01-01

75

Antithyroglobulin monoclonal and autoantibodies cross-react with an orbital connective tissue membrane antigen: a possible mechanism for the association of ophthalmopathy with autoimmune thyroid disorders.  

PubMed Central

The possibility that Graves' ophthalmopathy and autoimmune thyroid disorders may be associated because of autoimmune reactions against antigens shared between human orbital and thyroid tissues was investigated using anti-thyroglobulin (Tg) monoclonal and autoantibodies. Eleven of 16 mouse monoclonal antibodies (MCAB) tested reacted, in an enzyme-linked immunosorbent assay (ELISA), with an antigen in human orbital connective tissue membranes (OCTmem), but not with the OCT soluble fraction, or with membrane or soluble fractions of human eye muscle, lacrimal gland or skin connective tissue. The anti-OCTmem activity was absorbed by OCTmem and Tg, but not by liver membranes or bovine serum albumin (BSA). In preliminary studies four out of 113 human MCAB against thyroid or orbital tissue antigens showed reactivity restricted to Tg and OCTmem. Sera from approximately 50% of patients with autoimmune thyroid disorders, with or without ophthalmopathy, also reacted with OCTmem. The autoantibody activity correlated closely with serum titres of antithyroglobulin but not with the presence, duration, or severity of the eye disease. The OCTmem reactivity was absorbed by Tg, thyroid membranes, and OCTmem but not liver membranes, membranes prepared from other orbital tissues, or BSA. The OCTmem-Tg shared antigen site appeared not to be native thyroglobulin since, (i) MCAB and serum autoantibodies did not react with the cytosol fraction of OCT, and (ii) because the membrane antigen was not solubilizable. Because not all patients with ophthalmopathy have detectable anti-Tg antibodies and, conversely, because not all patients with detectable anti-Tg antibodies develop ophthalmopathy it is unlikely that autoimmunity against a OCTmem-Tg shared antigen is the primary mechanism of Graves' ophthalmopathy, although this possibility has not been excluded. On the other hand the reaction of anti-Tg autoantibodies with OCT membranes may be a model for other autoimmune reactions against other thyroid-orbital tissue-shared antigens. While the pathogenesis of Graves' ophthalmopathy is likely to be multifactorial, humoral and cellular reactions against primary orbital antigens, thyroid-orbitol tissue shared antigens, or both, are likely to play important roles. PMID:3841305

Kuroki, T; Ruf, J; Whelan, L; Miller, A; Wall, J R

1985-01-01

76

High prevalence of latent tuberculosis infection in autoimmune disorders such as psoriasis and in chronic respiratory diseases, including lung cancer.  

PubMed

The early diagnosis and treatment of individuals harboring M. tuberculosis is key to ensuring the effectiveness of health programs aimed at the elimination of tuberculosis (TB). Monitoring for TB also has other important health care implications for the related immune pathology caused by the chronic inflammatory response to M. tuberculosis. Moreover, the recent introduction of biologic therapies for the treatment of several immune-mediated inflammatory diseases has shown unexpected high frequencies of reactivation of latent TB. The present cross-sectional study is aimed at estimating the prevalence of latent tuberculosis infection (LTBI) in different groups of subjects, either undergoing a routine program of screening for TB or a clinical monitoring of autoimmune or lung disorders, by analyzing their immune response in vitro to a pool of different M. tuberculosis antigens through an IFN-gamma-release assay (IGRA). We consecutively tested 1,644 subjects including health care workers (931), healthy immigrants from different countries (93), patients with a diagnosis of psoriasis (405), patients with lung inflammatory disease (60) or lung neoplasia (32) and a group of HIV-1 infected Italian subjects (120). The prevalence of IGRAs positive responses among health care workers was 8.9 percent. In comparison, significantly higher frequencies were found in healthy immigrant subjects (33.3%), similar to those found in inflammatory broncho-pneumopathies (34.5%) or lung cancer (29.6%). Interestingly, an unexpected high prevalence was also found in patients affected by psoriasis (18.0%), while HIV-infected subjects had values comparable to those of health care workers (10.8%). An age cut-off was determined and applied for each group by receiver operating characteristic (ROC) curves in order to perform the statistical analysis among age-comparable groups. Multivariate analysis showed that the age and clinical conditions such as having a diagnosis of psoriasis or a lung inflammatory disease were independent risk factors for developing an IGRA positive response. This study highlights an unprecedented high prevalence of IGRA positive responses among patients affected by psoriasis and emphasizes the need for a preliminary assessment of LTBI before the administration of any biologic therapy based on cytokine antagonists such as anti-TNF-alpha. Moreover, screening for LTBI should be routinely performed in the presence of a chronic pulmonary disease. PMID:21880210

Bordignon, V; Bultrini, S; Prignano, G; Sperduti, I; Piperno, G; Bonifati, C; Filippetti, M; Toma, L; Latini, A; Di Cecio, M; Giuliani, A; Vocaturo, A; Trento, E; D' Agosto, G; Francesconi, F; Cataldo, A; Vento, A; Cilenti, V; Berardesca, E; Ameglio, F; Cordiali Fei, P; Ensoli, F

2011-01-01

77

Autoimmune autonomic ganglionopathy.  

PubMed

Autoimmune autonomic ganglionopathy is an idiopathic acquired disorder of the autonomic nervous system associated with antibodies to the ganglionic nicotinic acetylcholine receptor found in sympathetic, parasympathetic and enteric ganglia. Symptoms and signs reflect diffuse impairment of autonomic functions. Prominent features are gastrointestinal dysmotility, orthostatic hypotension, and tonic pupils. Typical cases have a subacute onset (less than 3 months to maximum symptoms), are monophasic, and may show partial improvement over the course of several months. Other cases have a slowly progressive course which can resemble degenerative forms of autonomic failure. Treatment for milder cases is supportive care for symptom management. Anecdotally, plasma exchange, intravenous immunoglobulin, corticosteroids or immunosuppression have been used successfully to treat more severe cases. Autoimmune autonomic ganglionopathy represents one of a small group of autoimmune neuromuscular disorders that are caused by antibodies against ion channels. PMID:19349706

Winston, Nicole; Vernino, Steven

2009-01-01

78

Living with the unexplained: coping, distress, and depression among women with chronic fatigue syndrome and/or fibromyalgia compared to an autoimmune disorder.  

PubMed

Chronic fatigue syndrome (CFS) and fibromyalgia are disabling conditions without objective diagnostic tests, clear-cut treatments, or established etiologies. Those with the disorders are viewed suspiciously, and claims of malingering are common, thus promoting further distress. It was hypothesized in the current study that levels of unsupportive social interactions and the coping styles used among those with CFS/fibromyalgia would be associated with perceived distress and depressive symptoms. Women with CFS/fibromyalgia (n=39), in fact, reported higher depression scores, greater perceived distress and more frequent unsupportive relationships than healthy women (n=55), whereas those with a chronic, but medically accepted illness comprising an autoimmune disorder (lupus erythematosus, multiple sclerosis, rheumatoid arthritis; n=28), displayed intermediate scores. High problem-focused coping was associated with low levels of depression and perceived distress in those with an autoimmune condition. In contrast, although CFS/fibromyalgia was also accompanied by higher depression scores and higher perceived distress, this occurred irrespective of problem-focused coping. It is suggested that because the veracity of ambiguous illnesses is often questioned, this might represent a potent stressor in women with such illnesses, and even coping methods typically thought to be useful in other conditions, are not associated with diminished distress among those with CFS/fibromyalgia. PMID:24479644

McInnis, Opal A; Matheson, Kimberly; Anisman, Hymie

2014-01-01

79

Autoimmune Autonomic Ganglionopathy  

Microsoft Academic Search

Autoimmune autonomic ganglionopathy is an idiopathic acquired disorder of the autonomic nervous system associated with antibodies to the ganglionic nicotinic acetylcholine receptor found in sympathetic, parasympathetic and enteric ganglia. Symptoms and signs reflect diffuse impairment of autonomic functions. Prominent features are gastrointestinal dysmotility, orthostatic hypotension, and tonic pupils. Typical cases have a subacute onset (less than 3 months to maximum

Nicole Winston; Steven Vernino

2009-01-01

80

Multiple Autoimmune Syndromes Associated with Psoriasis: A Rare Clinical Presentation  

PubMed Central

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. PMID:24715941

Masood, Sadia; Sajid, Sara; Jafferani, Asif; Tabassum, Saadia; Ansar, Sobia

2014-01-01

81

Autoimmune and paraneoplastic channelopathies.  

PubMed

Thirty years ago, antibodies against the muscle acetylcholine receptor (AChR) were recognized as the cause of myasthenia gravis. Since then, there has been great interest in identifying other neurological disorders associated with autoantibodies. Several other antibody-mediated neuromuscular disorders have been identified, each associated with an antibody against a ligand- or voltage-gated ion channel. The Lambert-Eaton syndrome is caused by antibodies against voltage-gated calcium channels and often occurs in patients with small cell lung cancer. Acquired neuromyotonia is caused by voltage-gated potassium channel antibodies, and autoimmune autonomic ganglionopathy is caused by antibodies against the neuronal AChR in autonomic ganglia. There is good evidence that antibodies in these disorders cause changes in synaptic function or neuronal excitability by directly inhibiting ion channel function. More recently, studies have identified ion channel antibodies in patients with certain CNS disorders, such as steroid-responsive encephalitis and paraneoplastic cerebellar ataxia. It remains unclear if antibodies can gain access to the CNS and directly cause ion channel dysfunction. Treatment of autoimmune channelopathies includes drugs that help restore normal neuronal function and treatments to remove pathogenic antibodies (plasma exchange) or modulate the immune response (steroids or immunosuppressants). These disabling neurological disorders may be dramatically responsive to immunomodulatory therapy. Future studies will likely lead to identification of other ion channel antibodies and other autoimmune channelopathies. PMID:17395141

Vernino, Steven

2007-04-01

82

Cellular Targeting in Autoimmunity  

PubMed Central

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

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

2012-01-01

83

Accidental fall due to abnormal behavior after experiencing a Streptococcus pyogenes infection: febrile delirium or pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection?  

PubMed

An 11-year-old boy with a high fever (39.4 degrees C) presented at a local medical institution. His condition was diagnosed as hemolytic streptococcal infection, and he was prescribed an antibiotic. After returning home, he took a dose of his medication and rested; however, he suddenly began to run around while yelling incomprehensible words. He ran up to his room on the second floor and fell from the second floor window down to the ground. He lost consciousness and was transferred to our department. His history included being born as a twin with a low birth weight and pneumonia at 1 year of age. He regained consciousness on the seventh hospital day and was discharged without any neurological abnormality on the 14th day. His abnormal behavior might have resulted from febrile delirium or an unusual expression of pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection. PMID:19687712

Yanagawa, Youichi; Kaneko, Naoyuki; Higashidate, Seiki; Matsumoto, Hiroshi

2009-08-01

84

Recalcitrant hypocalcaemia in autoimmune enteropathy.  

PubMed

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome is a monogenic disorder associated with autoimmune destruction of both endocrine and nonendocrine tissues. The classic triad includes candidiasis, hypoparathyroidism, and Addison disease. Up to 25% of patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome also have gastrointestinal manifestations, which can have an impact on the management of other aspects of the disease. The management of the case discussed was challenging because of the complex interplay between the manifestations and treatment of his hypoparathyroidism, Addison disease, and autoimmune enteropathy. Attempts at management of hypocalcemia were largely unsuccessful until the introduction of immunosuppressive therapy for autoimmune enteropathy. This case supports early consideration of immunosuppression in this condition. PMID:25404718

Geyer, Myfanwy; Fairchild, Jan; Moore, David; Moore, Lynette; Henning, Paul; Tham, Elaine

2014-12-01

85

Rheumatic symptoms in autoimmune thyroiditis.  

PubMed

Autoimmune thyroiditis (ATD) is generally regarded as a classic example of single organ autoimmunity with a high association with endocrine thyroid disorders. However, it is closely associated with several autoimmune diseases including rheumatologic syndromes and has long been known to have several rheumatic manifestations particularly in association with hypothyroidism. More recently, it has also been implicated in rheumatologic syndromes in the absence of hypothyroidism or subclinical hypothyroidism. There is also an emerging body of evidence that ATD is highly linked to chronic generalized pain syndromes including fibromyalgia. This review examines the rheumatic symptoms of ATD described in the current literature and discusses the clinical relevance of ATD in general rheumatology. PMID:25618571

Tagoe, Clement E

2015-02-01

86

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

PubMed

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

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

2015-01-15

87

Endocrine autoimmunity in Turner syndrome  

PubMed Central

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. PMID:24355069

2013-01-01

88

The autoimmune diseases  

SciTech Connect

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.

1985-01-01

89

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

PubMed

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

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

2014-05-30

90

Concise review: engineering the fusion of cytokines for the modulation of immune cellular responses in cancer and autoimmune disorders.  

PubMed

As our understanding of the basic precepts of immunobiology continue to advance at a rapid pace, translating such discoveries into meaningful therapies for patients has proved challenging. This is especially apparent in the use of cytokine-based immunotherapies for cancer. Unanticipated and serious side effects, as well as low objective response rates seen in clinical trials, have dealt setbacks to the field. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and common ?-chain (?-c) interleukins are cytokines that have been used as stand-alone immunotherapies with moderate success. Our group has found that the fusion of GM-CSF to members of ?-c interleukins results in the generation of novel proteins with unique signaling properties and unheralded biological effects. These fusion proteins, termed GIFT (GM-CSF interleukin fusion transgenes) fusokines, are the result of combining GM-CSF and a ?-c interleukin into a single, bifunctional polypeptide. In our experience, GIFT fusokines often confer immune cells with a gain of function that cannot be explained by the mere sum of their constituent moieties. They act as bispecific ligands, coupling activated GM-CSF and interleukin receptors together to drive unique downstream signaling events. The synergy that arises from these fusions has shown great promise in its ability to modulate the immune response and overcome maladaptive biological processes that underlie diseases such as cancer and autoimmune conditions. In this review, we discuss the ways in which the GIFT fusokines are able to alter the immune response, particularly in disease states, with a special emphasis on how these novel molecules may be translated into effective therapies in the clinical setting. PMID:25391644

Ng, Spencer; Galipeau, Jacques

2015-01-01

91

Differential Mucosal IL-17 Expression in Two Gliadin-Induced Disorders: Gluten Sensitivity and the Autoimmune Enteropathy Celiac Disease  

PubMed Central

Background The immune-mediated enteropathy, celiac disease (CD), and gluten sensitivity (GS) are two distinct clinical conditions that are both triggered by the ingestion of wheat gliadin. CD, but not GS, is associated with and possibly mediated by an autoimmune process. Recent studies show that gliadin may induce the activation of IL-17-producing T cells and that IL-17 expression in the CD mucosa correlates with gluten intake. Methods The small-intestinal mucosa of patients with CD and GS and dyspeptic controls was analyzed for expression of IL-17A mRNA by quantitative RT-PCR. The number of CD3+ and TCR-?? lymphocytes and the proportion of CD3+ cells coexpressing the Th17 marker CCR6 were examined by in situ small-intestinal immunohistochemistry. Results Mucosal expression of IL-17A was significantly increased in CD but not in GS patients, compared to controls. This difference was due to enhanced IL-17A levels in >50% of CD patients, with the remainder expressing levels similar to GS patients or controls, and was paralleled by a trend toward increased proportions of CD3+CCR6+ cells in intestinal mucosal specimens from these subjects. Conclusion We conclude that GS, albeit gluten-induced, is different from CD not only with respect to the genetic makeup and clinical and functional parameters, but also with respect to the nature of the immune response. Our findings also suggest that two subgroups of CD, IL-17-dependent and IL-17-independent, may be identified based on differential mucosal expression of this cytokine. PMID:19940509

Sapone, Anna; Lammers, Karen M.; Mazzarella, Giuseppe; Mikhailenko, Irina; Carteně, Maria; Casolaro, Vincenzo; Fasano, Alessio

2010-01-01

92

Skin Involvement in Systemic Autoimmune Diseases  

Microsoft Academic Search

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

2008-01-01

93

[Autoimmune hemolytic anemia].  

PubMed

Diagnosis of autoimmune hemolytic anemia (AIHA) requires both serologic evidence of an autoantibody and hemolysis. Based on the characteristic temperature reactivity of the autoantibody to red cell membranes, AIHA is classified into warm AIHA or cold AIHA (cold agglutinin disease and paroxysmal cold hemoglobinuria). Sensitized RBCs are destructed by intravascular and/or extravascular hemolysis. On the basis of etiology, AIHA are classified as idiopathic or secondary. The common cause of secondary AIHA is lymphoproliferative disorders, autoimmune diseases, and infections. The first line therapy of patients with warm AIHA is glucocorticoids and primary treatment for cold AIHA is avoiding cold exposure. The other standard treatments include splenectomy and immunosuppressive drugs. Recently, rituximab, a monoclonal anti-CD20 antibody, has been used in refractory AIHA with excellent responses. PMID:18326320

Karasawa, Masamitsu

2008-03-01

94

A case control study on psychiatric disorders in Hashimoto disease and euthyroid goitre: not only depressive but also anxiety disorders are associated with thyroid autoimmunity  

Microsoft Academic Search

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

2005-01-01

95

Polyglandular autoimmune syndrome: current concepts.  

PubMed Central

The polyglandular autoimmune syndrome (PGAS) is characterized by the association of two or more endocrine disorders that are mediated by autoimmune mechanisms and usually lead to a hypofunctional state. In this review we classify the various types of PGAS and discuss their clinical features and the pathophysiologic autoimmune mechanisms that are thought to play an important role. Circulating organ- and cell-specific autoantibodies are frequently detected in patients with the syndrome and may be a marker of future organ failure. PGAS should be considered in patients with one or more of the disorders constituting the syndrome; this should facilitate early diagnosis and perhaps even prevention of other components of the disease. Early recognition and replacement therapy can be life-saving, particularly when there is adrenal or thyroid insufficiency. PMID:3281737

Meyerson, J; Lechuga-Gomez, E E; Bigazzi, P E; Walfish, P G

1988-01-01

96

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

PubMed Central

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

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

2010-01-01

97

[Autoimmune thrombophilia].  

PubMed

Antibodies against phospholipids and phospholipid-binding proteins, especially anti-cardiolipin and anti-beta2-glycoprotein I antibodies, are important diagnostic markers of autoimmune thrombophilia. These autoantibodies are quite common among patients with systemic lupus erythematosus but can also be found in individuals without concurrent rheumatic conditions. Apart from thromboembolic disease, these antibodies are linked to recurring fetal loss and intrauterine fetal death. In patients with recurring thrombotic events in whom anti-phospholipid antibodies or prolonged aPTT (as a sign of lupus anticoagulant activity) is found, long-term or even lifelong anticoagulation therapy should be considered. Habitual spontaneous abortions and other obstetric complications are often preventable with LMW heparin in combination with low-dose acetylsalicylic acid. In this review, we outline a diagnostic strategy for uncovering autoimmune thrombophilia supplemented with functional and genetic tests for hypercoagulability. PMID:16109186

Heegaard, Niels H H; Locht, Henning

2005-08-01

98

Immunotherapy for autoimmune autonomic ganglionopathy  

Microsoft Academic Search

Purpose of reviewTo provide an update on recent advances in the treatment of autoimmune autonomic ganglionopathy (AAG). AAG is an immune-mediated disorder characterized by prominent and selective involvement of autonomic nerve fibers or ganglia. Treatment with intravenous immunoglobulin (IVIG) or plasma exchange (PE) has been reported to be effective in single case reports and recent case series. This review summarizes

Valeria Iodice; Kurt Kimpinski; Steven Vernino; Paola Sandroni; Phillip A. Low

2009-01-01

99

Clinical Indications and Biological Mechanisms of Splenic Irradiation in Autoimmune Diseases  

Microsoft Academic Search

Background: Splenic irradiation (SI) is a fairly unknown treatment modality in autoimmune disorders like autoimmune thrombocytopenia (AIT) or autoimmune hemolytic anemia (AIHA), which may provide an effective, low toxic and cost-effective treatment for selected patients. Patients, Materials and Methods: This article reviews the limited experiences on splenic irradiation in autoimmune thrombocytopenia by analyzing the current studies including 71 patients and

Martin Weinmann; Gerd Becker; Hermann Einsele; Michael Bamberg

2001-01-01

100

Hepatitis C virus infection and autoimmune diseases  

PubMed Central

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. PMID:23118549

Paroli, Marino; Iannucci, Gino; Accapezzato, Daniele

2012-01-01

101

Autoimmune Epilepsy  

PubMed Central

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. PMID:22451162

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.

2013-01-01

102

[Autoimmune autonomic ganglionopathy].  

PubMed

Autoimmune autonomic ganglionopathy (AAG) is a disorder of isolated autonomic failure associated with antibodies to the nitotinic acetylcholine receptor of the autonomic ganglia resulting in severe autonomic dysfunction. The disorder is associated with and most likely caused by antibodies to gAChR. In this study, we attempted to develop a novel technique to detect antibodies that bind to gAChR. We established a simple in vitro system termed GLIP (gaussia luciferase-reporter immunoprecipitation), which can detect protein-protein interactions with high sensitivity and using no radioisotope. Using this new method, we extensively reviewed the case histories with current clinical and laboratory evaluations that include testing for antibodies to p3 and 34 subunits of gAChR in serum available from the time of symptom onset. Here, we describe 7 patients with gAChR autoantibody and autonomic dysfunction. Our observations also suggest that autoimmune-mediated impairment of autonomic function may be partially reversible. Six of 7 patients improved in response to immunotherapy (e.g. PP, IVMP, IVIg, and immunosuppressant drugs) with symptomatic therapy. We interpreted the improvement in clinical symptoms correlated with the decrease in the levels of anti gAChR antibodies in each case. Some patients with seropositive AAG respond to treatment with IVMP or PP or IVIg, although when used as a single agent, subsequent treatments are required in patients to maintain the improvement. PMID:24291882

Nakane, Shunya

2013-01-01

103

Autoimmune autonomic ganglionopathy  

PubMed Central

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. PMID:17536048

Wang, Z.; Low, P.A.; Jordan, J.; Freeman, R.; Gibbons, C.H.; Schroeder, C.; Sandroni, P.; Vernino, S.

2008-01-01

104

Skin involvement in systemic autoimmune diseases.  

PubMed

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, Henoch-Schönlein purpura, cryoglobulinemic vasculitis, Behcet disease, Wegener granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome range from papules, subcutaneous nodules and livedo reticularis, to palpable purpura, hemorrhagic bulla and ulcerating lesions. Pathological skin manifestations in autoimmune endocrinopathies include pretibial myxedema/dermopathy in Graves' disease, diabetic dermopathy and necrobiosis lipoidica in type I autoimmune diabetes mellitus, candidiasis, ectodermal dysplasia, vitiligo and alopecia areata in APECED and uniform hyperpigmentation of the skin in Addison's disease. Autoimmune gastrointestinal disorders such as inflammatory bowel disease (with erythema nodosum), gluten-sensitive enteropathy (with dermatitis herpetiformis), autoimmune hepatitis and primary biliary cirrhosis (with jaundice and pruritus), hematologic/oncologic disorders such as acute and chronic graft-versus-host disease (with skin manifestations ranging from pruritic maculopapular eruptions and lichen planus-like lesions to generalized scleroderma), and paraneoplastic autoimmune dermatoses are discussed as well. PMID:18460895

Rashtak, Shadi; Pittelkow, Mark R

2008-01-01

105

Free radical theory of autoimmunity  

PubMed Central

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

Kannan, Subburaj

2006-01-01

106

Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease  

Microsoft Academic Search

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

2003-01-01

107

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

PubMed

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

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

2003-09-01

108

Amplification of autoimmune disease by infection  

PubMed Central

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

Posnett, David N; Yarilin, Dmitry

2005-01-01

109

Autoimmune Cytopenias In Common Variable Immunodeficiency  

PubMed Central

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

Podjasek, Jenna C.; Abraham, Roshini S.

2012-01-01

110

The role of AIRE in human autoimmune disease  

Microsoft Academic Search

The autoimmune regulator (AIRE) gene encodes a transcription factor involved in the presentation of tissue-restricted antigens during T-cell development in the thymus. Mutations of this gene lead to type 1 autoimmune polyglandular syndrome (APS-1), also termed autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, which is characterized by the clinical presentation of at least two of a triad of underlying disorders: Addison disease,

Eitan M. Akirav; Nancy H. Ruddle; Kevan C. Herold

2010-01-01

111

Neurocognitive Function in Systemic Autoimmune and Rheumatic Diseases  

Microsoft Academic Search

\\u000a An autoimmune disease is a disorder in which the body’s immune system attacks itself. The dysregulation of the immune system\\u000a associated with systemic autoimmune diseases can affect various organs systems, including the brain. This chapter will review\\u000a the neuropsychological involvement and the resulting cognitive changes associated with three systemic autoimmune or rheumatic\\u000a diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA),

Amy H. Kao; Carol M. Greco; Suzanne L. Gharib; Sue R. Beers

112

Leaky gut and autoimmune diseases.  

PubMed

Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiologic modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the zonulin pathway is deregulated in genetically susceptible individuals, autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing the zonulin-dependent intestinal barrier function. Both animal models and recent clinical evidence support this new paradigm and provide the rationale for innovative approaches to prevent and treat autoimmune diseases. PMID:22109896

Fasano, Alessio

2012-02-01

113

Analysis of the Fc Receptor-Like-3 (FCRL3) Locus in Caucasians with Autoimmune Disorders Suggests a Complex Pattern of Disease Association  

Microsoft Academic Search

Context: A four-marker haplotype in the 5 region of the Fc receptor- like 3 gene (markers FCRL3_3 to FCRL3_6) has been identified re- cently as contributing to rheumatoid arthritis (RA) susceptibility in the Japanese population. The promoter FCRL3_3*C allele also showed significant association with autoimmune thyroid disease and systemic lupus erythematosus. These findings raise the possibility that this locus may

Catherine J. Owen; Hannah Kelly; James A. Eden; Marilyn E. Merriman; Simon H. S. Pearce; Tony R. Merriman

114

Perspectives on autoimmunity  

SciTech Connect

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.

Cohen, I.R.

1987-01-01

115

Autoimmune polyglandular syndromes  

Microsoft Academic Search

The autoimmune polyglandular syndromes—a group of syndromes comprising a combination of endocrine and nonendocrine autoimmune diseases—differ in their component diseases and in the immunologic features of their pathogenesis. One of the three main syndromes, type 1 autoimmune polyglandular syndrome (APS-1), has a unique pathogenic mechanism owing to mutations in the autoimmune regulator (AIRE) gene, which results in the loss of

Peter A. Gottlieb; Aaron W. Michels

2010-01-01

116

Primer: epigenetics of autoimmunity  

Microsoft Academic Search

Interactions between environmental and genetic factors are proposed to explain why autoimmunity afflicts certain individuals and not others. Genes and genetic loci predisposing to autoimmunity are being identified, but theories as to how the environment contributes to autoimmunity still rely largely on examples such as drug-induced systemic lupus erythematosus (SLE) and epidemiologic evidence of occupational exposure, without clear mechanistic explanations

Bruce Richardson

2007-01-01

117

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy from the pediatric perspective.  

PubMed

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

2013-11-01

118

Helicobacter pylori and autoimmune disease: Cause or bystander  

PubMed Central

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

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

2014-01-01

119

Helicobacter pylori and autoimmune disease: cause or bystander.  

PubMed

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

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

2014-01-21

120

Bitter correlationship between autoimmune hepatitis and smoking.  

PubMed

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

Bose, Tanima

2015-02-01

121

Autoimmune Cytopenias in Chronic Lymphocytic Leukemia  

PubMed Central

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; Musto, Pellegrino

2013-01-01

122

Toward defining the autoimmune microbiome for type 1 diabetes  

Microsoft Academic Search

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

Adriana Giongo; Kelsey A Gano; David B Crabb; Nabanita Mukherjee; Luis L Novelo; George Casella; Jennifer C Drew; Jorma Ilonen; Mikael Knip; Heikki Hyöty; Riitta Veijola; Tuula Simell; Olli Simell; Josef Neu; Clive H Wasserfall; Desmond Schatz; Mark A Atkinson; Eric W Triplett

2011-01-01

123

Polymyositis, dermatomyositis, and autoimmune necrotizing myopathy: clinical features.  

PubMed

Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders predominantly affecting skeletal muscles, resulting in muscle inflammation and weakness. The 3 most common inflammatory myopathies are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. This review details the clinical findings noted in PM, DM, and the emerging entity of autoimmune necrotizing myopathy. PMID:21444016

Khan, Sabiha; Christopher-Stine, Lisa

2011-05-01

124

Pituitary autoimmunity: 30 years later  

PubMed Central

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-secreting 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.

2012-01-01

125

Neuronal acetylcholine receptor autoimmunity.  

PubMed

Nicotinic acetylcholine receptors (AChRs) are ligand-gated cation channels that are present throughout the nervous system. The muscle AChR mediates transmission at the neuromuscular junction; antibodies against the muscle AChR are the cause of myasthenia gravis. There are numerous subtypes of AChRs present throughout the nervous system. These neuronal AChRs are closely related to the muscle AChR structurally, but are pharmacologically and immunologically distinct. The ganglionic (alpha3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic, and enteric autonomic ganglia. Ganglionic AChR antibodies are found in up to 50% of patients with autoimmune autonomic ganglionopathy (AAG). Patients with AAG present with severe autonomic failure. Major clinical features include orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, bladder dysfunction, and sicca symptoms. Impaired pupillary light reflex is often seen. Like myasthenia, AAG is an antibody-mediated neurological disorder. Patients may improve with plasma exchange treatment or other immunomodulatory treatment. Experimental AAG, which recapitulates many of the features of the human disease, can be induced in rabbits by immunization against the ganglionic AChR or by passive transfer of antibodies to mice. Ganglionic AChR IgG inhibits nicotinic membrane current in cultured neuroblastoma cells. Central nervous system neuronal AChRs may also be targets of autoimmunity. For example, antibodies against alpha7-type AChRs have been identified in a few patients with encephalitis. It is still unclear if antibodies against receptors in the central nervous system can directly cause disease. PMID:18567861

Vernino, Steven

2008-01-01

126

Chronic Granulomatous Disease as a Risk Factor for Autoimmune Disease  

PubMed Central

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. PMID:18823651

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.

2009-01-01

127

Sirolimus for Autoimmune Disease of Blood Cells  

ClinicalTrials.gov

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

2014-10-17

128

Using T-Cells for Transplantation and Autoimmune Therapy  

Cancer.gov

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 often not effective, and is typically associated with significant side effects, including global immune suppression. Researchers at NCI's Experimental Transplantation and Immunology Branch have developed a cellular therapy to treat graft-vs.-host disease (GVHD) that results from hematopoetic transplant and other autoimmune disorders.

129

Metals and kidney autoimmunity.  

PubMed Central

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

Bigazzi, P E

1999-01-01

130

Autoimmunity: Alopecia Areata  

Microsoft Academic Search

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

2004-01-01

131

Autoimmune lymphoproliferative syndrome.  

PubMed

Autoimmune lymphoproliferative syndrome arises early in childhood in people who inherit mutations in genes that mediate lymphocyte apoptosis, or programmed cell death. In the immune system, antigen-induced lymphocyte apoptosis maintains immune homeostasis by limiting lymphocyte accumulation and minimizing reactions against self-antigens. In autoimmune lymphoproliferative syndrome, defective lymphocyte apoptosis manifests as chronic, nonmalignant adenopathy and splenomegaly; the expansion of an unusual population of CD4-CD8- T cells; and the development of autoimmune disease. Most cases of autoimmune lymphoproliferative syndrome involve heterozygous mutations in the lymphocyte surface protein Fas (CD95, Apo1) that impair a major apoptotic pathway. Prospective evaluations of patients and their families have revealed an ever-expanding spectrum of autoimmune lymphoproliferative syndrome and its major complications. PMID:12819469

Sneller, Michael C; Dale, Janet K; Straus, Stephen E

2003-07-01

132

Autoimmune Cholangitis: A Variant Syndrome of Autoimmune Hepatitis  

PubMed Central

Autoimmune cholangitis (AIC) or autoimmune cholangiopathy is a chronic inflammation of liver and a variant syndrome of autoimmune hepatitis (AIH). We present a case of an adult female who had biochemical features of cholestasis and transaminasemia but aminotransferases were not in the hepatitis range and had histological evidence of bile duct injury which was subsequently diagnosed as autoimmune cholangitis. PMID:25374727

Sharma, Brij; Raina, Sujeet; Sharma, Rajesh

2014-01-01

133

Molecular Diagnosis in Autoimmune Skin Blistering Conditions  

PubMed Central

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

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

2014-01-01

134

Evaluation of Basal Ganglia and Thalamic Inflammation in Children With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infection and Tourette Syndrome: A Positron Emission Tomographic (PET) Study Using 11C-[R]-PK11195.  

PubMed

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

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

2014-08-12

135

Scurfy mice: A model for autoimmune disease  

SciTech Connect

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.

Godfrey, V.L.

1993-01-01

136

Nanomedicine in autoimmunity.  

PubMed

The application of nanotechnology to the diagnosis and therapy of human diseases is already a reality and is causing a real revolution in how we design new therapies and vaccines. In this review we focus on the applications of nanotechnology in the field of autoimmunity. First, we review scenarios in which iron oxide nanoparticles have been used in the diagnosis of autoimmune diseases, mostly through magnetic resonance imaging (MRI), both in animal models and patients. Second, we discuss the potential of nanoparticles as an immunotherapeutic platform for autoimmune diseases, for now exclusively in pre-clinical models. Finally, we discuss the potential of this field to generate the 'perfect drug' with the capacity to report on its therapeutic efficacy in real time, that is, the birth of theranostics in autoimmunity. PMID:24406504

Clemente-Casares, Xavier; Santamaria, Pere

2014-01-01

137

Immune aging and autoimmunity  

PubMed Central

Age is an important risk for autoimmunity, and many autoimmune diseases preferentially occur in the second half of adulthood when immune competence has declined and thymic T cell generation has ceased. Many tolerance checkpoints have to fail for an autoimmune disease to develop, and several of those are susceptible to the immune aging process. Homeostatic T cell proliferation which is mainly responsible for T cell replenishment during adulthood can lead to the selection of T cells with increased affinity to self- or neoantigens and enhanced growth and survival properties. These cells can acquire a memory-like phenotype, in particular under lymphopenic conditions. Accumulation of end-differentiated effector T cells, either specific for self-antigen or for latent viruses, have a low activation threshold due to the expression of signaling and regulatory molecules and generate an inflammatory environment with their ability to be cytotoxic and to produce excessive amounts of cytokines and thereby inducing or amplifying autoimmune responses. PMID:22466672

Weyand, Cornelia M.

2014-01-01

138

Autoimmune diseases and venous thromboembolism: a review of the literature  

PubMed Central

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

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

2012-01-01

139

[Necrotizing autoimmune myopathy].  

PubMed

Idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by symmetrical proximal muscle weakness. One of them is the subgroup of necrotizing autoimmune myopathy, which has recently been recognized as a separate entity. In addition to the typical symmetrical muscle weakness, it is characterized by very high creatine kinase levels, myopathic triad in the electromyography, and myocyte necrosis without significant inflammation. The paper aims to review this rare entity, which has to be diagnosed and treated quickly in every case. PMID:22985665

Bodoki, Levente; Vincze, Melinda; Hortobágyi, Tibor; Griger, Zoltán; Cseri, Karolina; Sz?ll?si, Lászlóné; Dankó, Katalin

2012-09-23

140

Viral triggers for autoimmunity  

PubMed Central

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

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

2009-01-01

141

Triggers and drivers of autoimmunity: lessons from coeliac disease  

PubMed Central

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

Sollid, Ludvig M.; Jabri, Bana

2013-01-01

142

A Girl with Autoimmune Cytopenias, Nonmalignant Lymphadenopathy, and Recurrent Infections  

PubMed Central

We describe a girl, now 9 years of age, with chronic idiopathic thrombocytopenic purpura, persistent nonmalignant lymphadenopathy, splenomegaly, recurrent infections, and autoimmune hemolytic anemia. Her symptoms partly fit the definitions of both autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency disorders (CVIDs). Genetic analysis showed no abnormalities in the ALPS-genes FAS, FASLG, and CASP10. The CVID-associated TACI gene showed a homozygous polymorphism (Pro251Leu), which is found also in healthy controls. PMID:25379303

Mattheij, Marjolein A. C.; Schatorjé, Ellen J. H.; Gemen, Eugenie F. A.; van de Corput, Lisette; Nooijen, Peet T. G. A.; van der Burg, Mirjam; de Vries, Esther

2012-01-01

143

B cell depletion for autoimmune diseases in paediatric patients  

Microsoft Academic Search

Data on B cell depletion therapy in severe autoimmune diseases in paediatric patients are very limited. We conducted a retrospective\\u000a cohort study and recruited patients who were treated with rituximab (RTX) and followed up for at least 6 months through the\\u000a German societies of paediatric rheumatology and nephrology. The aim was to describe the spectrum of autoimmune disorders for\\u000a which RTX

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

2011-01-01

144

Introducing Polyautoimmunity: Secondary Autoimmune Diseases No Longer Exist  

PubMed Central

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

2012-01-01

145

Introducing polyautoimmunity: secondary autoimmune diseases no longer exist.  

PubMed

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

2012-01-01

146

Vaccines and autoimmunity.  

PubMed

Vaccines have eradicated or controlled many infectious diseases, saving each year millions of lives and quality of life of many other millions of people. In spite of the success of vaccines over the last two centuries, parents (and also some health care workers) gloss over the devastating consequences of diseases, which are now avoided thanks to vaccines, and direct their attention to possible negative effects of immunization. Three immunological objections are raised: vaccines cause antigenic overload, natural immunity is safer and better than vaccine-induced immunity, and vaccines induce autoimmunity. The last point is examined in this review. Theoretically, vaccines could trigger autoimmunity by means of cytokine production, anti-idiotypic network, expression of human histocompatibility leukocyte antigens, modification of surface antigens and induction of novel antigens, molecular mimicry, bystander activation, epitope spreading, and polyclonal activation of B cells. There is strong evidence that none of these mechanisms is really effective in causing autoimmune diseases. Vaccines are not a source of autoimmune diseases. By contrast, absolute evidence exists that infectious agents can trigger autoimmune mechanisms and that they do cause autoimmune diseases. PMID:23755743

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

2013-01-01

147

The epigenetics of autoimmunity.  

PubMed

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

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

2011-05-01

148

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

PubMed

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

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

2014-09-01

149

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

PubMed Central

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

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

2014-01-01

150

Is Tourette's syndrome an autoimmune disease?  

Microsoft Academic Search

We provide a review of recent research findings which support the involvement of autoimmunity in childhood-onset tic disorders, in particular the presence of antineuronal autoantibodies, D8\\/17 B lymphocyte overexpression, a marker of chorea associated with streptococcal infection, and possible beneficial effects of immunomodulatory intervention. One of the most controversial areas in this field is the validity of the proposed PANDAS

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

2002-01-01

151

Impact of Microbes on Autoimmune Diseases  

PubMed Central

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

Danzer, Claudia

2014-01-01

152

Recent Advances in Autoimmune Pancreatitis  

PubMed Central

Although the pathogenesis of autoimmune pancreatitis remains unclear, this report presents recent evidence of the clinical aspects of this disease: mild abdominal symptoms, usually without acute attacks of pancreatitis; occasional presence of obstructive jaundice; elevated levels of serum gammaglobulin, immunoglobulin (Ig)G, or IgG4; presence of autoantibodies; diffuse enlargement of the pancreas; irregular narrowing of the pancreatic duct (sclerosing pancreatitis), often with intrapancreatic biliary stenosis or coexisting biliary lesions (sclerosing cholangitis similar to primary sclerosing cholangitis) seen on endoscopic retrograde cholangiopancreatography; fibrotic changes with lymphocyte and IgG4-positive plasmacyte infiltration and obliterative phlebitis; occasional association with other systemic lesions (such as sialadenitis), retroperitoneal fibrosis, and interstitial renal tubular disorders; and response to steroid therapy. Based upon these findings, several sets of diagnostic criteria have been proposed. Further studies and international consensus for diagnostic criteria and pathogenetic mechanisms are needed. PMID:21904518

Uchida, Kazushige; Fukui, Toshiro; Matsushita, Mitsunobu; Takaoka, Makoto

2008-01-01

153

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

PubMed

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

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

2014-11-18

154

The Relationship of X-Linked Primary Immune Deficiencies and Autoimmunity  

Microsoft Academic Search

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

2010-01-01

155

Sudomotor dysfunction in autoimmune autonomic ganglionopathy  

PubMed Central

Background: Autoimmune autonomic ganglionopathy is characterized by impairment of multiple autonomic domains of which sudomotor function is among the most common. Many patients with this disorder have difficulties with thermoregulation and anhidrosis. Our objective was to characterize the distribution and severity of sudomotor dysfunction in this disorder. Methods: Sudomotor function was analyzed in a cohort of 21 patients with ganglionic ?3 nicotinic acetylcholine receptor (nAChR) antibody positive autoimmune autonomic ganglionopathy. Standard measurements of sudomotor function were used including the Thermoregulatory Sweat Test and Quantitative Sudomotor Axon Reflex Test. Results: The clinical presentation in all patients was characterized by widespread sudomotor dysfunction. Sudomotor impairment was predominantly postganglionic in 17 of the 21 patients studied. Higher ganglionic ?3 nAChR antibody levels resulted in progressive postganglionic predominant dysfunction (postganglionic, r = 0.637, p = 0.002; mixed ganglionic, r = 0.709, p < 0.001). The pattern of anhidrosis on Thermoregulatory Sweat Testing was consistent with a ganglionopathy in the majority of patients (14 of 21) and a distal pattern in a minority of patients (8 of 21). These patterns of anhidrosis coupled with increasing postganglionic dysfunction in a proximal to distal pattern (foot > distal leg > proximal leg > forearm) indicate lesions at both the ganglia and distal axon of the postganglionic sudomotor sympathetic neuron. Conclusions: Our data characterize the unique sudomotor dysfunction in autoimmune autonomic ganglionopathy as widespread, predominantly postganglionic, and a result of lesions at both the ganglia and distal axon. This study provides important support to the hypothesis that this disorder represents a ganglionic neuropathy. GLOSSARY AAG = autoimmune autonomic ganglionopathy; CASS = Composite Autonomic Severity Score; nAChR = nicotinic acetylcholine receptor; QSART = Quantitative Sudomotor Axon Reflex Testing; TST = Thermoregulatory Sweat Test. PMID:19884578

Kimpinski, K; Iodice, V; Sandroni, P; Fealey, R D.; Vernino, S; Low, P A.

2009-01-01

156

[Vitamin D and autoimmunity].  

PubMed

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

2013-10-01

157

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

PubMed

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

Kasznicki, Jacek; Drzewoski, Józef

2014-01-01

158

Proteasome inhibitors: a new perspective for treating autoimmune diseases.  

PubMed

Since the discovery of proteasome in the late 1980s, the ubiquitin-proteasome system has been found to exert an important physiological function in all the cells of living organisms - that of ensuring homeostasis. All cell cycle, apoptosis, differentiation, transcription, protein quality control and antigen processing activities require the efficiency of this system. As a matter of fact, several pathological conditions are characterized by deregulation of the ubiquitinproteasome system. These include cancer, neurodegenerative diseases, viral infections and autoimmune diseases. This has stimulated interest in developing proteasome inhibitors for their treatment, but clinical application has been limited due to the toxicity of these compounds. Following experiences with the first proteasome inhibitor, bortezomib, in the treatment of hematologic malignancies, several molecules with proteasome inhibitor properties were discovered and they were also exploited for the treatment of experimental models of human autoimmunity. Autoimmune disorders are a heterogeneous group of conditions, both organ- and non-organ-specific, whose incidence is increasing worldwide. This has stimulated interest in discovering novel predictive strategies and therapeutics. Here we provide a review of the use of proteasome inhibitors in treating autoimmune conditions and, in particular, systemic autoimmune diseases, inflammatory bowel disease, multiple sclerosis and organ-specific autoimmune diseases. We also present perspectives derived from more recently discovered compounds with proteasome inhibitor activity and discuss their potential in the management of these disorders. PMID:23092126

Fierabracci, Alessandra

2012-12-01

159

Polyglandular Autoimmune Syndrome Type III with Primary Hypoparathyroidism  

PubMed Central

Polyglandular autoimmune syndrome is defined as multiple endocrine gland insufficiencies accompanied by autoimmune diseases of the endocrine and nonendocrine system. After Schmidt introduced a case of nontuberculosis adrenal gland dysfunction with thyroiditis in 1926, Neufeld defined polyglandular autoimmune syndrome by I, II, and III subtypes in 1980 by their presentation of occurrence age, heredity methods, relationship with human leukocyte antigen, and accompanying diseases. We report a case of a 32-year-old female with polyglandular autoimmune syndrome III accompanied by type 1 diabetes mellitus that was treated with insulin (36 units per day) for 11 years. She had insulin deficiency and Hashimoto thyroiditis as an autoimmune disorder. In addition, she had several features similar to Albright's hereditary osteodystrophy including short stature, truncal obesity, round face, short neck, low intelligence (full IQ 84), and decreased memory. Although Albright's hereditary osteodystrophy is morphological evidence of pseudohypoparathyroidism or pseudopseudohypoparathyroidism, she had primary hypoparathyroidism on laboratory results. Here, we report a case of polyglandular autoimmune syndrome III with type 1 diabetes mellitus, autoimmune thyroiditis, and primary hypoparathyroidism, accompanied by clinical features similar to Albright's hereditary osteodystrophy. PMID:24396685

Kim, Sang Jin; Kim, Sang-Yoon; Kim, Han-Byul; Chang, Hyukwon

2013-01-01

160

Autoimmune hyperlipidemia in a child with autoimmune hepatitis.  

PubMed

The first reported case of a girl with a combination of autoimmune hyperlipidemia and autoimmune hepatitis is described. She presented at the age of 9 years with fever, headaches, and abnormal lipid profile. Months later, she had clinical manifestations, biochemical findings, and the histologic picture of autoimmune hepatitis. Subsequently, she also showed signs and symptoms of systemic lupus erythematosus. All of her clinical manifestations and biochemical abnormalities dramatically improved with immunosuppression. The overlapping syndrome of systemic lupus erythematosus, autoimmune hepatitis, and autoimmune hyperlipidemia is discussed. PMID:12172368

Rumbo, Carolina; Betzhold, James; Merati, Sukma; Shneider, Benjamin L

2002-08-01

161

Renal involvement in autoimmune connective tissue diseases  

PubMed Central

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

2013-01-01

162

Two simultaneous autoimmune processes in a patient presenting with respiratory insufficiency  

PubMed Central

The idiopathic inflammatory myopathies, including dermatomyositis, are uncommon acquired autoimmune diseases, sometimes associated with interstitial lung disease. Myasthenia gravis, a separate autoimmune disorder involving the neuromuscular junction, has some overlapping clinical features but has only rarely been reported to occur simultaneously within the same patient. Here we present the first reported case of concomitant dermatomyositis, myasthenia gravis, and interstitial lung disease. PMID:25473554

Troy, Lauren; Hamor, Paul; Bleasel, Jane; Corte, Tamera

2014-01-01

163

Coeliac disease in endocrine diseases of autoimmune origin.  

PubMed

Abstract Coeliac disease (CD, sometimes called gluten-sensitive enteropathy or nontropical sprue) is an inflammatory disorder of the small intestine of autoimmune origin. It occurs in genetically predisposed people and is induced by a gluten protein, which is a component of wheat. The prevalence of histologically confirmed CD is estimated in screening studies of adults in the United States and Europe to be between 0.2% and 1.0%. The results of previous studies have indicated that the prevalence of CD is increased in patients with other autoimmune disorders such as: autoimmune thyroid diseases, type 1 diabetes mellitus, and Addison's disease. A coincidence of the above diseases constitutes autoimmune polyglandular syndrome (APS). The high prevalence of CD in APS is probably due to the common genetic predisposition to the coexistent autoimmune diseases. The majority of adult patients have the atypical or silent type of the disease. This is the main reason why CD so often goes undiagnosed or the diagnosis is delayed. CD, if undiagnosed and untreated, is associated with many medical disorders including haematological (anaemia), metabolical (osteopenia/osteoporosis), obstetric-gynaecological (infertility, spontaneous abortions, late puberty, early menopause), neurological (migraine, ataxia, epilepsy) as well as with an increased risk of malignancy, especially: enteropathy-associated T-cell lymphoma, small intestine adenocarcinoma, and oesophageal and oropharyngeal carcinomas. Early introduction of a gluten-free diet and lifelong adherence to this treatment decreases the risk of these complications. PMID:22744631

Mi?kiewicz, Piotr; K?pczy?ska-Nyk, Anna; Bednarczuk, Tomasz

2012-01-01

164

Mechanisms of autoimmune liver disease.  

PubMed

The immune system of the liver is characterized by a predominant innate component. Several innate immune cell populations have been implicated in the pathogenesis of immune-mediated hepatic diseases, which are frequently associated with systemic symptoms or with co-morbidities affecting other organ systems. Thus, next to tissue-specific factors, general tolerance mechanisms are affected in devastating hepatic disorders like primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), or primary biliary cirrhosis (PBC). The innate immune cell populations abundantly detected within the liver and endowed with potent immunomodulatory capacities include innate lymphoid cells (ILCs) and natural killer T (NKT) cells. While both ILCs and NKT cells can be activated by different cytokines and/or chemokines, NKT cells also respond to (glyco-) lipid antigens engaging their canonical, semi-invariant TCR. Once activated, ILCs and NKT cells release copious amounts of Th1, Th2, and/or Th17 cytokines that shape subsequent innate and adaptive immune responses. Those immunomodulatory features as well as the recently described antigen-presenting capacity of ILCs and/or the bi-directional functional role of NKT cells might not only underlie the pathogenic mechanisms in the respective disorders, but also provide promising targets for clinical intervention. We will discuss these novel aspects as well as the role of alarmin-like cytokines such as IL-33 in the context of ILC and NKT cell activation and the consequences for the induction and progress of hepatic tissue damage and fibrosis. PMID:25425466

Baier, Julia L C; Mattner, Jochen

2014-11-01

165

Leishmaniasis and autoimmune diseases in pediatric age.  

PubMed

Leishmaniasis is a group of diseases caused by the protozoa Leishmania, endemic in the Mediterranean countries. Clinical manifestations can be divided into three different forms: cutaneous leishmaniasis, mucosal leishmaniasis and the visceral leishmaniasis, the most severe form which is potentially lethal if untreated. Immunology and pathogenesis are complex: many different aspects of immune response, resistance and susceptibility to Leishmania have been studied but many others remain to be clarified. The gold standard in diagnosis of visceral Leishmaniasis is the presence of amastigotes in bone marrow or tissue sections. Patients can be initially misdiagnosed as having an autoimmune disease because it may mimic diseases like systemic lupus erythematosus, autoimmune hepatitis, dermatomyositis or others disorders. As in pediatric age the risk of life-threatening complications is very high, leishmaniasis, must be kept in mind to the clinician, in order to avoid wrong diagnosis and an inappropriate immunosuppressive therapy. PMID:25240149

Nozzi, M; Del Torto, M; Chiarelli, F; Breda, L

166

Intracellular Nucleic Acid Sensors and Autoimmunity  

PubMed Central

A collection of molecular sensors has been defined by studies in the last decade that can recognize a diverse array of pathogens and initiate protective immune and inflammatory responses. However, if the molecular signatures recognized are shared by both foreign and self-molecules, as is the case of nucleic acids, then the responses initiated by these sensors may have deleterious consequences. Notably, this adverse occurrence may be of primary importance in autoimmune disease pathogenesis. In this case, microbe-induced damage or mishandled physiologic processes could lead to the generation of microparticles containing self-nucleic acids. These particles may inappropriately gain access to the cytosol or endolysosomes and, hence, engage resident RNA and DNA sensors. Evidence, as reviewed here, strongly indicates that these sensors are primary contributors to autoimmune disease pathogenesis, spearheading efforts toward development of novel therapeutics for these disorders. PMID:22029446

Kono, Dwight H.; Beutler, Bruce

2011-01-01

167

Immunotherapeutic strategies in autoimmune uveitis  

PubMed Central

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

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

2014-01-01

168

ALPS: an autoimmune human lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis.  

PubMed

Apoptosis of activated lymphocytes is critical to immune homeostasis. The cell surface receptor Fas is an important mediator of lymphocyte apoptosis; defective Fas expression causes accumulation of lymphocytes and autoimmune disease in mice. Apoptosis defects due to mutations of Fas have also been found in a rare human autoimmune lymphoproliferative syndrome (ALPS). Nine unrelated children with ALPS had lymphadenopathy, autoimmunity and expansion of a normally infrequent population of CD4-CD8-T cells. All nine exhibited impaired lymphocyte apoptosis in vitro, and eight had heterozygous Fas gene mutations. Thus genetic defects in apoptosis pathways are implicated in the pathogenesis of at least one human autoimmune disorder. PMID:9106310

Puck, J M; Sneller, M C

1997-02-01

169

Special report: Autoimmune hepatitis  

Microsoft Academic Search

Opinion statement  \\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Autoimmune hepatitis can be treated effectively with either prednisone alone or a lower dose of prednisone in combination\\u000a with azathioprine.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a All types of autoimmune hepatitis should be treated similarly.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a The combination schedule of prednisone and azathioprine is preferred since it is associated with fewer side effects than a\\u000a higher dose of prednisone alone.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Lifestyle

Albert J. Czaja

1999-01-01

170

Annotation: PANDAS--A Model for Human Autoimmune Disease  

ERIC Educational Resources Information Center

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

Swedo, Susan E.; Grant, Paul J.

2005-01-01

171

Low dose combination steroids control autoimmune mouse hearing loss  

Microsoft Academic Search

The severe side effects of glucocorticoids prevent long term management of hearing loss. Alternative steroid treatments that minimize or eliminate these effects would significantly benefit therapeutic control of hearing disorders. A steroid treatment study of autoimmune mouse hearing loss was conducted to determine the efficacy of combining aldosterone and prednisolone at low doses. An assessment also was made of low

Dennis R. Trune; J. Beth Kempton

2010-01-01

172

Antibody titers predict clinical features of autoimmune autonomic ganglionopathy  

Microsoft Academic Search

Autoimmune autonomic ganglionopathy is a disorder of isolated autonomic failure associated with antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia resulting in severe orthostatic intolerance, syncope, constipation, gastroparesis, urinary retention, dry mouth, dry eyes, blurred vision and anhidrosis. We report the autonomic test results, antibody titers and clinical findings in 8 patients with antibodies to the nicotinic acetylcholine

Christopher H. Gibbons; Roy Freeman

2009-01-01

173

Air pollution in autoimmune rheumatic diseases: A review  

Microsoft Academic Search

Air pollution consists of a heterogeneous mixture of gasses and particles that include carbon monoxide, nitrates, sulfur dioxide, ozone, lead, toxic by-product of tobacco smoke and particulate matter. Oxidative stress and inflammation induced by inhaled pollutants may result in acute and chronic disorders in the respiratory system, as well as contribute to a state of systemic inflammation and autoimmunity. This

Sylvia C. L. Farhat; Clovis A. Silva; Maria Angelica M. Orione; Lucia M. A. Campos; Adriana M. E. Sallum; Alfésio L. F. Braga

2011-01-01

174

Etiopathogenesis of Insulin Autoimmunity  

PubMed Central

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. PMID:22567309

Kanatsuna, Norio; Papadopoulos, George K.; Moustakas, Antonis K.; Lenmark, Ĺke

2012-01-01

175

[Necrotizing autoimmune myopathies].  

PubMed

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

2013-01-01

176

Autoimmunity and pregnancy loss.  

PubMed

Clinicians have recognized for several decades that certain autoimmune conditions, such as systemic lupus erythematosus (SLE), are associated with pregnancy loss. During the 1980s, investigations focused attention on fetal wastage in women with antiphospholipid antibodies and the antiphospholipid antibody syndrome (APS) was characterized. Its defining features include fetal wastage in the presence of significant levels of anticardiolipin antibodies. Since that time, interest in other autoimmune diatheses and various specific autoantibodies as possible causes of pregnancy loss has increased. Investigators have attempted to establish an association between recurrent pregnancy loss and the presence of a specific autoantibody or patterns of autoantibodies. Thus far, only modest evidence supports the concept that other autoantibodies are linked to, much less cause, pregnancy loss. In this review, we will define pregnancy loss in its various forms and discuss pregnancy loss in well-characterized autoimmune diseases such as SLE and APS. We will focus on the diagnosis and management of these conditions in women attempting to achieve successful pregnancies. Later we discuss the evidence concerning the less well defined association of antiphospholipid antibodies other than the lupus anticoagulant and anticardiolipin antibodies to recurrent pregnancy loss. We then outline the significance of antinuclear antibodies and antithyroid antibodies pertaining to adverse pregnancy outcome and conclude by summarizing and making some suggestions for further study. PMID:11355797

Faussett, M B; Branch, D W

2000-01-01

177

Imaging of autoimmune diseases.  

PubMed

Autoimmune diseases represent a heterogeneous group of pathologies with a wide range of immunological changes and clinical presentations. The clinical onset of the disease commonly occurs when signs and symptoms of target tissue hypofunction appear; complications can also be present. The aim of an imaging diagnostic technique in this context is to correctly evaluate the disease extent and severity for appropriate treatment and to follow up the efficacy of therapy. In addition, identification of subjects at risk and the preclinical diagnosis may allow disease prevention. Ultrasound (US), conventional radiology and computed tomography (CT) are often used for a detailed morphological study of tissues involved; magnetic resonance (MRI) may also demonstrate biochemical and structural tissue changes. Nuclear medicine techniques are known for their sensitivity and specificity and in recent years an expanding field is represented by the development of radiolabelled receptor ligands. New radiopharmaceuticals able to bind in vivo to specific receptors have been introduced allowing the non invasive detection of changes in affected tissues. The relevant criteria to choose different diagnostic approaches in several autoimmune diseases are discussed in this review. In particular the role and contribution of nuclear medicine for the study of autoimmune diseases have been described. PMID:10230286

Procaccini, E; Chianelli, M; Pantano, P; Signore, A

1999-03-01

178

Autoimmune diabetes: the involvement of benign and malignant autoimmunity.  

PubMed

Our studies in the NOD mouse demonstrate that the autoimmune response can be either benign or malignant. In the former case autoimmunity. After that time animals move, in an unpredictable way, into the malignant state of autoimmunity. As a result, animals >/=100 days of age make up a heterogeneous group where some are in a benign state of autoimmunity, which can continue for a further |LX200 days, others are in a state of transition to the malignant state of autoimmunity, and others have a fully malignant autoimmune response and are diabetic. This heterogeneity developing within members of the population, in terms of pancreatic damage, is not consistent with the proposal that autoimmune islet damage in the NOD mouse is a slow, progressive process affecting all disease prone members of the population. In the NOD mouse, massive islet destruction is a late event in the autoimmune process and only develops following the conversion of the autoimmune response from the benign to the malignant state. PMID:10330293

Dilts, S M; Lafferty, K J

1999-06-01

179

Immune Disorder HSCT Protocol  

ClinicalTrials.gov

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

2014-12-09

180

17. Immunologic endocrine disorders  

Microsoft Academic Search

Immune-mediated tissue destruction or disregulation is the cause of multiple common, as well as rare, endocrine disorders including type 1 diabetes, Graves' disease, Hashimoto thyroiditis, and Addison's disease. Each of these disorders can be divided into a series of stages beginning with genetic susceptibility, environmental triggering events, and active autoimmunity, followed by metabolic abnormalities with overt disease. Common genetic susceptibility

Devasenan Devendra; George S. Eisenbarth

2003-01-01

181

Role of myeloid-derived suppressor cells in autoimmune disease  

PubMed Central

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

Crook, Kristen R; Liu, Peng

2015-01-01

182

Autoimmune thrombocytopenia: a complication of fludarabine therapy in the treatment of Waldenstrom’s macroglobulinemia  

PubMed Central

Fludarabine is an effective purine analogue which has become extensive used in lymph proliferative malignancies. However, an increased incidence of autoimmune disorders including autoimmune hemolytic anemia (AHIA) and idiopathic thrombocytopenia (ITP) is reported with the use of fludarabine. The exact mechanism for fludarabine to exacerbate thrombocytopenia is not distinct. In our report, we describe a patient with WM developed a refractory, life-threatening and fludarabine-associated thrombocytopenia which could not be explained by the cytotoxic effects of fludarabine. Possible mechanisms of fludarabine on autoimmune disorders are discussed.

Jiang, Yujie; Peng, Hongjuan; Cui, Xin; Zhou, Ying; Yuan, Dai; Sui, Xiaohui; Zhang, Lingyan; Xu, Hongzhi

2014-01-01

183

Autoimmune lymphoproliferative syndrome with neonatal onset.  

PubMed

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

2014-05-01

184

Treatment of autoimmune hemolytic anemias  

PubMed Central

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

Zanella, Alberto; Barcellini, Wilma

2014-01-01

185

Autoimmune Polyglandular Syndrome Type 1  

PubMed Central

Autoimmune Polyglandular Syndrome (APS) Type 1 is a rare hereditary disorder that damages organs in the body. This disease entity is the result of a mutation in the AIRE gene. It is characterized by three classic clinical features - hypoparathyroidism, Addison's disease, and chronic mucocutaneous candidiasis. For a patient to be diagnosed as having APS Type 1 syndrome at least two of these features needs to be present. The third entity may develop as the disease progresses. We report a case of a 35-year-old female patient with a history of seizure from the age of 11 years, who was managed with anticonvulsant drugs. With worsening of the seizure episodes, patient was diagnosed to have hypoparathyroidism together with the manifestations of oral candidiasis, nails dystrophy, enamel hypoplasia, and hypogonadism. A diagnosis of APS-1 was considered. The facility for genetic analysis of the AIRE gene mutation was not accessible, as the test costs were prohibitive and not affordable for the patient. Patient management was directed to treating individual disease components. However, cerebral and dental changes were irreversible. PMID:23230544

Ponranjini, Vedeswari C.; Jayachandran, S; Kayal, L; Bakyalakshmi, K

2012-01-01

186

The Autoimmune Basis of Narcolepsy  

PubMed Central

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

2013-01-01

187

A look at autoimmunity and inflammation in the eye  

PubMed Central

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.

2010-01-01

188

Three cases of pneumatosis intestinalis presenting in autoimmune diseases.  

PubMed

Pneumatosis intestinalis (PI) is a comparatively rare disease characterized by the presence of intramural gas in the gastrointestinal tract. PI is known to be associated with several clinical conditions, such as pulmonary diseases, gastrointestinal diseases, and traumatic injury, as well as autoimmune disorders. In particular, PI is commonly seen in systemic sclerosis (SSc) but rarely in systemic lupus erythematosus and dermatomyositis (DM). In this report, we present three cases of PI presenting in autoimmune diseases, including DM, Sjögren's syndrome, and limited SSc, and further discuss its background characteristics. PMID:22068684

Sagara, Akihiro; Kitagawa, Kiyoki; Furuichi, Kengo; Kitajima, Shinji; Toyama, Tadashi; Okumura, Toshiya; Hara, Akinori; Sakai, Yoshio; Kaneko, Shuichi; Wada, Takashi

2012-08-01

189

Antibodies to neurofascin exacerbate adoptive transfer experimental autoimmune neuritis.  

PubMed

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

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

2014-12-15

190

Prolactin and autoimmunity.  

PubMed

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

2012-05-01

191

Autoimmunity in Common Variable Immunodeficiency  

PubMed Central

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. PMID:19671377

Agarwal, Shradha; Cunningham-Rundles, Charlotte

2010-01-01

192

Immunomodulation of Autoimmune Arthritis by Herbal CAM  

PubMed Central

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

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

2011-01-01

193

Leukocyte immunoglobulin-like receptors as new players in autoimmunity.  

PubMed

Leukocyte immunoglobulin-like receptors (LILR) are a family of at least 13 receptors mainly expressed on lymphoid and myelomonocytic cells. They are involved in the activation of the immune system. Inhibitory LILR (termed LILRB) signal through immunoreceptor tyrosine-based inhibitory motives in the cytoplasmic domain, whereas LILRA with short cytoplasmic domains are stimulatory receptors. Polymorphisms and deletions of leukocyte immunoglobulin-like receptors have been shown to be associated with autoimmune disorders, and some of the receptors are involved in the generation of regulatory T cells. Therefore, leukocyte immunoglobulin-like receptors may be central in the pathogenesis of autoimmunity. The data linking these receptors to autoimmune diseases is reviewed here. PMID:19548123

Thomas, Rachel; Matthias, Torsten; Witte, Torsten

2010-04-01

194

Conformation of an antigenic determinant for experimental autoimmune neuritis.  

PubMed

The conformation of SP-26, the synthetic peptide (residues 53-78) of myelin P2 protein that causes experimental autoimmune neuritis (EAN) in the peripheral nervous system, has been investigated in D2O using Fourier transform infra-red spectroscopy. Turns were found in 26% of the residues in the peptide, with rest of the residues in random coil (72%). The presence of 26% turns agrees well with the number of residues forming three turns in the antigenic region of the intact protein and the number of turns correlates well with the severity of EAN. Since turns also exist in peptides inducing experimental autoimmune encephalomyelitis, the central nervous system counterpart of EAN, turn structure may be a common structural motif for these closely related autoimmune neurological disorders. PMID:8694832

Shin, H C; Stuart, B; McFarlane, E F

1996-07-01

195

disorder disorder Co disorder  

E-print Network

disorder disorder RKKY Co 10 Co disorder disorder disorder Kondo-like Co 3 BiSb BiSb 4 BiSb Bi(001) Bi(001) Bi(001) 1 m 1, 000 % Bi 10 % Bi/Ag(111) Rashba #12;2 Ag(111) Bi 1/3 Ag(111) 3 Ă? 3-Bi 1 ps Rashba ( ) [1] K. He, T. Hirahara, T. Okuda, S. Hasegawa, A. Kakizaki, and I. Matsuda: Spin-polarization

Hasegawa, Shuji

196

Anti-Saccharomyces cerevisiae antibodies (ASCA) and autoimmune liver diseases  

PubMed Central

Antibodies to the baker's yeast Saccharomyces cerevisiae (ASCA), recently proposed as a serological marker of Crohn's disease, have also been detected in other autoimmune disorders. The aim of this study was to determine prevalence and clinical significance of ASCA in autoimmune liver disease. The presence of IgG and IgA ASCA was evaluated using a commercially available immunoassay in 215 patients with autoimmune liver disease (primary biliary cirrhosis, PBC, 123 cases; autoimmune hepatitis, AIH, 67 cases; primary sclerosing cholangitis, PSC, 25 cases), 48 with inflammatory bowel disease and 19 healthy blood donors. Anti neutrophil cytoplasmic antibodies with the perinuclear pattern (p-ANCA) were assessed by indirect immunofluorescence in PSC patients. The main clinical and biochemical parameters between ASCA-positive and negative patients were analysed and compared. ASCA are predominant in Crohn's disease (70%); among liver patients, PSC and AMA-negative PBC show the highest ASCA prevalence (53% and 44%). In PBC ASCA correlate with higher levels of circulating IgA (P < 0·05). In PSC the detection of either ASCA or p-ANCA is neither associated with any clinical or biochemical feature, nor with an underlying inflammatory bowel disease. ASCA can not be considered an additional serological marker of autoimmune liver disease, but the possibility of detecting such a reactivity in autoimmune liver disorders should be considered; their correlation with elevated IgA in PBC suggests that ASCA may be an indirect sign of enhanced mucosal immunity; in PSC patients neither ASCA nor p-ANCA predict the occurrence of a concomitant inflammatory bowel disease. PMID:12780695

MURATORI, P; MURATORI, L; GUIDI, M; MACCARIELLO, S; PAPPAS, G; FERRARI, R; GIONCHETTI, P; CAMPIERI, M; BIANCHI, F B

2003-01-01

197

Anti-Saccharomyces cerevisiae antibodies (ASCA) and autoimmune liver diseases.  

PubMed

Antibodies to the baker's yeast Saccharomyces cerevisiae (ASCA), recently proposed as a serological marker of Crohn's disease, have also been detected in other autoimmune disorders. The aim of this study was to determine prevalence and clinical significance of ASCA in autoimmune liver disease. The presence of IgG and IgA ASCA was evaluated using a commercially available immunoassay in 215 patients with autoimmune liver disease (primary biliary cirrhosis, PBC, 123 cases; autoimmune hepatitis, AIH, 67 cases; primary sclerosing cholangitis, PSC, 25 cases), 48 with inflammatory bowel disease and 19 healthy blood donors. Anti neutrophil cytoplasmic antibodies with the perinuclear pattern (p-ANCA) were assessed by indirect immunofluorescence in PSC patients. The main clinical and biochemical parameters between ASCA-positive and negative patients were analysed and compared. ASCA are predominant in Crohn's disease (70%); among liver patients, PSC and AMA-negative PBC show the highest ASCA prevalence (53% and 44%). In PBC ASCA correlate with higher levels of circulating IgA (P < 0.05). In PSC the detection of either ASCA or p-ANCA is neither associated with any clinical or biochemical feature, nor with an underlying inflammatory bowel disease. ASCA can not be considered an additional serological marker of autoimmune liver disease, but the possibility of detecting such a reactivity in autoimmune liver disorders should be considered; their correlation with elevated IgA in PBC suggests that ASCA may be an indirect sign of enhanced mucosal immunity; in PSC patients neither ASCA nor p-ANCA predict the occurrence of a concomitant inflammatory bowel disease. PMID:12780695

Muratori, P; Muratori, L; Guidi, M; Maccariello, S; Pappas, G; Ferrari, R; Gionchetti, P; Campieri, M; Bianchi, F B

2003-06-01

198

Pancreatic islet autoimmunity.  

PubMed

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

Boitard, Christian

2012-12-01

199

Air pollution in autoimmune rheumatic diseases: a review.  

PubMed

Air pollution consists of a heterogeneous mixture of gasses and particles that include carbon monoxide, nitrates, sulfur dioxide, ozone, lead, toxic by-product of tobacco smoke and particulate matter. Oxidative stress and inflammation induced by inhaled pollutants may result in acute and chronic disorders in the respiratory system, as well as contribute to a state of systemic inflammation and autoimmunity. This paper reviews the mechanisms of air contaminants influencing the immune response and autoimmunity, and it focuses on studies of inhaled pollutants triggering and/or exacerbating rheumatic diseases in cities around the world. Remarkably, environmental factors contribute to the onset of autoimmune diseases, especially smoking and occupational exposure to silica in rheumatoid arthritis and systemic lupus erythematosus. Other diseases such as scleroderma may be triggered by the inhalation of chemical solvents, herbicides and silica. Likewise, primary vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA) may be triggered by silica exposure. Only few studies showed that air pollutants could trigger or exacerbate juvenile idiopathic arthritis and systemic lupus erythematosus. In contrast, no studies of tropospheric pollution triggering inflammatory myopathies and spondyloarthropathies were carried out. In conclusion, air pollution is one of the environmental factors involved in systemic inflammation and autoimmunity. Further studies are needed in order to evaluate air pollutants and their potentially serious effects on autoimmune rheumatic diseases and the mechanisms involved in the onset and the exacerbation of these diseases. PMID:21763467

Farhat, Sylvia C L; Silva, Clovis A; Orione, Maria Angelica M; Campos, Lucia M A; Sallum, Adriana M E; Braga, Alfésio L F

2011-11-01

200

Autoimmune autonomic failure.  

PubMed

Autoimmune autonomic ganglionopathy is a syndrome of panautonomic failure caused by antibodies to ganglionic acetylcholine receptors. The clinical syndrome is characterized by significant postural hypotension, diffuse cholinergic and adrenergic impairment, gastrointestinal dysmotility, urinary retention, and pupillary dysfunction. While acute to subacute onset of disease is commonly seen, chronic, slowly progressive variants have been described. Serological testing for ganglionic acetylcholine receptor antibodies helps confirm the diagnosis. These antibodies cause a similar phenotype of autonomic failure in animal models indicating that an antibody-mediated functional impairment of ganglionic transmission is the underlying etiology. Decrease in antibody levels correlates with clinical improvement. Patients may respond to immunomodulatory therapies such as prednisone, intravenous immunoglobulin, plasma exchange, and oral immunosuppressants. A combination treatment is often required as well as symptomatic therapy. PMID:24095135

Muppidi, Srikanth; Vernino, Steven

2013-01-01

201

Cytokine gene polymorphisms and human autoimmune disease in the era of genome-wide association studies.  

PubMed

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

Vandenbroeck, Koen

2012-04-01

202

Treating endometriosis as an autoimmune disease  

Microsoft Academic Search

Objective: To review the literature on the role of autoimmunity in the etiology of endometriosis, compare the similarities in the pathophysiologies between endometriosis and autoimmune diseases, and discuss the use of immunomodulators currently used to treat autoimmune diseases as potential therapies for endometriosis.Design: The literature on endometriosis and other autoimmune diseases was reviewed, and summary data are presented.Results: Endometriosis shares

Warren B Nothnick

2001-01-01

203

Questions and Answers on Autoimmunity and Autoimmune Diseases  

MedlinePLUS

... is widely spread throughout the body. Examples include rheumatoid arthritis, systemic lupus erythematosus (SLE or lupus), and dermatomyositis. What are some of the treatments for autoimmune diseases? Of first importance in treating ...

204

Autoimmune Thyroid Diseases in Children  

PubMed Central

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

Cappa, Marco; Bizzarri, Carla; Crea, Francesca

2011-01-01

205

Sensory Neuronopathy and Autoimmune Diseases  

PubMed Central

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

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

2012-01-01

206

Analysis of Families in the Multiple Autoimmune Disease Genetics Consortium (MADGC) Collection: the PTPN22 620W Allele Associates with Multiple Autoimmune Phenotypes  

PubMed Central

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 Sjögren 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.

2005-01-01

207

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

PubMed Central

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

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

2012-01-01

208

Case Study: A New Infection-Triggered, Autoimmune Subtype of Pediatric OCD and Tourette's Syndrome  

Microsoft Academic Search

A review of clinical observations and literature reports leads to the hypothesis that, via a process analogous to Sydenham's chorea, infections with group A ?-hemolytic streptococci, among others, may trigger autoimmune responses that cause or exacerbate some cases of childhood-onset obsessive-compulsive disorder (OCD) or tic disorders (including Tourette's syndrome). If this hypothesis is correct, then immunological treatments should lead to

Albert J. Allen; Henrietta L. Leonard; Susan E. Swedo

1995-01-01

209

Inflammatory cytokines in the nervous system: multifunctional mediators in autoimmunity and cerebral ischemia.  

PubMed

Cytokines are immune mediators that orchestrate inflammatory responses. In autoimmune disorders of the nervous system such as the Guillain-Barré syndrome (GBS), and the corresponding animal model, experimental autoimmune neuritis (EAN), proinflammatory cytokines augment nerve infiltration by T-cells and contribute to macrophage-mediated demyelination. The local balance between pro- and antiinflammatory effects determines the clinical course. Cytokine expression in the nervous system is, however, not restricted to autoimmune disorders. Cytokines likewise contribute to infarct growth after focal cerebral ischemia, and under certain conditions convey neuroprotection. This short review summarizes selected aspects of cytokine actions during immune-mediated demyelination and cerebral ischemia. Elucidation of cytokine-mediated pathways of neurotoxicity and neuroprotection may not only improve stroke treatment, but, in addition may have a major impact on autoimmune diseases such as multiple sclerosis and GBS, in which axonal loss rather than demyelination determines long-term disability. PMID:12407295

Stoll, G

2002-10-01

210

Sex differences in autoimmune diseases  

PubMed Central

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

2011-01-01

211

Steroid-Resistant Autoimmune Thrombocytopenia in Systemic Lupus Erythematosus Treated with Rituximab  

PubMed Central

Systemic Lupus Erythematosus (SLE) is a multisystem disorder characterized by production of numerous autoantibodies, some of which have pathogenic consequences and result in considerable morbidity. Herein, we present a case of 48-year-old female with SLE having autoimmune hemolytic anemia, autoimmune thrombocytopenia, renal involvement, and recurrent flares of skin manifestations. She did not respond to the conventional therapy and was controlled and treated with Rituximab, a chimeric, monoclonal antiCD20 antibody, which specifically depletes B lymphocytes.

Sardesai, Vasudha V; Sardesai, Vidyadhar R; Agarwal, Trupti D

2015-01-01

212

Steroid-resistant autoimmune thrombocytopenia in systemic lupus erythematosus treated with rituximab.  

PubMed

Systemic Lupus Erythematosus (SLE) is a multisystem disorder characterized by production of numerous autoantibodies, some of which have pathogenic consequences and result in considerable morbidity. Herein, we present a case of 48-year-old female with SLE having autoimmune hemolytic anemia, autoimmune thrombocytopenia, renal involvement, and recurrent flares of skin manifestations. She did not respond to the conventional therapy and was controlled and treated with Rituximab, a chimeric, monoclonal antiCD20 antibody, which specifically depletes B lymphocytes. PMID:25657435

Sardesai, Vasudha V; Sardesai, Vidyadhar R; Agarwal, Trupti D

2015-01-01

213

Thyroid-associated orbitopathy is linked to gastrointestinal autoimmunity.  

PubMed

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

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

2014-10-01

214

Functionally defective germline variants of sialic acid acetylesterase in autoimmunity  

Microsoft Academic Search

Sialic acid acetylesterase (SIAE) is an enzyme that negatively regulates B lymphocyte antigen receptor signalling and is required for the maintenance of immunological tolerance in mice. Heterozygous loss-of-function germline rare variants and a homozygous defective polymorphic variant of SIAE were identified in 24\\/923 subjects of European origin with relatively common autoimmune disorders and in 2\\/648 controls of European origin. All

Ira Surolia; Stephan P. Pirnie; Vasant Chellappa; Kendra N. Taylor; Annaiah Cariappa; Jesse Moya; Haoyuan Liu; Daphne W. Bell; David R. Driscoll; Sven Diederichs; Khaleda Haider; Ilka Netravali; Sheila Le; Roberto Elia; Ethan Dow; Annette Lee; Jan Freudenberg; Philip L. de Jager; Yves Chretien; Ajit Varki; Marcy E. MacDonald; Tammy Gillis; Timothy W. Behrens; Donald Bloch; Deborah Collier; Joshua Korzenik; Daniel K. Podolsky; David Hafler; Mandakolathur Murali; Bruce Sands; John H. Stone; Peter K. Gregersen; Shiv Pillai

2010-01-01

215

Annotation: PANDAS: a model for human autoimmune disease  

Microsoft Academic Search

Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infec- tions (PANDAS) is a recently recognized syndrome in which pre-adolescent children have abrupt onsets of tics and\\/or obsessive-compulsive symptoms, a recurring and remitting course of illness temporally related to streptococcal infections, and associated neurologic findings including adventitious move- ments, hyperactivity and emotional lability. Methods: Inspired by observations of similar symptoms in

Susan E. Swedo; Paul J. Grant

2005-01-01

216

Autoimmune hepatitis: Clinical manifestations and diagnostic criteria.  

PubMed

In 1998, the International Autoimmune Hepatitis Group--a panel of 40 hepatologists and hepatopathologists from 17 countries who have a particular interest in autoimmune hepatitis (AIH)--undertook a review, in light of subsequent experience, of the descriptive criteria and diagnostic scoring system that it had proposed in 1993 for the diagnosis of AIH. This review (published in 1999) noted that the original descriptive criteria appeared to be quite robust and required only relatively minor modifications to bring them up to date with developments and experience in diagnostic modalities for liver disease in general. Analysis of published data on the application of the original criteria in nearly 1000 patients revealed that the diagnostic scoring system had an overall diagnostic accuracy of 89.8%, with a sensitivity of 98.0%. Specificity for excluding definite AIH in patients with chronic viral hepatitis and circulating autoantibodies or patients with overlapping cholestatic syndromes was 98% to 100%, but specificity for excluding probable AIH in these disorders ranged from only 60% to 80%. Modifications, including adjustments to the weightings against biochemical and histological cholestatic features, have been made to the scoring system to improve its specificity. PMID:11240380

McFarlane, I G

2001-02-01

217

Idiopathic chronic urticaria and thyroid autoimmunity  

PubMed Central

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. PMID:22259654

Tauchmanova, Libuse; Colasanti, Paola; Zuccoli, Alfonso; Colao, Annamaria

2011-01-01

218

Autoimmune and paraneoplastic channelopathies  

Microsoft Academic Search

Summary  Thirty years ago, antibodies against the muscle acetylcholine receptor (AChR) were recognized as the cause of myasthenia gravis.\\u000a Since then, there has been great interest in identifying other neurological disorders associated with auto-antibodies. Several\\u000a other antibody-mediated neuromuscular disorders have been identified, each associated with an antibody against a ligand- or\\u000a voltage-gated ion channel. The Lambert-Eaton syndrome is caused by antibodies

Steven Vernino

2007-01-01

219

Diagnosis of autoimmune pancreatitis.  

PubMed

Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to IgG4 (lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum IgG4 and positive serum autoantibodies, abundant infiltration of IgG4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology (IAP). PMID:25469024

Matsubayashi, Hiroyuki; Kakushima, Naomi; Takizawa, Kohei; Tanaka, Masaki; Imai, Kenichiro; Hotta, Kinichi; Ono, Hiroyuki

2014-11-28

220

Antibodies as predictors of complex autoimmune diseases and cancer.  

PubMed

The pathologic role of autoantibodies in many autoimmune diseases is widely accepted. An enzyme immunoassay was used for measurement of antibodies against disease-specific antigens and etiologic agents for cross-reactive antigens associated with them. This antibody assay was applied to a panel of antigens for the detection of different neuroautoimmune diseases that included multiple sclerosis, motor peripheral neuropathies, multifocal motor neuropathy, amyotrophic lateral sclerosis, pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection. We studied women with pregnancies complicated by neural tube defect, neuroborreliosis, autism and patients with possible somatic hypermutation. Antibodies were also measured against antigens and etiologic agents associated with primary biliary cirrhosis and chronic obstructive pulmonary disease. And, finally, antibodies were measured against several tumor antigens or peptides which are expressed in prostatic, breast and colon tissues. This panel of different autoantibodies was applied to 290 patients with neuroautoimmune disorders, cancer, and possible somatic hypermutation. The levels of these antibodies against different tissue-specific antigens and etiologic agents associated with them were significantly elevated in patients versus controls. We hope that this novel 96 antigen-specific ELISA will be used in additional studies that will prove its clinical efficacy, not only for the early diagnosis of many neuroautoimmune, liver and lung autoimmune disorders, but also for prognosis and the implementation of preventive steps for many complex diseases. PMID:18831922

Vojdani, A

2008-01-01

221

The multiple autoimmune syndromes. A clue for the autoimmune tautology.  

PubMed

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

2012-12-01

222

Type 1 Diabetes and Autoimmunity  

PubMed Central

Abstract. Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by the autoimmune response against pancreatic ? cells. T1D is often complicated with other autoimmune diseases, and anti-islet autoantibodies precede the clinical onset of disease. The most common coexisting organ-specific autoimmune disease in patients with T1D is autoimmune thyroid disease, and its frequency is estimated at > 90% among patients with T1D and autoimmune diseases. The prevalence of anti-thyroid antibodies in children with T1D at disease onset is about 20% and is particularly common in girls. Furthermore, patients with anti-thyroid antibodies are 18 times more likely to develop thyroid disease than patients without anti-thyroid antibodies. Therefore, for early detection of autoimmune thyroid disease in children with T1D, measurement of anti-thyroid antibodies and TSH at T1D onset and in yearly intervals after the age of 12 yr is recommended. Anti-islet autoantibodies are predictive and diagnostic markers for T1D. The most frequently detected autoantibodies in Japanese patients are GAD autoantibodies (~80%) followed by IA-2 autoantibodies (~60%), insulin autoantibodies (~55%) and ZnT8 autoantibodies (~50%). In a combined analysis, 94% of Japanese patients with T1D can be defined as having type 1A diabetes. Furthermore, autoantibodies to ZnT8 and IA-2 are associated with childhood-onset and acute-onset patients. Thus, it is important to develop a diagnostic strategy for patients with type 1A diabetes in consideration of the age or mode of disease onset. PMID:25374439

Kawasaki, Eiji

2014-01-01

223

Autoimmune thyroiditis presenting as palmoplantar keratoderma.  

PubMed

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. PMID:20300544

Lestre, Sara; Lozano, Eva; Meireles, Cláudia; Barata Feio, Ana

2010-01-01

224

Autoimmune Lymphoproliferative Syndrome Misdiagnosed as Hemophagocytic Lymphohistiocytosis  

PubMed Central

Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder of apoptosis, most commonly due to mutations in the FAS (TNFRSF6) gene. It presents with chronic lymphadenopathy, splenomegaly, and symptomatic multilineage cytopenias in an otherwise healthy child. Unfortunately, these clinical findings are also noted in other childhood lymphoproliferative conditions, such as leukemia, lymphoma, and hemophagocytic lymphohistiocytosis, which can confound the diagnosis. This report describes a 6-year-old girl with symptoms misdiagnosed as hemophagocytic lymphohistiocytosis and treated with chemotherapy before the recognition that her symptoms and laboratory values were consistent with a somatic FAS mutation leading to ALPS. This case should alert pediatricians to include ALPS in the differential diagnosis of a child with lymphadenopathy, splenomegaly, and cytopenias; obtain discriminating screening laboratory biomarkers, such as serum vitamin B-12 and ferritin levels; and, in the setting of a highly suspicious clinical scenario for ALPS, pursue testing for somatic FAS mutations when germ-line mutation testing is negative. PMID:24101757

Rudman Spergel, Amanda; Walkovich, Kelly; Price, Susan; Niemela, Julie E.; Wright, Dowain; Fleisher, Thomas A.

2013-01-01

225

Is narcolepsy a classical autoimmune disease?  

PubMed

Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness. It is caused by the loss of orexin producing neurons in the lateral hypothalamus. Current evidences suggest an autoimmune mediated process causing the specific loss of orexin neurons. The high association of the disease with the HLA DQB1*06:02, as well as the link with environmental factors and are important clues supporting this theory. Recently, the association between the occurrence of the disease and vaccination campaign after the 2009 H1N1 pandemic highlighted the importance to increase the knowledge in the Pandora box of the vaccines. This review discusses the last finding regarding the pathogenesis of the disease and its relationship with the H1N1 vaccines. PMID:25447795

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

2014-10-29

226

Cognitive and affective dysfunctions in autoimmune thyroiditis.  

PubMed

Hashimoto's thyroiditis (HT) is the most frequent cause of hypothyroidism in areas with sufficient iodine intake. While the impact of thyroid function on mood and cognition is well known, only in the recent years, an increasing number of studies report on the association of HT with cognitive and affective disturbances also in the euthyroid state. Recent imaging studies have shown that these impairments are accompanied by altered brain perfusion, in particular, in the frontal lobe and a reduced gray matter density in the left inferior gyrus frontalis. Brain function abnormalities in euthyroid patients with HT may be subtle and only detected by specific testing or even severe as it is the case in the rare neuropsychiatric disorder Hashimoto's encephalopathy (HE). The good response to glucocorticoids in patients with HE indicates an autoimmune origin. In line with this, the cognitive deficits and the high psycho-social burden in euthyroid HT patients without apparent signs of encephalopathy appear to be associated with anti-thyroid peroxidase auto-antibody (TPO Abs) levels. Though in vitro studies showing binding of TPO Abs to human cerebellar astrocytes point to a potential direct role of TPO Abs in the pathogenesis of brain abnormalities in HT patients, TPO Abs may function only as a marker of an autoimmune disorder of the central nervous system. In line with this, anti-central nervous system auto-antibodies (CNS Abs) which are markedly increased in patients with HT disturb myelinogenesis in vitro and, therefore, may impair myelin sheath integrity. In addition, in HT patients, production of monocyte- and T-lymphocyte-derived cytokines is also markedly increased which may negatively affect multiple neurotransmitters and, consequently, diverse brain neurocircuits. PMID:24685840

Leyhe, Thomas; Müssig, Karsten

2014-10-01

227

Emotional Disorders in People with Multiple Sclerosis  

MedlinePLUS

... worsen problems with functioning caused by MS. Emotional disorders also can: • ... be an autoimmune disease that affects the central nervous system (CNS). The CNS consists of the brain and spinal ...

228

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

PubMed Central

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

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

2014-01-01

229

[Auto-immune diseases and cancers. Second part: auto-immune diseases complicating cancers and their treatment].  

PubMed

Autoimmune diseases may reveal or occur during the course of a neoplasia or its treatment. Autoimmune cytopenia, especially haemolytic anaemia, is common in lymphoproliferative disorders such as chronic lymphoid leukemia. The link between cancer and myositis is well established. Dermatomyositis is associated with an increased relative risk of cancer of 3.4 to 4.4. A combination of detection of antibodies against p155 and TEP-computed tomography may be the best approach to ascertain the presence of occult malignancy in patients with dermatomyositis. A cutaneous or a systemic vascularitis may reveal a cancer, most often a haematological malignancy such as hairy cell leukemia. Paraneoplastic polyarthritis have been described in particular with adenocardinoma of the lungs. Underlying neoplasia should be considered in male smokers patients with new onset polyarthritis and poor health status. The prevalence of autoimmune conditions in myelodysplastic syndromes is 10 to 30%. Vasculitis and relapsing polychondritis are the most commonly reported manifestations. Immune manifestations can also be related to treatment. The most common treatment complications are autoimmune haemolytic anaemia with fludarabine and thyroiditis related to interferon and cervical radiotherapy. PMID:25106665

Pasquet, F; Pavic, M; Ninet, J; Hot, A

2014-10-01

230

The interferon-inducible HIN-200 gene family in apoptosis and inflammation: implication for autoimmunity.  

PubMed

The Ifi-200/HIN-200 gene family encodes highly homologous human (IFI16, myeloid cell nuclear differentiation antigen, absent in melanoma 2, and IFIX) and murine proteins (Ifi202a, Ifi202b, Ifi203, Ifi204, Ifi205, and Ifi206), which are induced by type I and II interferons (IFN). These proteins have been described as regulators of cell proliferation and differentiation and, more recently, several reports have suggested their involvement in both apoptotic and inflammatory processes. The relevance of HIN-200 proteins in human disease is beginning to be clarified, and emerging experimental data indicate their role in autoimmunity. Autoimmune disorders are sustained by perpetual activation of inflammatory process and a link between autoimmunity and apoptosis has been clearly established. Moreover, the interferon system is now considered as a key player in autoimmune disorders such as systemic lupus erythemathosus, systemic sclerosis, and Sjögren's syndrome, and it is therefore conceivable to hypothesize that HIN-200 may be among the pivotal mediators of IFN activity in autoimmune disease. In particular, the participation of HIN-200 proteins in apoptosis and inflammation could support their potential role in autoimmunity. PMID:20187706

Mondini, Michele; Costa, Silvia; Sponza, Simone; Gugliesi, Francesca; Gariglio, Marisa; Landolfo, Santo

2010-04-01

231

Epstein-Barr Virus as a Trigger of Autoimmune Liver Diseases  

PubMed Central

The pathogenesis of autoimmune diseases includes a combination of genetic factors and environmental exposures including infectious agents. Infectious triggers are commonly indicated as being involved in the induction of autoimmune disease, with Epstein-Barr virus (EBV) being implicated in several autoimmune disorders. EBV is appealing in the pathogenesis of autoimmune disease, due to its high prevalence worldwide, its persistency throughout life in the host's B lymphocytes, and its ability to alter the host's immune response and to inhibit apoptosis. However, the evidence in support of EBV in the pathogenesis varies among diseases. Autoimmune liver diseases (AiLDs), including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC), have a potential causative link with EBV. The data surrounding EBV and AiLD are scarce. The lack of evidence surrounding EBV in AiLD may also be reflective of the rarity of these conditions. EBV infection has also been linked to other autoimmune conditions, which are often found to be concomitant with AiLD. This paper will critically examine the literature surrounding the link between EBV infection and AiLD development. The current evidence is far from being conclusive of the theory of a link between EBV and AiLD. PMID:22693505

Rigopoulou, Eirini I.; Smyk, Daniel S.; Matthews, Claire E.; Billinis, Charalambos; Burroughs, Andrew K.; Lenzi, Marco; Bogdanos, Dimitrios P.

2012-01-01

232

The Dual Association between Lymphoma and Autoimmunity  

Microsoft Academic Search

ABSTRACTAutoimmune rheumatic diseases and lymphocytic malignancies are related and this association is bidirectional. Lymphomas occur more frequently in the course of autoimmune disease and autoimmune rheumatic manifestations occur in the course of lymphocytic malignancies. An increased incidence of malignant lymphocytic diseases is present in patients with rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and autoimmune thyroid disease. Descriptions of lymphocytic

M. Ehrenfeld; M. Abu-Shakra; D. Buskila; Y. Shoenfeld

2001-01-01

233

Autoimmunity and antigenic targets in ovarian pathology  

Microsoft Academic Search

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

2004-01-01

234

Anticytotoxic T-Lymphocyte Antigen-4 Induced Autoimmune Hypophysitis: A Case Report and Literature Review  

PubMed Central

Objective. We describe a case of autoimmune hypophysitis induced by the anticytotoxic T-lymphocyte antigen-4 (CTLA-4) agent, ipilimumab. Methods. Case presentation and review of the literature. Results. Autoimmune hypophysitis, a previously described rare disorder, is being recognized more frequently as a side effect of novel immunomodulatory agents used in the treatment of malignancies such as melanoma. CTLA-4 agents are associated with immune-related adverse effects (irAE) which occur as a result of activation (or lack of inactivation) of the immune response. This impacts not only malignant cells but also different host organ-systems. Autoimmune hypophysitis is one of several endocrinopathies associated with these agents. Conclusion. It is important that endocrinologists become familiar with the endocrinopathies, such as autoimmune hypophysitis, associated with new immunomodulator agents which are being used with increasing frequency to treat a variety of malignancies.

Korytkowski, Mary T.

2015-01-01

235

Potential roles of Activation-Induced cytidine Deaminase in promotion or prevention of autoimmunity in humans  

PubMed Central

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. PMID:23215867

Durandy, Anne; Cantaert, Tineke; Kracker, Sven; Meffre, Eric

2014-01-01

236

[Autoimmune pancreatitis in a patient with ulcerative colitis simulating a pancreatic tumor].  

PubMed

Pancreatic endocrine and/or exocrine functional disorders can be commonly detected in patients with inflammatory bowel diseases. Autoimmune pancreatitis is a rare disease and its co-existence with inflammatory bowel disease has been rarely reported. The diagnosis of autoimmune pancreatitis is difficult due to variable nonspecific symptoms, and the high rate of asymptomatic cases. The conventional imaging scans (ultrasonography, computed tomography, retrograde cholangiography) are usually not sensitive enough and they are frequently not able to differentiate between inflammatory and malignant tumorous diseases of the pancreas. The authors present the case history of a patient who developed both ulcerative colitis and autoimmune pancreatitis. The morphological changes of the pancreas detected by ultrasonography suggested the presence of pancreatic cancer, and this diagnosis was supported by the elevated level of serum CA19-9. Computed tomography failed to identify abnormalities in the pancreas and, finally, endoscopic ultrasound combined with fine needle aspiration cytology confirmed the diagnosis of autoimmune pancreatitis. PMID:24936576

Bor, Renáta; Farkas, Klaudia; Bálint, Anita; Wittmann, Tibor; Nagy, Ferenc; Tiszlavicz, László; Molnár, Tamás; Szepes, Zoltán

2014-06-22

237

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

PubMed Central

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

2011-01-01

238

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

PubMed Central

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

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

2014-01-01

239

Autoimmune diseases in Turner syndrome  

Microsoft Academic Search

It has been known that females with Turner syndrome (TS) have an increased prevalence of autoantibodies and are at increased risk of developing autoimmune diseases. Immunological disturbances have been described in TS: a slight decrease in immunoglobulin serum levels and in circulating T and B cells percentages. This data is not entirely in concordance with some more recent studies. The

L. Mazzanti; R. W. Naeraa

2006-01-01

240

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

PubMed Central

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

Galipeau, Jacques; Nooka, Ajay K.

2013-01-01

241

Are there environmental forms of systemic autoimmune diseases?  

PubMed Central

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

Hess, E V

1999-01-01

242

Autoimmunity at the ocular surface: pathogenesis and regulation  

PubMed Central

A healthy ocular surface environment is essential to preserve visual function, and as such the eye has evolved a complex network of mechanisms to maintain homeostasis. Fundamental to the health of the ocular surface is the immune system, designed to respond rapidly to environmental and microbial insults, whereas maintaining tolerance to self-antigens and commensal microbes. To this end, activation of the innate and adaptive immune response is tightly regulated to limit bystander tissue damage. However, aberrant activation of the immune system can result in autoimmunity to self-antigens localized to the ocular surface and associated tissues. Environmental, microbial and endogenous stress, antigen localization, and genetic factors provide the triggers underlying the immunological events that shape the outcome of the diverse spectrum of autoimmune-based ocular surface disorders. PMID:20485329

Stern, ME; Schaumburg, CS; Dana, R; Calonge, M; Niederkorn, JY; Pflufelder, SC

2013-01-01

243

Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity  

PubMed Central

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

Meriggioli, Matthew N; Sanders, Donald B

2009-01-01

244

Novel associations for hypothyroidism include known autoimmune risk loci.  

PubMed

Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the current largest genome-wide association study of hypothyroidism, in 3,736 cases and 35,546 controls. Hypothyroidism was assessed via web-based questionnaires. We identify five genome-wide significant associations, three of which are well known to be involved in a large spectrum of autoimmune diseases: rs6679677 near PTPN22, rs3184504 in SH2B3, and rs2517532 in the HLA class I region (p-values 2.8·10(-13), 2.6·10(-12), and 1.3·10(-8), respectively). We also report associations with rs4915077 near VAV3 (p-value 7.5·10(-10)) and rs925489 near FOXE1 (p value 2.4·10(-19)). VAV3 is involved in immune function, and FOXE1 and PTPN22 have previously been associated with hypothyroidism. Although the HLA class I region and SH2B3 have previously been linked with a number of autoimmune diseases, this is the first report of their association with thyroid disease. The VAV3 association is also novel. We also show suggestive evidence of association for hypothyroidism with a SNP in the HLA class II region (independent of the other HLA association) as well as SNPs in CAPZB, PDE8B, and CTLA4. CAPZB and PDE8B have been linked to TSH levels and CTLA4 to a variety of autoimmune diseases. These results suggest heterogeneity in the genetic etiology of hypothyroidism, implicating genes involved in both autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top association from each of the five genome-wide significant regions in our study, the relative risk between the highest and lowest deciles of genetic risk is 2.0. PMID:22493691

Eriksson, Nicholas; Tung, Joyce Y; Kiefer, Amy K; Hinds, David A; Francke, Uta; Mountain, Joanna L; Do, Chuong B

2012-01-01

245

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

PubMed

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

2014-08-01

246

Narcolepsy, 2009 A(H1N1) pandemic influenza, and pandemic influenza vaccinations: what is known and unknown about the neurological disorder, the role for autoimmunity, and vaccine adjuvants.  

PubMed

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

2014-05-01

247

Autoimmune disease in mothers with the FMR1 premutation is associated with seizures in their children with fragile X syndrome  

PubMed Central

An increased prevalence of autoimmune diseases in family members of children with autism spectrum disorders (ASD) has been previously reported. ASD is also a common problem co-occurring in children with fragile X syndrome (FXS). Why ASD occurs in some individuals with FXS, but not all, is largely unknown. Furthermore, in premutation carrier mothers, there is an increased risk for autoimmune diseases. This study compared the rate of ASD and other neurodevelopmental/behavioral problems in 61 children with FXS born to 41 carrier mothers who had autoimmune disease and in 97 children with FXS of 78 carrier mothers who did not have autoimmune disease. There were no significant differences in the mean age (9.61 ± 5.59 vs. 9.41 ± 6.31, P = 0.836), cognitive and adaptive functioning in children of mothers with and without autoimmune disease. Among children whose mothers had autoimmune disease, the odds ratio (OR) for ASD was 1.27 (95% CI 0.62–2.61, P = 0.5115). Interestingly, the OR for seizures and tics was 3.81 (95% CI 1.13–12.86, P = 0.031) and 2.94 (95% CI 1.19–7.24, P = 0.019), respectively, in children of mothers with autoimmune disease compared to children of mothers without autoimmune disease. In conclusion, autoimmune disease in carrier mothers was not associated with the presence of ASD in their children. However, seizures and tics were significantly increased in children of mothers with autoimmune disease. This suggests a potential new mechanism of seizure and tic exacerbation in FXS related to an intergenerational influence from autoimmunity in the carrier mother. PMID:20809278

Chonchaiya, Weerasak; Tassone, Flora; Ashwood, Paul; Hessl, David; Schneider, Andrea; Campos, Luis; Nguyen, Danh V.

2010-01-01

248

Animal Models of Autoimmune Neuropathy  

PubMed Central

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

Soliven, Betty

2014-01-01

249

Epigenetic alterations and autoimmune disease.  

PubMed

Recent advances in epigenetics have enhanced our knowledge of how environmental factors (UV radiation, drugs, infections, etc.) contribute to the development of autoimmune diseases (AID) in genetically predisposed individuals. Studies conducted in monozygotic twins discordant for AID and spontaneous autoimmune animal models have highlighted the importance of DNA methylation changes and histone modifications. Alterations in the epigenetic pattern seem to be cell specific, as CD4+ T cells and B cells are dysregulated in systemic lupus erythematosus, synovial fibroblasts in rheumatoid arthritis and cerebral cells in multiple sclerosis. With regard to lymphocytes, the control of tolerance is affected, leading to the development of autoreactive cells. Other epigenetic processes, such as the newly described miRNAs, and post-translational protein modifications may also be suspected. Altogether, a conceptual revolution is in progress, in AID, with potential new therapeutic strategies targeting epigenetic patterns. PMID:25141262

Renaudineau, Y; Beauvillard, D; Padelli, M; Brooks, W H; Youinou, P

2011-10-01

250

Infections and Autoimmunity: A Panorama  

Microsoft Academic Search

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

2008-01-01

251

Current therapy for autoimmune hepatitis  

Microsoft Academic Search

The treatment of autoimmune hepatitis is evolving as the pathogenic pathways that underlie the disease are defined, new immunosuppressive agents are tested, and site-specific molecular interventions become feasible. Prednisone alone or at a reduced dose combined with azathioprine is the conventional treatment. Patients with HLA genotype DRB1*0301 have a poorer treatment response and a more frequent need for liver transplantation

Aldo J Montano Loza; Albert J Czaja

2007-01-01

252

Auto-Immunity & Inflammation | ABSTRACTS The expression and role of KLF4 in psoriasis  

E-print Network

Auto-Immunity & Inflammation | ABSTRACTS 097 The expression and role of KLF4 in psoriasis K Kim, H, as measured by RT-PCR, was increased after the treatment of the psoriasis skin and the proliferation of Ha disorders, includ- ing psoriasis. 099 Inflammatory gammadelta T cells collaborate with Th17 cells

Cai, Long

253

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

PubMed

Autoimmune hemolytic anemia is a rare disorder. A 34-year old woman presented with thrombophlebitis after her first delivery, during puerperium. A high titer of cold agglutinins was found. Lymphomas, systemic lupus erythematosus, and tumors were excluded. She conceived again. Due to the anemia she had frequent blood transfusions and she delivered at 38 weeks of gestation. PMID:16854701

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

2006-04-01

254

CELL-MEDIATED IMMUNITY AND INTERFERON GAMMA IN AUTOIMMUNE VITILIGO OF SMYTH LINE CHICKENS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Vitiligo is a common acquired hypopigmentary disorder characterized by a loss of epidermal pigment cells (melanocytes). The Smyth line (SL) chicken is the only animal model for autoimmune vitiligo that recapitulates the entire spectrum of clinical and biological manifestations of the human disease....

255

Autoimmune autonomic ganglionopathy with Sjögren's syndrome: Significance of ganglionic acetylcholine receptor antibody and therapeutic approach  

Microsoft Academic Search

Autoimmune autonomic ganglionopathy (AAG) is a disorder defined by antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia. We report two patients with chronically progressing dysautonomia with Sjögren's syndrome (SS). The first case showed elevated titer of ganglionic acetylcholine receptor (AChR) antibody and improved with oral intake of prednisolone. In contrast, the second case showed no elevation of ganglionic

Takayuki Kondo; Haruhisa Inoue; Takashi Usui; Tsuneyo Mimori; Hidekazu Tomimoto; Steven Vernino; Ryosuke Takahashi

2009-01-01

256

Personality disorders  

MedlinePLUS

... personality disorder Histrionic personality disorder Narcissistic personality disorder Obsessive-compulsive personality disorder Paranoid personality disorder Schizoid personality disorder Schizotypal personality disorder

257

Genetic association, seasonal infections and autoimmune basis of narcolepsy  

PubMed Central

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

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

2014-01-01

258

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

PubMed Central

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

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

1999-01-01

259

Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations.  

PubMed

Germline loss-of-function mutations in the transcription factor signal transducer and activator of transcription 3 (STAT3) cause immunodeficiency, whereas somatic gain-of-function mutations in STAT3 are associated with large granular lymphocytic leukemic, myelodysplastic syndrome, and aplastic anemia. Recently, germline mutations in STAT3 have also been associated with autoimmune disease. Here, we report on 13 individuals from 10 families with lymphoproliferation and early-onset solid-organ autoimmunity associated with 9 different germline heterozygous mutations in STAT3. Patients exhibited a variety of clinical features, with most having lymphadenopathy, autoimmune cytopenias, multiorgan autoimmunity (lung, gastrointestinal, hepatic, and/or endocrine dysfunction), infections, and short stature. Functional analyses demonstrate that these mutations confer a gain-of-function in STAT3 leading to secondary defects in STAT5 and STAT1 phosphorylation and the regulatory T-cell compartment. Treatment targeting a cytokine pathway that signals through STAT3 led to clinical improvement in 1 patient, suggesting a potential therapeutic option for such patients. These results suggest that there is a broad range of autoimmunity caused by germline STAT3 gain-of-function mutations, and that hematologic autoimmunity is a major component of this newly described disorder. Some patients for this study were enrolled in a trial registered at www.clinicaltrials.gov as #NCT00001350. PMID:25359994

Milner, Joshua D; Vogel, Tiphanie P; Forbes, Lisa; Ma, Chi A; Stray-Pedersen, Asbjřrg; Niemela, Julie E; Lyons, Jonathan J; Engelhardt, Karin R; Zhang, Yu; Topcagic, Nermina; Roberson, Elisha D O; Matthews, Helen; Verbsky, James W; Dasu, Trivikram; Vargas-Hernandez, Alexander; Varghese, Nidhy; McClain, Kenneth L; Karam, Lina B; Nahmod, Karen; Makedonas, George; Mace, Emily M; Sorte, Hanne S; Perminow, Gřri; Rao, V Koneti; O'Connell, Michael P; Price, Susan; Su, Helen C; Butrick, Morgan; McElwee, Joshua; Hughes, Jason D; Willet, Joseph; Swan, David; Xu, Yaobo; Santibanez-Koref, Mauro; Slowik, Voytek; Dinwiddie, Darrell L; Ciaccio, Christina E; Saunders, Carol J; Septer, Seth; Kingsmore, Stephen F; White, Andrew J; Cant, Andrew J; Hambleton, Sophie; Cooper, Megan A

2015-01-22

260

Spontaneous autoimmunity prevented by thymic expression of a single self-antigen  

PubMed Central

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. PMID:17116738

DeVoss, Jason; Hou, Yafei; Johannes, Kellsey; Lu, Wen; Liou, Gregory I.; Rinn, John; Chang, Howard; Caspi, Rachel; Fong, Lawrence; Anderson, Mark S.

2006-01-01

261

The role of dendritic cells in autoimmunity  

PubMed Central

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

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

2014-01-01

262

Autoimmune and Neoplastic Thyroid Diseases Associated with Hepatitis C Chronic Infection  

PubMed Central

Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender versus healthy controls, or hepatitis B virus infected patients. In patients with “HCV-associated mixed cryoglobulinemia” (MC + HCV), a higher prevalence of thyroid autoimmune disorders was shown not only compared to controls, but also versus HCV patients without cryoglobulinemia. Patients with MC + HCV or HCV chronic infection show a higher prevalence of papillary thyroid cancer than controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC + HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine, but normal levels of Th2 (C-C motif) ligand 2 chemokine, than patients without thyroiditis. HCV thyroid infection could act by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes that secrete interferon-? and tumor necrosis factor-?. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, which may lead to the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function, particularly where nodules occur, is recommended in HCV patients. PMID:25374602

Fallahi, Poupak; Ferrari, Silvia Martina; Politti, Ugo; Giuggioli, Dilia; Ferri, Clodoveo

2014-01-01

263

Autoimmune and neoplastic thyroid diseases associated with hepatitis C chronic infection.  

PubMed

Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender versus healthy controls, or hepatitis B virus infected patients. In patients with "HCV-associated mixed cryoglobulinemia" (MC + HCV), a higher prevalence of thyroid autoimmune disorders was shown not only compared to controls, but also versus HCV patients without cryoglobulinemia. Patients with MC + HCV or HCV chronic infection show a higher prevalence of papillary thyroid cancer than controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC + HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine, but normal levels of Th2 (C-C motif) ligand 2 chemokine, than patients without thyroiditis. HCV thyroid infection could act by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes that secrete interferon-? and tumor necrosis factor-?. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, which may lead to the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function, particularly where nodules occur, is recommended in HCV patients. PMID:25374602

Fallahi, Poupak; Ferrari, Silvia Martina; Politti, Ugo; Giuggioli, Dilia; Ferri, Clodoveo; Antonelli, Alessandro

2014-01-01

264

Environmental factors producing autoimmune dysregulation--chronic activation of T cells caused by silica exposure.  

PubMed

Autoimmune disorders are induced by various environmental and occupational substances. Among the most typical factors involving these substances, it is well known that silica exposure causes not only pulmonary fibrosis known as silicosis, but also induces autoimmune diseases such as rheumatoid arthritis known as Caplan's syndrome, systemic sclerosis, systemic lupus erythematosus, and anti-neutrophil cytoplasmic autoantibody (ANCA)-related vasculitis/nephritis. To investigate the immunological effects of silica, a focus on the occurrence of autoimmune dysfunction may clarify these autoimmune diseases and develop effective tools for observing silicosis patients (SIL). In this review, our investigation concerns the autoantibodies found in SIL, alteration of CD95/Fas and related molecules in SIL, case-oriented and in vitro analyses of silica-induced activation of responder and regulatory T cells, and supposed mechanisms of reduction of CD4+25+FoxP3+ regulatory T cells (T(reg)) in SIL. Further studies are required to investigate Th17 and the interaction with T(reg) in SIL to understand the cellular and molecular mechanisms of environmental and occupational autoimmune disorders. PMID:22226303

Lee, Suni; Hayashi, Hiroaki; Maeda, Megumi; Chen, Ying; Matsuzaki, Hidenori; Takei-Kumagai, Naoko; Nishimura, Yasumitsu; Fujimoto, Wataru; Otsuki, Takemi

2012-07-01

265

Lectins, agglutinins, and their roles in autoimmune reactivities.  

PubMed

Lectins are carbohydrate-binding proteins present throughout nature that act as agglutinins. Approximately 30% of our food contains lectins, some of which may be resistant enough to digestion to enter the circulation. Because of their binding properties, lectins can cause nutrient deficiencies, disrupt digestion, and cause severe intestinal damage when consumed in excess by an individual with dysfunctional enzymes. These effects are followed by disruption of intestinal barrier integrity, which is the gateway to various autoimmunities. Shared amino acid motifs between dietary lectins, exogenous peptides, and various body tissues may lead to cross-reactivity, resulting in the production of antibodies against lectin and bacterial antigens, followed by autoimmunity. The detection of immunoglobulin G (IgG) or immunoglobulin A (IgA) antibodies against specific lectins may serve as a guide for the elimination of these lectins from the diet. It is proposed that this process can reduce the peripheral antigenic stimulus and, thereby, result in a diminution of disease symptoms in some-but not all-patients with autoimmune disorders. PMID:25599185

Vojdani, Aristo

2015-01-01

266

Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1.  

PubMed

Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies (Aabs) toward intracellular enzymes are a hallmark for APS1 and serve as diagnostic markers and predictors for disease manifestations. In this study, we aimed to identify pituitary autoantigens in patients with APS1. A pituitary cDNA expression library was screened with APS1 sera and a tudor domain containing protein 6 (TDRD6) cDNA clone was isolated. Positive immunoreactivity against in vitro translated TDRD6 fragments was shown in 42/86 (49%) APS1 patients but not in patients with other autoimmune diseases or in healthy controls. By using immunohistochemistry, sera from 3/6 APS1 patients with growth hormone (GH) deficiency showed immunostaining of a small number of guinea pig anterior pituitary cells, and 40-50% of these cells were GH-positive. No such immunostaining was seen with sera from healthy controls. The APS1 Aab-positive, GH-negative cells may represent a novel subpopulation of anterior pituitary cells. In addition, 4/6 patient sera showed staining of a fiber-plexus in the pituitary intermediate lobe recognizing enzymes of monoamine and GABA synthesis. Thus, we have identified TDRD6 as a major autoantigen in APS1 patients and shown that several sera from GH-deficient patients stain specific cell populations and nerves in the pituitary gland. PMID:17215373

Bensing, Sophie; Fetissov, Sergueď O; Mulder, Jan; Perheentupa, Jaakko; Gustafsson, Jan; Husebye, Eystein S; Oscarson, Mikael; Ekwall, Olov; Crock, Patricia A; Hökfelt, Tomas; Hulting, Anna-Lena; Kämpe, Olle

2007-01-16

267

Journal of Autoimmune Diseases BioMed Central Hypothesis  

E-print Network

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. DilantinTreatmentMelanocyteImmunityCytokines Vitiligo is a psychologically devastating clinical conundrum which affects approximately 1 % of the general population. The exact cause of the illness is an enigma, but several hypotheses about its pathogenesis are advanced. The autoimmune hypothesis proposes an autoimmune attack against melanocytes. Although anti-melanocyte autoantibodies have been demonstrated in vitiligo, recent research casts doubt on their pathogenic role and instead supports the involvement of cell-mediated autoimmune response in the pathobiology of this disorder, which is characterized by increase of suppressor T-cells and decrease of the helper/suppressor ratio in association with the presence of type-1 cytokine secreting cytotoxic T cells in the vicinity of disappearing melanocytes. The neural hypothesis proposes that increased release of norepinephrine, a melanocytotoxin, from the autonomic nerve endings in the microenvironment of melanocytes injures these cells. Moreover, norepinephrine induces the catecholamine degrading enzyme monoamine oxidase (MAO), which favors the formation of toxic levels of hydrogen peroxide in the vicinity of melanocytes.

Mr Namazi

2005-01-01

268

Inflammasome activation in obesity-related inflammatory diseases and autoimmunity  

PubMed Central

The inflammasome is a highly regulated protein complex that triggers caspase-1 activation and subsequent secretion of IL-1? and IL-18. Recognition of microbial components and danger signals by NOD-like receptor (NLR) family members in the cytosol promotes inflammasome activation and downstream inflammatory cytokine production. Pathogen recognition by NLRs and downstream release of inflammasome-derived cytokines are important in host defense against numerous infections. Recent studies have also identified a unique role for inflammasome regulation in the induction and pathogenesis of multiple autoimmune and inflammatory disorders. We now know that obesity-related factors and endogenous markers of cellular stress can lead to unchecked activation of the inflammasome and provoke inflammation and subsequent destruction of vital organs. This review will highlight recent findings that link inflammasome signaling to the progression of autoinflammatory and autoimmune diseases. We will focus on the contribution of inflammasome activation to the pathogenesis of autoinflammatory and autoimmune diseases that are of major significance to human health including type 2 diabetes, atherosclerosis, multiple sclerosis and type 1 diabetes. PMID:21794210

Lukens, John; Dixit, Vishwa Deep; Kanneganti, Thirumala-Devi

2014-01-01

269

Gender disparities in ocular inflammatory disorders*.  

PubMed

Abstract Ocular inflammatory disorders disproportionately affect women, and the majority of affected women are of childbearing age. The role of sex or reproductive hormones has been proposed in many other inflammatory or autoimmune disorders, and findings from non-ocular autoimmune diseases suggest a complex interaction between sex hormones, genetic factors and the immune system. However, despite the age and sex bias, factors that influence this disparity are complicated and unclear. This review aims to evaluate the gender disparities in prevalence, incidence and severity of the most common infectious and non-infectious ocular inflammatory disorders. PMID:24987987

Sen, Hatice Nida; Davis, Janet; Ucar, Didar; Fox, Austin; Chan, Chi Chao; Goldstein, Debra A

2015-02-01

270

Gender Disparities in Ocular Inflammatory Disorders*  

PubMed Central

Ocular inflammatory disorders disproportionately affect women, and the majority of affected women are of childbearing age. The role of sex or reproductive hormones has been proposed in many other inflammatory or autoimmune disorders, and findings from non-ocular autoimmune diseases suggest a complex interaction between sex hormones, genetic factors and the immune system. However, despite the age and sex bias, factors that influence this disparity are complicated and unclear. This review aims to evaluate the gender disparities in prevalence, incidence and severity of the most common infectious and non-infectious ocular inflammatory disorders. PMID:24987987

Sen, Hatice Nida; Davis, Janet; Ucar, Didar; Fox, Austin; Chan, Chi Chao; Goldstein, Debra A.

2014-01-01

271

Autoimmune autonomic ganglionopathy with reversible cognitive impairment  

PubMed Central

Background Autoimmune autonomic ganglionopathy (AAG) is a rare disorder of antibody mediated impaired transmission across the autonomic ganglia resulting in severe autonomic failure. Some patients with AAG report cognitive impairment of unclear etiology despite treatment of autonomic symptoms. Objectives To investigate the relationship between orthostatic hypotension, antibody titers and cognitive impairment in patients with AAG. Design Prospective cohort. Setting Academic medical center. Participants Three patients with AAG underwent neuropsychological testing before and after cycles of plasma exchange in both the seated and standing position to determine the effects of orthostatic hypotension and antibody titers on cognition. Main Outcome Measures Patient responses to neuropsychological tests were measured by percent change from baseline in the seated and standing positions pre- and post-plasma exchange to determine the effects of orthostatic hypotension and antibody titers on cognition. Results Orthostatic hypotension and elevated antibody titer were associated independently with neuropsychological impairment (P<0.05), particularly in domains of executive function, sustained attention, and working memory. Cognitive dysfunction improved, even in the seated normotensive position, after plasmapheresis and consequent reduction in antibody levels. Conclusion The data presented in this study demonstrate reversible cognitive impairment is independently associated with both orthostatic hypotension and elevated nicotinic acetylcholine receptor autoantibodies thereby expanding the clinical spectrum of autonomic ganglionopathy and, in so doing, providing an additional treatable cause of cognitive impairment. PMID:22158721

Gibbons, Christopher H.; Centi, Justin; Vernino, Steven; Freeman, Roy

2012-01-01

272

Idiopathic bilateral vestibulopathy: an autoimmune disease?  

PubMed

Bilateral vestibulopathy (BV) is the loss of function of both peripheral labyrinths or of the eighth nerves. Its etiology remains obscure in approximately 20% to 50% of cases (so-called idiopathic bilateral vestibulopathy, IBV). Alternatively, the cause could be viral or vascular; to date, causative gene mutations have not been identified. Other potential disease mechanisms include autoimmune disorders. Antibodies have been detected against inner ear tissue (primarily against vestibular membranous labyrinth). The data suggest that the bulk of anti-labyrinthine autoantibodies may be an epiphenomenon, but a small subgroup of organ-specific autoantibodies may synergize with a cellular response to develop vestibular lesions. The two key symptoms of BV are the following: 1. unsteadiness of gait, particularly in the dark or on uneven ground, and 2. oscillopsia associated with head movements. Episodes of vertigo are reported by patients with IBV, particularly early in the development of vestibular loss. Associated hearing loss seldom occurs in the idiopathic type of this condition. Post-mortem examinations revealed a remarkably selective loss of vestibular hair cells in the vestibular end organs but normal hair cells in the cochlea. The diagnosis is made with a simple bedside test for defective vestibular function. The diagnosis can be confirmed by bithermal caloric testing and pendular body rotation. The therapy is based on steroid treatment, and the early initiation of immunosuppression appears to be essential for therapeutic success. PMID:25173622

Greco, Antonio; De Virgilio, Armando; Gallo, Andrea; Fusconi, Massimo; Ruoppolo, Giovanni; Turchetta, Rosaria; Pagliuca, Giulio; de Vincentiis, Marco

2014-10-01

273

Autoimmune Dysregulation and Purine Metabolism in Adenosine Deaminase Deficiency  

PubMed Central

Genetic defects in the adenosine deaminase (ADA) gene are among the most common causes for severe combined immunodeficiency (SCID). ADA-SCID patients suffer from lymphopenia, severely impaired cellular and humoral immunity, failure to thrive, and recurrent infections. Currently available therapeutic options for this otherwise fatal disorder include bone marrow transplantation (BMT), enzyme replacement therapy with bovine ADA (PEG-ADA), or hematopoietic stem cell gene therapy (HSC-GT). Although varying degrees of immune reconstitution can be achieved by these treatments, breakdown of tolerance is a major concern in ADA-SCID. Immune dysregulation such as autoimmune hypothyroidism, diabetes mellitus, hemolytic anemia, and immune thrombocytopenia are frequently observed in milder forms of the disease. However, several reports document similar complications also in patients on long-term PEG-ADA and after BMT or GT treatment. A skewed repertoire and decreased immune functions have been implicated in autoimmunity observed in certain B-cell and/or T-cell immunodeficiencies, but it remains unclear to what extent specific mechanisms of tolerance are affected in ADA deficiency. Herein we provide an overview about ADA-SCID and the autoimmune manifestations reported in these patients before and after treatment. We also assess the value of the ADA-deficient mouse model as a useful tool to study both immune and metabolic disease mechanisms. With focus on regulatory T- and B-cells we discuss the lymphocyte subpopulations particularly prone to contribute to the loss of self-tolerance and onset of autoimmunity in ADA deficiency. Moreover we address which aspects of immune dysregulation are specifically related to alterations in purine metabolism caused by the lack of ADA and the subsequent accumulation of metabolites with immunomodulatory properties. PMID:22969765

Sauer, Aisha Vanessa; Brigida, Immacolata; Carriglio, Nicola; Aiuti, Alessandro

2012-01-01

274

Association between autoimmune pancreatitis and systemic autoimmune diseases  

PubMed Central

AIM: To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4). METHODS: The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment. Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and, in some cases, by computer tomography (CT). RESULTS: Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients. 10 patients had Sjögren’s syndrome (SS) (IgG4: 590 ± 232 mg/L), 2 of them in association with Hashimoto’s thyroiditis, and 7 patients (IgG4: 1388 ± 985.5 mg/L) had systemic lupus erythematosus (SLE). The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L). Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level. CONCLUSION: The serum IgG4 level may be elevated in SAIDs without the presence of AIP. The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs. PMID:22690073

Terzin, Viktória; Földesi, Imre; Kovács, László; Pokorny, Gyula; Wittmann, Tibor; Czakó, László

2012-01-01

275

ORIGINAL ARTICLE Toward defining the autoimmune microbiome  

E-print Network

U N C O R R EC TED PR O O F ORIGINAL ARTICLE Toward defining the autoimmune microbiome for type 1 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

Casella, George

276

Multiple sclerosis: a complicated picture of autoimmunity  

Microsoft Academic Search

Understanding of autoimmune diseases, including multiple sclerosis, has expanded considerably in recent years. New insights have been provided by not only animal models but also studies of patients, often in conjunction with experimental therapies. It is accepted that autoimmune T cells mediate the early steps of new multiple sclerosis lesions, and although uncertainties remain about the specific targets of autoreactive

Roland Martin; Henry F McFarland

2007-01-01

277

Macrophage Activation Syndrome in Autoimmune Disease  

Microsoft Academic Search

Macrophage activation syndrome (MAS) is a phenomenon characterized by cytopenia, organ dysfunction, and coagulopathy associated with an inappropriate activation of macrophages. Current diagnostic criteria are imprecise, but the syndrome is now recognized as a form of hemophagocytic lymphohistiocytosis that is characteristically associated with autoimmune diatheses. The diagnosis of incipient MAS in patients with autoimmune disease requires a high index of

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

2010-01-01

278

Mental Disorders  

MedlinePLUS

... disorder, and phobias Bipolar disorder Depression Mood disorders Personality disorders Psychotic disorders, including schizophrenia There are many causes of mental disorders. Your genes and family history ...

279

[Autoimmune thrombocitopenic purpura in pregnancy].  

PubMed

The author deals with haematologists' and obstetricians' current views on acquired ATP in children and adults, characterised by a transient, acute or chronic decrease in platelets count (<50.109/l) due to premature destruction by the reticuloendothelial system. The most common questions arising in connection with this disease are: what is autoimmune thrombocytopenic purpura; is there any correlation between pregnancy and ATP; what are its symptoms; does pregnancy itself affect the autoimmune disease. If is of utter importance for women with ATP to be aware of the risks these symptoms pose both on the health of the mother and the foetus. Obstetricians and gynaecologists seldom object to pregnancy in women with ATP. Nevertheless, it is essential to point out that additional monitoring and therapy are needed. There is no medical evidence that supports the notion of terminating pregnancy due to ATP. Assessment is made only by an obstetrician, haematologist and pediatrician working in close collaboration. This collaborative work must be present throughout the whole pregnancy, delivery and puerperium. The treatment necessary for women with ATP aims to establish platelet count over 50.000 ppm when approaching the end of pregnancy, preferably between 80.000 ppm - 100.000 ppm taking into account vagina or surgical delivery as well as the administration of anaesthetic. Delivery management must be decided entirely on obstetrics consideration, but not on ATP ones. Pregnant women with ATP must be monitored and treated with caution by a highly specialised medical team. PMID:20225496

Christova, R; Lisichkov, T; Chernev, T

2009-01-01

280

Recurrent pericarditis: infectious or autoimmune?  

PubMed

The etiology and pathogenesis of idiopathic recurrent acute pericarditis (IRAP) remain controversial standing like a bridge that crosses infectious, autoimmune and autoinflammatory pathways. Anything may cause acute pericarditis; Echo-virus, and Coxsackie are the most frequently involved viruses, Mycobacterium tuberculosis and Coxiella burnetii the most common bacteria, but in 85% of cases it remains "idiopathic". Recurrences occur in up to 20-50% of patients. An immuno-mediated pathogenesis is suggested by the presence of pro-inflammatory cytokines in pericardial fluid, the presence of antinuclear autoantibodies (ANA) in sera of the patients, the occurrence of new autoimmune diagnoses and the good response to anti-inflammatory or immunosuppressive therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) must be used at recommended dosages, till the resolution of symptoms and normalization of C-reactive protein and erythrocyte sedimentation rate. Corticosteroids should be used rarely, at low doses, with an extremely low tapering and with osteoporosis prevention. Colchicine leads to a clinically important and statistically significant benefit, reducing recurrences by 50%. The long term outcome of IRAP is good, without evidence of constriction even after a very long follow-up. PMID:18708165

Brucato, Antonio; Maestroni, Silvia; Cumetti, Davide; Thiella, Giuseppe; Alari, Gabriella; Brambilla, Giovanni; Imazio, Massimo; Doria, Andrea; Palmieri, Giancarlo; Adler, Yehuda

2008-10-01

281

Cardiovascular Involvement in Autoimmune Diseases  

PubMed Central

Autoimmune diseases (AD) represent a broad spectrum of chronic conditions that may afflict specific target organs or multiple systems with a significant burden on quality of life. These conditions have common mechanisms including genetic and epigenetics factors, gender disparity, environmental triggers, pathophysiological abnormalities, and certain subphenotypes. Atherosclerosis (AT) was once considered to be a degenerative disease that was an inevitable consequence of aging. However, research in the last three decades has shown that AT is not degenerative or inevitable. It is an autoimmune-inflammatory disease associated with infectious and inflammatory factors characterized by lipoprotein metabolism alteration that leads to immune system activation with the consequent proliferation of smooth muscle cells, narrowing arteries, and atheroma formation. Both humoral and cellular immune mechanisms have been proposed to participate in the onset and progression of AT. Several risk factors, known as classic risk factors, have been described. Interestingly, the excessive cardiovascular events observed in patients with ADs are not fully explained by these factors. Several novel risk factors contribute to the development of premature vascular damage. In this review, we discuss our current understanding of how traditional and nontraditional risk factors contribute to pathogenesis of CVD in AD. PMID:25177690

Amaya-Amaya, Jenny

2014-01-01

282

Telomere dysfunction, autoimmunity and aging.  

PubMed

Immune aging is associated with loss of critical immune functions, such as host protection from infection and malignancy. Unexpectedly, immunosenescence also renders the host susceptible to inflammation, which may translate into tissue-damaging disease as the senescent immune system loses its ability to maximize inflammatory protection while minimizing inflammatory injury. On the other hand, chronic inflammation associated with immune-mediated disease represents a profound stress factor for the immune system, affecting cellular turn-over, replication and exhaustion. Immune cell longevity is tightly connected to the functional integrity of telomeres which are regulated by cell multiplication, exposure to oxidative stress and DNA repair mechanisms. Lymphocytes are amongst the few cell types that can actively elongate telomeres through the action of telomerase. In patients with the autoimmune disease rheumatoid arthritis (RA), telomerase deficiency is associated with prematurity of immune aging. Patients with RA have other defects in DNA repair mechanisms, including the kinase Ataxia telangiectasia mutated (ATM), critically involved in the repair of DNA double strand breaks. ATM deficiency in RA shortens lymphocyte survival. Dynamics of telomeric length and structure are beginning to be understood and have distinct patterns in different autoimmune diseases, suggesting a multitude of molecular mechanisms defining the interface between chronic immune stimulation and progressive aging of the immune system. PMID:22396899

Hohensinner, Philipp J; Goronzy, Jörg J; Weyand, Cornelia M

2011-12-01

283

IP-10 in autoimmune thyroiditis.  

PubMed

The interferon-?-inducible protein 10 (IP-10) was initially identified as a chemokine that is induced by interferon (IFN)-?. IP-10 exerts its function through binding to chemokine (C-X-C motif) receptor 3 (CXCR3). IP-10 and its receptor, CXCR3, appear to contribute to the pathogenesis of many autoimmune diseases, organ specific (such as type 1 diabetes, Graves' disease and ophthalmopathy), or systemic (such as systemic lupus erythematosus, mixed cryoglobulinemia, Sjogren syndrome, or systemic sclerosis). The secretion of IP-10 by (CD)4+, CD8+, and natural killer is dependent on IFN-?. Under the influence of IFN-?, IP-10 is secreted by thyrocytes. Determination of high level of IP-10 in peripheral fluids is therefore a marker of a T helper 1 orientated immune response. High levels of circulating IP-10, have been shown in patients with autoimmune thyroiditis (AT). Among patients with AT, IP-10 levels were significantly higher in those with a hypoechoic ultrasonographic pattern, which is a sign of a more severe lympho-monocytic infiltration, and in those with hypothyroidism. For these reasons, it has been postulated that IP-10 could be a marker of a stronger and more aggressive inflammatory response in the thyroid, subsequently leading to thyroid destruction and hypothyroidism. Further studies are needed to investigate whether IP-10 is a novel therapeutic target in AT. PMID:24977661

Ruffilli, I; Ferrari, S M; Colaci, M; Ferri, C; Fallahi, P; Antonelli, A

2014-08-01

284

The autoimmune concept of atherosclerosis  

PubMed Central

Purpose of review This review summarizes the recent data on the ‘Autoimmune Concept of Atherosclerosis’, according to which the first stage of this disease is due to an autoimmune reaction against arterial endothelial cells expressing heat shock protein 60 (HSP60) and adhesion molecules when stressed by classical atherosclerosis risk factors. Special emphasis is put on oxidized low-density lipoproteins as early endothelial stressors. Recent findings Plasma cholesterol and LDL levels considered ‘normal’ by the medical community are possibly too high from an evolutionary viewpoint. The proinflammatory milieu at sites of early atherosclerotic lesions could be conducive to oxidation of LDL in situ. LDL oxidation can also take place at nonvascular sites or in the circulation under general proinflammatory conditions explaining its proatherosclerotic role in ‘normocholesterolemic’ individuals. Summary We hypothesize that the plasma cholesterol and LDL levels currently considered normal are evolutionarily too high. Cholesterol and/or oxidized low-density lipoprotein, even as a mild HSP60-inducing endothelial stressor, function as a ubiquitous risk factor. If this hypothesis is true, most members of developed societies might be at risk to develop atherosclerotic plaques at anti-HSP60-immunity-triggered intimal inflammatory foci, irrespective of the primary risk-factor(s). PMID:21881502

Grundtman, Cecilia; Wick, Georg

2011-01-01

285

T Cell Subsets in Obsessive-Compulsive Disorder  

Microsoft Academic Search

Stress can produce immunosuppression leading to increased susceptibility to infection, tumor growth or autoimmune disease. It has been recently noted, however, that certain kinds of stress need not increase the risk of immune pathology. The present study looked for immune pathology in an anxiety-related disorder. Acute exacerbation of obsessive-compulsive disorder (OCD), an anxiety spectrum disorder, served as a model for

Y. Barber; P. Toren; A. Achiron; S. Noy; L. Wolmer; R. Weizman; N. Laor

1996-01-01

286

Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease  

PubMed Central

The innate immune system utilizes many approaches for defense against invading microorganisms, including complement-mediated lysis, engulfment, formation of neutrophil extracellular traps (NETs) and release of antimicrobial peptides (AMPs). While classically thought to be driven by adaptive immunity, the development of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is increasingly associated with dysregulated innate immune pathways. An emerging theme within this literature is the contribution of AMPs to the development of autoimmune disorders. This is best exemplified in atopic dermatitis and psoriasis where the defensins and the single human cathelicidin, LL-37, may contribute to disease. Further, in the past few years, a role for LL-37 has emerged in the pathogenesis of SLE, RA, atherosclerosis and possibly other diseases. This review discusses the role of LL-37 and its murine ortholog, mCRAMP, in the modulation of immune and inflammatory pathways and their effects on autoimmune and inflammatory diseases. PMID:24185823

Kahlenberg, J. Michelle; Kaplan, Mariana J.

2013-01-01

287

Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS)  

PubMed Central

Summary Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of T cell dysregulation caused by defective Fas-mediated apoptosis. Patients with ALPS can develop a myriad of clinical manifestations including lymphadenopathy, hepatosplenomegaly, autoimmunity and increased rates of malignancy. ALPS may be more common that originally thought, and testing for ALPS should be considered in patients with unexplained lymphadenopathy, hepatosplenomegaly, and/or autoimmunity. As the pathophysiology of ALPS is better characterized, a number of targeted therapies are in preclinical development and clinical trials with promising early results. This review describes the clinical and laboratory manifestations found in ALPS patients, as well as the molecular basis for the disease and new advances in treatment. PMID:19930184

Teachey, David T.; Seif, Alix E.; Grupp, Stephan A.

2010-01-01

288

Beneficial effect of testosterone in the treatment of chronic autoimmune thyroiditis in rats  

SciTech Connect

Early thymectomy and sublethal irradiation of normal rats consistently induces a sex-dependent chronic autoimmune thyroiditis. Females are much more susceptible to this autoimmune disorder than are males. The possible therapeutic effects of testosterone (Te) on established autoimmune thyroiditis has been investigated in this model. The pathologic condition of the gland before treatment was monitored by a thyroid grafting and extirpation techniques. Te administration by either parenteral injection or implantation caused significant regression of established thyroiditis. Repeated doses of Te ester in oil were found to be more effective than powdered free-Te given by implantation, and frequently produced complete resolution of chronic lesions involving the entire gland. In these thyroids, there was reappearance of normal thyroid architecture and complete absence of mononuclear cellular infiltration. However, no inhibitory effect on serum autoantibody production to thyroglobulin was noted with any form of Te treatment. These observations strengthen the concept that cellular rather than humoral mechanisms are involved in the pathogenesis of thyroiditis.

Ahmed, S.A.; Young, P.R.; Penhale, W.J.

1986-01-01

289

A Coincidence of Rheumatoid Arthritis, Autoimmune Thyroid Disease and Vitiligo in a Single Patient: A Possible Pathogenetic Linkage  

PubMed Central

It has been widely observed that disorders with an autoimmune pathogenesis occur with increased frequency in patients with a history of another autoimmune disease (AD). The numbers of documented cases of a co-occurrence of different autoimmune diseases in a single patient in addition to studies investigating the possible common etiopathogenesis of these diseases have increased in recent years. Available data suggest that the presence of one AD should alert the clinician to the possibility of a second AD. In this report, we aimed to draw attention to these potential coincidences and the possible pathogenetic linkages between three distinct ADs in a single individual diagnosed with rheumatoid arthritis, autoimmune thyroid disease and vitiligo. Further documentation of observations of possible coincidence are required in order to yield results that may shed light on the biological pathways of these diseases.

Meliko?lu, Meltem Alkan; Meliko?lu, Mehmet; Karatay, Saliha; U?ur, Mahir; ?enel, Kaz?m

2008-01-01

290

Low-Dose Interleukin-2 Therapy: A Driver of an Imbalance between Immune Tolerance and Autoimmunity  

PubMed Central

For many years, the role of interleukin-2 (IL-2) in autoimmune responses was established as a cytokine possessing strong pro-inflammatory activity. Studies of the past few years have changed our knowledge on IL-2 in autoimmune chronic inflammation, suggesting its protective role, when administered at low-doses. The disrupted balance between regulatory and effector T cells (Tregs and Teffs, respectively) is a characteristic of autoimmune diseases, and is dependent on homeostatic cytokines, including IL-2. Actually, inherent defects in the IL-2 signaling pathway and/or levels leading to Treg compromised function and numbers as well as Th17 expansion have been attributed to autoimmune disorders. In this review, we discuss the role of IL-2 in the pathogenesis of autoimmune diseases. In particular, we highlight the impact of the dysregulated IL-2 pathway on disruption of the Treg/Th17 balance, reversal of which appears to be a possible mechanism of the low-dose IL-2 treatment. The negative effects of IL-2 on the differentiation of follicular helper T cells (Tfh) and pathogenic Th17 cells, both of which contribute to autoimmunity, is emphasized in the paper as well. We also compare the current IL-2-based therapies of animal and human subjects with immune-mediated diseases aimed at boosting the Treg population, which is the most IL-2-dependent cell subset desirable for sufficient control of autoimmunity. New perspectives of therapeutic approaches focused on selective delivery of IL-2 to inflamed tissues, thus allowing local activity of IL-2 to be combined with its reduced systemic and pleiotropic toxicity, are also proposed in this paper. PMID:25322151

Kosmaczewska, Agata

2014-01-01

291

TLR2 and TLR4 in autoimmune diseases: a comprehensive review.  

PubMed

Autoimmune diseases are immune disorders characterized by T cell hyperactivity and B cell overstimulation leading to overproduction of autoantibodies. Although the pathogenesis of various autoimmune diseases remains to be elucidated, environmental factors have been thought to contribute to the initiation and maintenance of auto-respond inflammation. Toll-like receptors (TLRs) are pattern recognition receptors belonging to innate immunity that recognize and defend invading microorganisms. Besides these exogenous pathogen-associated molecular patterns, TLRs can also bind with damage-associated molecular patterns produced under strike or by tissue damage or cells apoptosis. It is believed that TLRs build a bridge between innate immunity and autoimmunity. There are five adaptors to TLRs including MyD88, TRIF, TIRAP/MAL, TRAM, and SARM. Upon activation, TLRs recruit specific adaptors to initiate the downstream signaling pathways leading to the production of inflammatory cytokines and chemokines. Under certain circumstances, ligation of TLRs drives to aberrant activation and unrestricted inflammatory responses, thereby contributing to the perpetuation of inflammation in autoimmune diseases. In the past, most studies focused on the intracellular TLRs, such as TLR3, TLR7, and TLR9, but recent studies reveal that cell surface TLRs, especially TLR2 and TLR4, also play an essential role in the development of autoimmune diseases and afford multiple therapeutic targets. In this review, we summarized the biological characteristics, signaling mechanisms of TLR2/4, the negative regulators of TLR2/4 pathway, and the pivotal function of TLR2/4 in the pathogenesis of autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, psoriasis, multiple sclerosis, and autoimmune diabetes. PMID:24352680

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

2014-10-01

292

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

PubMed

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

Cohen, Irun R

2014-11-01

293

The role of microRNAs in autoimmune diseases with skin involvement.  

PubMed

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively modulate gene expression by binding to the 3' untranslated region (UTR) of target messenger RNAs (mRNAs), which leads to the degradation or translational repression of their target mRNAs. Previous research on miRNAs has revealed a new paradigm of gene regulations and pathways involved in the pathogenesis of autoimmune disorders and malignant diseases. The roles of miRNAs in cellular processes, including cell differentiation, proliferation, apoptosis and immune functions, are not clearly understood. MiRNAs are easily detected in a variety of sources, including tissues, serum, and other body fluids, and this make them a good biological sample for pathogenic studies and disease biomarker development. This review encompasses the current understanding of the roles of miRNAs in autoimmunity and the cellular and molecular mechanisms of miRNAs in various autoimmune diseases (AIMDs). Specifically, we focus on the target genes of miRNAs and the biological processes associated with autoimmune diseases with skin involvement, including systemic lupus erythematosus, psoriasis, systemic sclerosis, Behcet's disease, and dermatomyositis. In addition, the diagnostic and therapeutic relevance of miRNAs that are involved in autoimmunity are elucidated to provide information for clinical implications. This article is protected by copyright. All rights reserved. PMID:25430682

Deng, Xinjie; Su, Yuwen; Wu, Haijing; Wu, Ruifang; Zhang, Peng; Dai, Yong; Chan, Tak-Mao; Zhao, Ming; Lu, Qianjin

2014-11-27

294

Frequency distribution of autoimmunity associated FCGR3B gene copy number in Indian population.  

PubMed

Amongst several human genome variations, copy number variations (CNVs) are considered as an important source of variability contributing to susceptibility to wide range of diseases. Although CNV is scattered for genes throughout the human genome, several of autoimmunity related genes have CN variation and therefore play an important role in susceptibility to autoimmune diseases. The association of the Fc gamma receptor 3B (FCGR3B) gene copy number in autoimmunity is well characterized in various populations studied. The Fc gamma receptor is a low affinity, glycosylphosphatidylinositol-linked receptor for IgG molecule predominantly expressed on human neutrophils. The variable gene copy number of FCGR3B is found to be involved in the impaired clearance of immune complexes, which significantly contribute to the pathogenesis of several autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type-1 diabetes and others. The FCGR3B copy number ranged from 0 to ?2 copies per diploid genome in other populations, but yet not explored in Indian population. Hence, this study aims to evaluate the variation in the frequency distribution of FCGR3B CNV in Indian population. FCGR3B gene copy number varied significantly when compared to other population of the world. This observation will help us in exploring the potential role of CNV in FCGR3B gene and its association to autoimmune disorders in Indian population. PMID:25428402

Almal, S H; Padh, Harish

2015-02-01

295

Diagnosis and classification of autoimmune orchitis.  

PubMed

Autoimmune orchitis is characterized by testis inflammation and the presence of specific antisperm antibodies (ASA). It is classified in two categories. Primary autoimmune orchitis is defined by infertility and asymptomatic orchitis associated with ASA (100%) directed to the basement membrane or seminiferous tubules in infertile men, without any systemic disease and usually asymptomatic. Secondary autoimmune orchitis is characterized by symptomatic orchitis and/or testicular vasculiti`s associated with a systemic autoimmune disease, particularly vasculitis. These patients typically demonstrate testicular pain, erythema and/or swelling. ASA in secondary autoimmune orchitis have been reported in up to 50% of patients, especially in systemic lupus erythematosus patients. The pathogenesis of primary as well as secondary autoimmune orchitis is still unknown. Although the etiology is likely to be multifactorial, testicular inflammation, infection or trauma may induce T cell response with pro-inflammatory cytokine production with a consequent blood-testis-barrier permeability alteration, ASA production and apoptosis of spermatocytes and spermatids. ASA is known to cause immobilization and/or agglutination of spermatozoa, which may block sperm-egg interaction resulting in infertility. Assisted reproduction has been used as an efficient option in primary cases and immunosuppressive therapy for secondary autoimmune orchitis, although there is no double-blind, randomized trial to confirm the efficacy of any treatment regimens for these conditions. PMID:24424181

Silva, C A; Cocuzza, M; Carvalho, J F; Bonfá, E

2014-01-01

296

Liver transplantation and autoimmune hepatitis  

PubMed Central

Summary Liver Transplantation (LT) is an effective treatment for patients with end-stage liver disease including autoimmune hepatitis (AIH). Indication for LT for AIH does not differ basically from other liver diseases including both acute and chronic types of disease progression, although it is reported to be an infrequent indication for LT worldwide due to the therapeutic advances of immunosuppression. The outcome following LT is feasible, with current patient and graft survival exceeding 75% at 5 years. Recurrent and de-novo AIH posttranslant has also been reported; and this seems to have important clinical implications because its management differs from the standard treatment for allograft rejection. In this review, we discuss the characteristics of AIH, focusing on the indication for LT and issues raised following LT.

Tanaka, Tomohiro; Sugawara, Yasuhiko; Kokudo, Norihiro

2015-01-01

297

Autoimmune pancreatitis mimicking pancreatic tumor  

PubMed Central

Autoimmune pancreatitis (AIP) is a rare disease of unknown pathomechanism. It belongs to the IgG4-related disease family and responds well to steroids, although the relapse rate can reach up to 20–30%. Differentiating AIP from the more common pancreatic cancer can be very challenging. About 20% of AIP is diagnosed postoperatively during final histological examination. Each of the investigative tools can add something to the definitive diagnosis; the question remains whether it is possible to prevent an unnecessary resection. Through our case we would like to demonstrate the differential diagnostic opportunities and present the literary background of this issue. In conclusion, we can state that whenever a focal pancreatic lesion is encountered AIP should always be considered. PMID:24968399

Dede, Kristóf; Salamon, Ferenc; Taller, András; Tekn?s, Dániel; Bursics, Attila

2012-01-01

298

Autoimmune pancreatitis: A surgical dilemma.  

PubMed

Autoimmune pancreatitis (AIP) is defined as a particular form of pancreatitis that often manifests as obstructive jaundice associated with a pancreatic mass or an obstructive bile duct lesion, and that has an excellent response to corticosteroid treatment. The prevalence of AIP worldwide is unknown, and it is considered as a rare entity. The clinical and radiological presentation of AIP can mimic bilio-pancreatic cancer, presenting difficulties for diagnosis and obliging the surgeon to balance decision-making between the potential risk presented by the misdiagnosis of a deadly disease against the desire to avoid unnecessary major surgery for a disease that responds effectively to corticosteroid treatment. In this review we detail the current and critical points for the diagnosis, classification and treatment for AIP, with a special emphasis on surgical series and the methods to differentiate between this pathology and bilio-pancreatic cancer. PMID:25066570

Saavedra-Perez, David; Vaquero, Eva C; Ayuso, Juan R; Fernandez-Cruz, Laureano

2014-12-01

299

Autosomal recessive chronic granulomatous disease, IgA deficiency and refractory autoimmune thrombocytopenia responding to Anti-CD20 monoclonal antibody.  

PubMed

Immunodeficiency and autoimmune disease may occur concomitantly in the same individual. Some of the immunodeficiency syndromes, especially humoral defects are associated with autoimmune disorders. Hematological manifestations such as thrombocytopenia and hemolytic anemia are the most common presentations. Persistent antigen stimulation due to an inherent defect in the ability of the immune system to eradicate pathogens is the primary cause leading to autoimmunity in patients with primary immunodeficiency states.We describe a 10 year old Iranian girl with chronic granulomatous disease -the autosomal recessive type with mutation of NCF1 gene P47- associated with selective IgA deficiency, refractory immune thrombocytopenia that showed an excellent response to Rituximab (Anti-CD20 monoclonal antibody).Patients with primary immunodeficiencies may have variable autoimmune manifestations. So for early detection and appropriate treatment, autoimmune diseases should always be suspected in such patients. PMID:18780954

Shamsian, Bibi Shahin; Mansouri, Davoud; Pourpak, Zahra; Rezaei, Nima; Chavoshzadeh, Zahra; Jadali, Farzaneh; Gharib, Atoosa; Alavi, Samin; Eghbali, Aziz; Arzanian, Mohammad Taghi

2008-09-01

300

Natural killer cells in human autoimmune diseases  

PubMed Central

Natural killer (NK) cells have been implicated in tumour surveillance and in the early control of several microbial infections. In autoimmune disease their involvement in these processes has been evaluated in animal models, with conflicting results. Both a disease-controlling and a disease-promoting role have been suggested. In human autoimmune disease only a few studies, mainly descriptive, have demonstrated qualitative and quantitative modification of NK cells. These changes were observed on blood- or tissue-infiltrating NK cells. Taken together with our expanding knowledge of the genetical variability of NK cell receptors and NK cell physiology, these findings pave the way for the dissection of the role of NK cells in human autoimmune diseases. NK cells may be directly involved in these diseases through their potential autoreactivity or through their interaction with dendritic cells, macrophages or T lymphocytes, thereby inducing excessive inflammation or favouring the adaptive autoimmune response. Thus, NK cells may be implicated in the onset, the maintenance or the progression of autoimmune diseases. Some reports also suggest the involvement of NK cells in the treatment of human autoimmune disease by biotherapies. All these observations suggest that NK cells are involved in the complex processes of autoimmune diseases. Nevertheless, further careful analysis of NK cells at different steps of these diseases, in different tissues and through combined genetical and functional studies will contribute to a better understanding of their role in autoimmune diseases. This knowledge might allow the development of new therapeutic strategies based on NK cells for the treatment of some autoimmune diseases. PMID:21039469

Schleinitz, Nicolas; Vély, Frédéric; Harlé, Jean-Robert; Vivier, Eric

2010-01-01

301

Phosphodiesterase 4-targeted treatments for autoimmune diseases  

PubMed Central

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

2013-01-01

302

Celiac Disease and Autoimmune-Associated Conditions  

PubMed Central

Celiac disease (CD) is frequently accompanied by a variety of extradigestive manifestations, thus making it a systemic disease rather than a disease limited to the gastrointestinal tract. This is primarily explained by the fact that CD belongs to the group of autoimmune diseases. The only one with a known etiology is related to a permanent intolerance to gluten. Remarkable breakthroughs have been achieved in the last decades, due to a greater interest in the diagnosis of atypical and asymptomatic patients, which are more frequent in adults. The known presence of several associated diseases provides guidance in the search of oligosymptomatic cases as well as studies performed in relatives of patients with CD. The causes for the onset and manifestation of associated diseases are diverse; some share a similar genetic base, like type 1 diabetes mellitus (T1D); others share pathogenic mechanisms, and yet, others are of unknown nature. General practitioners and other specialists must remember that CD may debut with extraintestinal manifestations, and associated illnesses may appear both at the time of diagnosis and throughout the evolution of the disease. The implementation of a gluten-free diet (GFD) improves the overall clinical course and influences the evolution of the associated diseases. In some cases, such as iron deficiency anemia, the GFD contributes to its disappearance. In other disorders, like T1D, this allows a better control of the disease. In several other complications and/or associated diseases, an adequate adherence to a GFD may slow down their evolution, especially if implemented during an early stage. PMID:23984314

Lauret, Eugenia; Rodrigo, Luis

2013-01-01

303

Autoimmune and autoinflammatory mechanisms in uveitis.  

PubMed

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders. PMID:24858699

Lee, Richard W; Nicholson, Lindsay B; Sen, H Nida; Chan, Chi-Chao; Wei, Lai; Nussenblatt, Robert B; Dick, Andrew D

2014-09-01

304

Thyroid autoimmunity in children and adolescents with newly diagnosed type 1 diabetes mellitus  

PubMed Central

Purpose This study aim to investigate the occurrence of autoimmune thyroid disease in children and adolescents at onset of type 1 diabetes mellitus (T1DM) and to assess whether the presence of diabetes-specific autoantibodies can predict the autoimmune thyroid disorder. Methods Seventy-three children with T1DM were recruited. Glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), insulin autoantibodies (IAA), and thyroid antibodies were determined in all patients at the time of diagnosis. Results The majority of patients (87.7%) had at least one pancreatic antibody (74.0% for GADA, 20.5% for ICA, and 24.7% for IAA). Thyroid autoantibodies were found in 19 of 73 patients (26.0%) at diagnosis. Thyroid autoimmunity (TA) incidence was not statistically significant by GADA or ICA positivity, but significantly higher by IAA positivity (P=0.03), and IAA positivity showed odds ratio, 4.931; 95% confidence interval, 1.323-18.381 for TA. Conclusion The IAA positivity in children and adolescents with TIDM was strongly related to positivity of thyroid autoantibodies and thus it could serve as an index for early prediction of the development of the thyroid autoimmune disorder among children and adolescents with TIDM. PMID:25077089

Jung, Eui Seok; Han, Dong Kyun; Yang, Eun Mi; Kim, Min Sun; Lee, Dae-Yeol

2014-01-01

305

Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies  

Microsoft Academic Search

OBJECTIVESTo review the autoimmune and rheumatic manifestations of patients with malignancy.METHODSA Medline search of all published papers using keywords related to malignancies, autoimmunity, rheumatic diseases, and paraneoplastic syndromes.RESULTSPatients with malignant diseases may develop autoimmune phenomena and rheumatic diseases as a result of (a) generation of autoantibodies against various autoantigens, including oncoproteins (P185, 1-myc, c-myc, c-myb), tumour suppression genes (P53), proliferation

M Abu-Shakra; D Buskila; M Ehrenfeld; K Conrad; Y Shoenfeld

2001-01-01

306

Hepatitis C-associated rheumatic disorders.  

PubMed

Hepatitis C virus (HCV) is an important causative agent of liver diseases. However, HCV infection is also associated with numerous hematologic, renal, dermatologic, rheumatic, and autoimmune disorders. These include arthralgia, arthritis, vasculitis, sicca syndrome, myalgia, and fibromyalgia. The purpose of this article is to review the prevalence and spectrum of rheumatic disorders and autoimmune phenomena in HCV-infected patients. It evaluates and current treatment options including nonsteroidal anti-inflammatory drugs, low-dose corticosteroids, hydroxychloroquine, methotrexate, penicillamine, combined antiviral therapy, cyclosporin A, anti-TNF-a agents, and rituximab. It concludes that larger, controlled studies are needed to establish further the treatment indications, efficacy, and safety of these agents. PMID:19481000

Buskila, Dan

2009-02-01

307

Autoimmune disease preceding amyotrophic lateral sclerosis  

PubMed Central

Objective: To study whether the risk of amyotrophic lateral sclerosis (ALS) is increased in people with prior autoimmune disease. Methods: An all-England hospital record-linkage dataset spanning 1999–2011 was used. Cohorts were constructed of people with each of a range of autoimmune diseases; the incidence of ALS in each disease cohort was compared with the incidence of ALS in a cohort of individuals without prior admission for the autoimmune disease. Results: There were significantly more cases than expected of ALS associated with a prior diagnosis of asthma, celiac disease, younger-onset diabetes (younger than 30 years), multiple sclerosis, myasthenia gravis, myxedema, polymyositis, Sjögren syndrome, systemic lupus erythematosus, and ulcerative colitis. Conclusions: Autoimmune disease associations with ALS raise the possibility of shared genetic or environmental risk factors. PMID:23946298

Goldacre, Raph; Ramagopalan, Sreeram; Talbot, Kevin; Goldacre, Michael J.

2013-01-01

308

Shaking Out Clues to Autoimmune Disease  

MedlinePLUS

... Among their findings was a potential link with salt consumption. Autoimmune diseases arise when the immune system, ... may affect Th17 cell development. In a high-salt solution, naive T cells expressed the gene for ...

309

Autoimmune autonomic ganglionopathy after a CNS infection.  

PubMed

We report the first Greek case of autoimmune autonomic ganglionopathy seropositive for antibodies against ganglionic acetylcholine receptors, unique for an antecedent viral cerebellitis and long, slowly progressive course, with improvement after treatment with pyridostigmine. PMID:21210293

Maiovis, Pantelis; Ioannidis, Panagiotis; Balamoutsos, George; Karacostas, Dimitris

2011-06-01

310

Cell damage and autoimmunity: a critical appraisal.  

PubMed

In April 2007, an international Colloquium bridging scientific and clinical disciplines was held to discuss the role of cellular and tissue damage in the initiation, development and persistence of autoimmune disease. Five potential etiologic and pathophysiologic processes fundamental to autoimmune disease (i.e. inflammation, infection, apoptosis, environmental exposure and genetics) were the focus of the presentations and integrative discussions at the Colloquium. The information presented on these topics is condensed in this review. Inflammation has close clinico-pathologic associations with autoimmunity, but future analyses will require better definition and metrics of inflammation, particularly for the earliest cellular and molecular components dependent on recruitment of elements of innate immunity. Although infection may be associated with increased levels of autoantibodies, most infections and virtually all vaccinations in humans lack well-established links to autoimmune diseases. Further application of well-designed, long-term epidemiologic and population-based studies is urgently needed to relate antecedent exposures with later occurring stigmata of autoimmunity with a goal of discerning potentially susceptible individuals or subpopulations. Suspect infections requiring closer interrogation include EB virus (SLE and other diseases), HCV (autoimmune hepatitis), beta hemolytic streptococci (rheumatic carditis) and Helicobacter pylori (autoimmune gastritis) among others. And even if a micro-organism was to be incriminated, mechanisms of initiation/perpetuation of autoimmunity continue to challenge investigators. Plausible mechanisms include potentiation and diversion of innate immunity; exposure or spillage of intracellular autoantigens; or provision of autoantigenic mimics. Integrity of apoptosis as a critical safeguard against autoimmunity was discussed in the contexts of over-reactivity causing autoantigens to gain enhanced exposure to the immune system, or under-reactivity producing insufficient elimination of autoreactive clones of lymphocytes. Although environmental agents are widely believed to serve as necessary "triggers" of autoimmune disease in genetically predisposed individuals, only a few such agents (mainly drugs and some nutrients) have been clearly identified and their mechanism of action defined. Finally an essential genetic foundation underlies all these hazards for autoimmunity in the form of risk-associated polymorphisms in immunoregulatory genes. They may be predictive of future or impending disease. PMID:18194728

Mackay, Ian R; Leskovsek, Natasha V; Rose, Noel R

2008-01-01

311

Porous silicon biosensor for the detection of autoimmune diseases  

NASA Astrophysics Data System (ADS)

Advances in porous silicon (pSi) technology have led to the development of new sensitive biosensors. The unique optical properties of pSi renders the material a perfect candidate for optical transducers exploiting photoluminescence or white light interference effects. The ability of biosensors exploiting these transduction mechanisms to quickly and accurately detect biological target molecules affords an alternative to current bioassays such as enzyme-linked immunosorbent assays (ELISAs). Here, we present a pSi biosensor that was developed to detect antibodies against the autoimmune protein La. This protein is associated with autoimmune diseases including rheumatic disorders, systematic lupus erythematosus (SLE) and Sjogren's syndrome (SS). A fast and sensitive detection platform such as the one described here can be applied to the rapid diagnosis of these debilitating autoimmune diseases. The immobilisation of the La protein onto pSi films gave a protein receptor-decorated sensor matrix. A cascade of immunological reactions was then initiated to detect anti-La antibody on the functionalised pSi surface. In the presence of o-phenylenediamine (OPD), horseradish peroxidase (HRP)/H IIO II catalysed the formation of an oxidised radical species that accelerated pSi corrosion. pSi corrosion was detected as a blue-shift in the generated interference pattern, corresponding to a decrease in the effective optical thickness (EOT) of the pSi film. Compared to an ELISA, the pSi biosensor could detect the anti-La antibody at a similar concentration (500 - 125 ng/ml). Furthermore, we found that the experimental process can be significantly shortened resulting in detection of the anti-La antibody in 80 minutes compared to a minimum of 5 hours required for ELISA.

Jane, Andrew O.; Szili, Endre J.; Reed, Joanne H.; Gordon, Tom P.; Voelcker, Nicolas H.

2007-12-01

312

Is there a Common Genetic Basis for Autoimmune Diseases?  

PubMed Central

Autoimmune diseases (ADs) represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations. The commonality between them however, is the damage to tissues and organs that arises from the response to self-antigens. The presence of shared pathophysiological mechanisms within ADs has stimulated searches for common genetic roots to these diseases. Two approaches have been undertaken to sustain the “common genetic origin” theory of ADs. Firstly, a clinical genetic analysis showed that autoimmunity aggregates within families of probands diagnosed with primary Sjögren's (pSS) syndrome or type 1 diabetes mellitus (T1D). A literature review supported the establishment of a familiar cluster of ADs depending upon the proband's disease phenotype. Secondly, in a same and well-defined population, a large genetic association study indicated that a number of polymorphic genes (i.e. HLA-DRB1, TNF and PTPN22) influence the susceptibility for acquiring different ADs. Likewise, association and linkage studies in different populations have revealed that several susceptibility loci overlap in ADs, and clinical studies have shown that frequent clustering of several ADs occurs. Thus, the genetic factors for ADs consist of two types: those which are common to many ADs (acting in epistatic pleitropy) and those that are specific to a given disorder. Their identification and functional characterization will allow us to predict their effect as well as to indicate potential new therapeutic interventions. Both autoimmunity family history and the co-occurrence of ADs in affected probands should be considered when performing genetic association and linkage studies. PMID:17162361

Anaya, Juan-Manuel; Gómez, LuisMiguel; Castiblanco, John

2006-01-01

313

Targeting interleukin-6 in inflammatory autoimmune diseases and cancers.  

PubMed

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

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

2014-02-01

314

Association of systemic and thyroid autoimmune diseases  

Microsoft Academic Search

Objective: There are few large cohort studies available on the association of systemic and thyroid autoimmune diseases. In this study,\\u000a we wished to determine the association of Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) with systemic autoimmune diseases.\\u000a Methods: One thousand five hundred and seventeen patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic\\u000a sclerosis (SSc), mixed connective tissue

Zoltán Szekanecz; Katalin Dankó; Emese Kiss; Nóra Anna Szabó; Gabriella Sz?cs; Margit Zeher; Gyula Szegedi; Gyula Bakó; László Czirják

2006-01-01

315

Cutting-Edge Issues in Autoimmune Orchitis  

Microsoft Academic Search

Autoimmune orchitis is a relevant cause of decreased fecundity in males, and it is defined as a direct aggression to the testis\\u000a with the concomitant presence of anti-sperm antibodies (ASA). The presence of these specific antibodies has been observed\\u000a in approximately 5–12% of infertile male partners. Primary autoimmune orchitis is defined by isolated infertility with ASA\\u000a but without evidence of

Clovis A. Silva; Marcello Cocuzza; Eduardo F. Borba; Eloísa Bonfá

316

Coherent Somatic Mutation in Autoimmune Disease  

PubMed Central

Background Many aspects of autoimmune disease are not well understood, including the specificities of autoimmune targets, and patterns of co-morbidity and cross-heritability across diseases. Prior work has provided evidence that somatic mutation caused by gene conversion and deletion at segmentally duplicated loci is relevant to several diseases. Simple tandem repeat (STR) sequence is highly mutable, both somatically and in the germ-line, and somatic STR mutations are observed under inflammation. Results Protein-coding genes spanning STRs having markers of mutability, including germ-line variability, high total length, repeat count and/or repeat similarity, are evaluated in the context of autoimmunity. For the initiation of autoimmune disease, antigens whose autoantibodies are the first observed in a disease, termed primary autoantigens, are informative. Three primary autoantigens, thyroid peroxidase (TPO), phogrin (PTPRN2) and filaggrin (FLG), include STRs that are among the eleven longest STRs spanned by protein-coding genes. This association of primary autoantigens with long STR sequence is highly significant (). Long STRs occur within twenty genes that are associated with sixteen common autoimmune diseases and atherosclerosis. The repeat within the TTC34 gene is an outlier in terms of length and a link with systemic lupus erythematosus is proposed. Conclusions The results support the hypothesis that many autoimmune diseases are triggered by immune responses to proteins whose DNA sequence mutates somatically in a coherent, consistent fashion. Other autoimmune diseases may be caused by coherent somatic mutations in immune cells. The coherent somatic mutation hypothesis has the potential to be a comprehensive explanation for the initiation of many autoimmune diseases. PMID:24988487

Ross, Kenneth Andrew

2014-01-01

317

Translating Data from Animal Models into Methods for Preventing Human Autoimmune Diabetes Mellitus: Caveat Emptor and Primum non Nocere  

Microsoft Academic Search

Type 1 diabetes in humans is a serious autoimmune disorder of children that is still poorly understood, unpreventable, and irreversible. Study of its animal models, notably the NOD mouse and BB rat, has generated a wealth of information concerning genetics and immunopathogenesis, but that information has still not altered the way in which we treat children with diabetes. In this

Dale L. Greiner; Aldo A. Rossini; John P. Mordes

2001-01-01

318

47,XXX in an Adolescent with Premature Ovarian Failure and Autoimmune Disease  

Microsoft Academic Search

Background: Premature ovarian failure (POF) may be idiopathic or may be associated with genetic or autoimmune disorders. The 47,XXX karyotype has been associated with POF and other genitourinary anomalies.Case: A 17-year-old woman with a history of immune thrombocytopenic purpura was referred to the adolescent medicine clinic for evaluation of oligomenorrhea with secondary amenorrhea. Evaluation revealed hypergonadotrophic premature ovarian failure, a

C. M Holland

2001-01-01

319

Macrophage activation syndrome in a newborn infant born to a mother with autoimmune disease.  

PubMed

Macrophage activation syndrome (MAS) is a complication of rheumatic disorders characterized by cytopenia, multiple organ dysfunction and coagulopathy associated with an inappropriate activation of macrophage. In neonatal lupus erythematosus, MAS is rare but fatal, requiring early diagnosis and treatment for optimal outcome. We report a case of MAS in a neonate born to a mother with autoimmune disease, improved by treatment with steroid, intravenous immunoglobulin and cyclosporine. PMID:25627282

Park, J H; Kim, S H; Kim, H J; Lee, S J; Jeong, D C; Kim, S Y

2015-02-01

320

Prevalence of celiac disease in Turkish children with autoimmune thyroiditis.  

PubMed

The close association between celiac disease (CD) and autoimmune disorders is well documented in adult and pediatric patients. The aim of this study is to determine the prevalence of CD in Turkish children with autoimmune thyroiditis (AT). Sera from 101 children with AT (11 boys and 90 girls, from 2 to 18 years of age; mean age 12.28 +/- 3.26 years) and 103 healthy children (46 boys and 57 girls, from 3.5 to 17 years of age; mean age 12.18 +/- 3.11 years) were screened for CD using the IgA anti-tissue transglutaminase (IgA anti-tTG) antibody and total serum IgA. Small intestinal biopsy was offered to all antibody-positive patients. IgA anti-tTG was positive in eight children (7.9%) with AT. None of the serum samples of healthy children were positive for IgA anti-tTG antibody. Selective IgA deficiency was not detected in patients or controls. Intestinal biopsy was accepted by seven patients. In five patients (4.9%), subtotal villous atrophy was found. These findings indicate that the prevalence of CD is higher in Turkish children with AT than in healthy controls. Routine screening for CD should be performed in children with AT. PMID:18716873

Sari, Sinan; Yesilkaya, Ediz; Egritas, Odul; Bideci, Aysun; Dalgic, Buket

2009-04-01

321

Combined short-term immunotherapy for experimental autoimmune myasthenia gravis  

SciTech Connect

A therapeutic strategy was designed to eliminate the humoral immune response to acetylcholine receptor (AChR) in ongoing experimental autoimmune myasthenia gravis (EAMG). Rats with EAMG were treated with a protocol consisting of three components: (1) A single high dose of cyclophosphamide (200 mg/kg) was used to produce a rapid and sustained fall in the anti-AChR antibody levels by preferential destruction of antibody-producing B-lymphocytes. ''Memory'' lymphocytes were not eliminated by cyclophosphamide. (2) Irradiation (600 rads) was used to eliminate the ''memory'' cells. It eliminated the anamnestic response to a challenge with the antigen AChR. (3) Bone marrow transplantation was used to repopulate the hematopoietic system after the otherwise lethal dose of cyclophosphamide. We used bone marrow from syngeneic rats with active EAMG to simulate an autologous transplant. Rats with EAMG treated with this combined protocol showed a prompt and sustained fall in the anti-AChR antibody levels and had no anamnestic response to a challenge with AChR. Thus, an affected animal's own marrow could be stored and used later for repopulation after cyclophosphamide-irradiation treatment. This treatment eliminates the animal's ongoing immune responses and reconstitutes the immune system in its original state. The success of this approach suggests that, if their safety could be established, similar ''curative'' strategies might be developed for the treatment of patients with severe antibody-mediated autoimmune disorders, such as myasthenia gravis.

Pestronk, A.; Drachman, D.B.; Teoh, R.; Adams, R.N.

1983-08-01

322

Autoimmune thyroid disease: mechanism, genetics and current knowledge.  

PubMed

Recent epidemiological studies recognized a steady increase in the incidence of different autoimmune endocrine disorders, including autoimmune thyroid disease (AITD). The etiology of AITD is multifactorial and involves genetic and environmental factors and apparently with a strong preponderance in females. There are mainly two types of AITD, Graves' disease and Hashimoto's disease and both of these show strong association in age groups above 45-50 years. Among environmental factors smoking and alcohol have significant effects, both protective as well as for aggravating the disease, even though the precise nature of these effects are not clearly known. There are elevated levels of circulating antibodies against the thyroid proteins, mainly thyroid oxidase, thyroglobulin and thyroid stimulating hormone receptor, in patients with Graves' disease or Hashimoto's disease. Linkage and association studies in AITD identified several major genes that are relevant for the onset of AITD, including the thyroid-specific genes, thyroglobulin and thyroid-stimulating hormone receptor and also many immune-regulatory genes. In this review we addressed many aspects of AITD including disease mechanisms, involved thyroid antigens, environmental factors and genetic factors. PMID:25535130

Dong, Y H; Fu, D G

2014-12-01

323

CD226 Gly307Ser association with multiple autoimmune diseases.  

PubMed

Genome-wide association studies provide insight into multigenic diseases through the identification of susceptibility genes and etiological pathways. In addition, the identification of shared variants among autoimmune disorders provides insight into common disease pathways. We previously reported an association of a nonsynonymous single nucleotide polymorphism (SNP) rs763361/Gly307Ser in the immune response gene CD226 on chromosome 18q22 with type 1 diabetes (T1D) susceptibility. Here, we report efforts toward identifying the causal variant by exonic resequencing and tag SNP mapping of the 18q22 region in both T1D and multiple sclerosis (MS). In addition to the analysis of newly available samples in T1D (2088 cases and 3289 controls) and autoimmune thyroid disease (AITD) (821 cases and 1920 controls), resulting in strong support for the Ser(307) association with T1D (P=3.46 x 10(-9)) and continued potential evidence for AITD (P=0.0345), we provide evidence for association of Gly307Ser with MS (P=4.20 x 10(-4)) and rheumatoid arthritis (RA) (P=0.017). The Ser(307) allele of rs763361 in exon 7 of CD226 predisposes to T1D, MS, and possibly AITD and RA, and based on the tag SNP analysis, could be the causal variant. PMID:18971939

Hafler, J P; Maier, L M; Cooper, J D; Plagnol, V; Hinks, A; Simmonds, M J; Stevens, H E; Walker, N M; Healy, B; Howson, J M M; Maisuria, M; Duley, S; Coleman, G; Gough, S C L; Worthington, J; Kuchroo, V K; Wicker, L S; Todd, J A

2009-01-01

324

Vitamin D Status and Concomitant Autoimmunity in Celiac Disease  

PubMed Central

Goals To determine whether patients with celiac disease and low vitamin D levels also have a higher prevalence of other autoimmune diseases (AD) as compared to patients with normal vitamin D levels. Background Patients with CD carry a higher risk of other autoimmune disorders. Because of its immunoregulatory properties, vitamin D deficiency has been proposed in the pathogenesis of a variety of AD. Whether low vitamin D levels in patients with CD can predict concomitant AD is unknown. Study A retrospective cross-sectional study of 530 adult patients with CD and a 25-hydroxyvitamin D level on record at CUMC. Results 133 patients (25%) had vitamin D deficiency. The prevalence of AD was similar among those with normal vitamin D (11%), insufficiency (9%), and deficiency (12%, p=0.66). On multivariate analysis, adjusting for age of CD diagnosis and gender, vitamin D deficiency was not associated with AD (OR 1.35 95% CI 0.62–2.95). The risk of psoriasis was higher in patients with vitamin D deficiency (7% vs. 3%, p=0.04). Vitamin D deficiency was more common in those who presented with anemia (39%) than in those who did not (23% p=0.002). Conclusion Vitamin D deficiency in CD is common but does not predict AD. Psoriasis is increased in vitamin D deficient CD patients. Assessment of vitamin D appears to be a high-yield practice, especially in those CD patients who present with anemia. PMID:23328299

Tavakkoli, Anna; DiGiacomo, Daniel; Green, Peter H.; Lebwohl, Benjamin

2012-01-01

325

Characteristics and Prevalence of Latent Autoimmune Diabetes in Adults (LADA)  

PubMed Central

Diabetes, one of the most commonly seen metabolic disorders, is affecting a major area of population in many developing as well as most of the developed countries and is becoming an alarming concern for the rising cost of the healthcare system. Latent Autoimmune Diabetes in Adults (LADA) is a form of diabetes which is less recognized and underdiagnosed type of diabetes which appears to have characteristics of both type 1 (autoimmune in nature) and type 2 diabetes (adult age at onset and initial response to oral hypoglycemic agents). An epidemiological study was carried out on 500 patients in the western region of India. Various parameters such as age at onset, duration of diabetes, gender, basal metabolic index (BMI), type of diabetes, family history, HbA1c levels, cholesterol levels, and current treatment regimen were evaluated and correlated with type 1 and type 2 diabetes. Moreover, diagnostic markers for LADA, namely, GAD autoantibodies and C-peptide levels, were determined for 80 patients selected from the epidemiological study. Some of the results obtained were found to be consistent with the literature whereas some results were found to be contradictory to the existing data. PMID:22577577

Brahmkshatriya, Priyanka P.; Mehta, Anita A.; Saboo, Banshi D.; Goyal, Ramesh K.

2012-01-01

326

Current approaches for the treatment of autoimmune hemolytic anemia.  

PubMed

Autoimmune hemolytic anemia (AIHA) is an infrequent group of diseases defined by autoantibody mediated red blood cell destruction. Correct diagnosis and classification of this condition are essential to provide appropriate treatment. AIHA is divided into warm and cold types according to the characteristics of the autoantibody involved and by the presence of an underlying or associated disorder into primary and secondary AIHA. Due to its low frequency, treatment for AIHA is largely based on small prospective trials, case series, and empirical observations. This review describes in detail the different treatment approaches for autoimmune hemolytic anemia. Warm antibody type AIHA should be treated with steroids, to which most patients respond, although relapse can occur and maintenance doses are frequently required. Splenectomy is an effective second line treatment and can provide long-term remission without medication. Rituximab is a useful alternative for steroid refractory patients, those requiring high maintenance doses and unfavorable candidates for surgery. Promising therapeutic modifications with this monoclonal antibody are emerging including drug combinations, lower doses, and long-term use. Primary cold agglutinin disease has been recognized as having a lymphoproliferative monoclonal origin. It is unresponsive to both steroids and splenectomy. Rituximab is currently the best therapeutic alternative for this condition, and several treatment regimens are available with variable responses. PMID:23689532

Jaime-Pérez, José Carlos; Rodríguez-Martínez, Marisol; Gómez-de-León, Andrés; Tarín-Arzaga, Luz; Gómez-Almaguer, David

2013-10-01

327

Expert Panel Workshop Consensus Statement on the Role of the Environment in the Development of Autoimmune Disease  

PubMed Central

Autoimmune diseases include 80 or more complex disorders characterized by self-reactive, pathologic immune responses in which genetic susceptibility is largely insufficient to determine disease onset. In September 2010, the National Institute of Environmental Health Sciences (NIEHS) organized an expert panel workshop to evaluate the role of environmental factors in autoimmune diseases, and the state of the science regarding relevant mechanisms, animal models, and human studies. The objective of the workshop was to analyze the existing data to identify conclusions that could be drawn regarding environmental exposures and autoimmunity and to identify critical knowledge gaps and areas of uncertainty for future study. This consensus document summarizes key findings from published workshop monographs on areas in which “confident” and “likely” assessments were made, with recommendations for further research. Transcribed notes and slides were reviewed to synthesize an overview on exposure assessment and questions addressed by interdisciplinary panels. Critical advances in the field of autoimmune disease research have been made in the past decade. Collaborative translational and interdisciplinary research is needed to elucidate the role of environmental factors in autoimmune diseases. A focus on exposure assessment methodology is needed to improve the effectiveness of human studies, and more experimental studies are needed to focus on causal mechanisms underlying observed associations of environmental factors with autoimmune disease in humans. PMID:25196523

Parks, Christine G.; Miller, Frederick W.; Pollard, Kenneth Michael; Selmi, Carlo; Germolec, Dori; Joyce, Kelly; Rose, Noel R.; Humble, Michael C.

2014-01-01

328

Myeloid cells, BAFF, and IFN-? establish an inflammatory loop that exacerbates autoimmunity in Lyn-deficient mice  

PubMed Central

Autoimmunity is traditionally attributed to altered lymphoid cell selection and/or tolerance, whereas the contribution of innate immune cells is less well understood. Autoimmunity is also associated with increased levels of B cell–activating factor of the TNF family (BAFF; also known as B lymphocyte stimulator), a cytokine that promotes survival of self-reactive B cell clones. We describe an important role for myeloid cells in autoimmune disease progression. Using Lyn-deficient mice, we show that overproduction of BAFF by hyperactive myeloid cells contributes to inflammation and autoimmunity in part by acting directly on T cells to induce the release of IFN-?. Genetic deletion of IFN-? or reduction of BAFF activity, achieved by either reducing myeloid cell hyperproduction or by treating with an anti-BAFF monoclonal antibody, reduced disease development in lyn?/? mice. The increased production of IFN-? in lyn?/? mice feeds back on the myeloid cells to further stimulate BAFF release. Expression of BAFF receptor on T cells was required for their full activation and IFN-? release. Overall, our data suggest that the reciprocal production of BAFF and IFN-? establishes an inflammatory loop between myeloid cells and T cells that exacerbates autoimmunity in this model. Our findings uncover an important pathological role of BAFF in autoimmune disorders. PMID:20624892

Scapini, Patrizia; Hu, Yongmei; Chu, Ching-Liang; Migone, Thi-Sau; DeFranco, Anthony L.; Cassatella, Marco A.

2010-01-01

329

Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment  

PubMed Central

Autoimmunity and immune dysregulation may lead to cytopenia and represent key features of many primary immunodeficiencies (PIDs). Especially when cytopenia is the initial symptom of a PID, the order and depth of diagnostic steps have to be performed in accordance with both an immunologic and a hematologic approach and will help exclude disorders such as systemic lupus erythematosus, common variable immunodeficiency, and autoimmune lymphoproliferative syndromes, hemophagocytic disorders, lymphoproliferative diseases, and novel differential diagnoses such as MonoMac syndrome (GATA2 deficiency), CD27 deficiency, lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency, activated PI3KD syndrome (APDS), X-linked immunodeficiency with magnesium defect (MAGT1 deficiency), and others. Immunosuppressive treatment often needs to be initiated urgently, which impedes further relevant immunologic laboratory analyses aimed at defining the underlying PID. Awareness of potentially involved disease spectra ranging from hematologic to rheumatologic and immunologic disorders is crucial for identifying a certain proportion of PID phenotypes and genotypes among descriptive diagnoses such as autoimmune hemolytic anemia, chronic immune thrombocytopenia, Evans syndrome, severe aplastic anemia/refractory cytopenia, and others. A synopsis of pathomechanisms, novel differential diagnoses, and advances in treatment options for cytopenias in PID is provided to facilitate multidisciplinary management and to bridge different approaches. PMID:25163701

2014-01-01

330

Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment.  

PubMed

Autoimmunity and immune dysregulation may lead to cytopenia and represent key features of many primary immunodeficiencies (PIDs). Especially when cytopenia is the initial symptom of a PID, the order and depth of diagnostic steps have to be performed in accordance with both an immunologic and a hematologic approach and will help exclude disorders such as systemic lupus erythematosus, common variable immunodeficiency, and autoimmune lymphoproliferative syndromes, hemophagocytic disorders, lymphoproliferative diseases, and novel differential diagnoses such as MonoMac syndrome (GATA2 deficiency), CD27 deficiency, lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency, activated PI3KD syndrome (APDS), X-linked immunodeficiency with magnesium defect (MAGT1 deficiency), and others. Immunosuppressive treatment often needs to be initiated urgently, which impedes further relevant immunologic laboratory analyses aimed at defining the underlying PID. Awareness of potentially involved disease spectra ranging from hematologic to rheumatologic and immunologic disorders is crucial for identifying a certain proportion of PID phenotypes and genotypes among descriptive diagnoses such as autoimmune hemolytic anemia, chronic immune thrombocytopenia, Evans syndrome, severe aplastic anemia/refractory cytopenia, and others. A synopsis of pathomechanisms, novel differential diagnoses, and advances in treatment options for cytopenias in PID is provided to facilitate multidisciplinary management and to bridge different approaches. PMID:25163701

Seidel, Markus G

2014-10-01

331

Molecular mimicry as a mechanism for food immune reactivities and autoimmunity.  

PubMed

The mucosal immune system is constantly exposed to challenges from the antigenic substances found in food and released from the body's own microbial flora. The body's normal tolerance to friendly antigenic substances can be disrupted by a number of factors, such as disease, injury, shock, trauma, surgery, drugs, blood transfusion, environmental triggers, etc. When this disruption happens, the ingestion of foods containing antigenic substances that have compositions similar to those of the body's autoantigens can result in the production of antibodies that react not only against the food antigens but also the body's own tissues. This response is known as food autoimmune reactivity. Between 7% and 10% of the world's population suffers from some form of autoimmune disease. Each patient's antibodies, both immunoglobulin A (IgA) + immunoglobulin M (IgM) in the saliva and immunoglobulin G (IgG) and IgA in the blood must be examined to give a complete picture of food immune reactivity. A host of health problems and autoimmune disorders have increasingly become associated with some of the most commonly consumed foods in the world, such as wheat and milk. Many of these problems can be traced to molecular mimicry. The peptide sequences of foods such as milk and wheat are similar to those of human molecules, such as myelin oligodendrocyte glycoprotein, human islet cell tissue, and human aquaporin 4 (AQP4). This similarity can result in cross-reactivity that leads to food autoimmunity and even autoimmune disorders, such as multiple sclerosis (MS), celiac disease (CD), and neuromyelitis optica. Further research is needed to determine what other foods have dangerous sequence similarities to human tissues and what methods are available to test for the autoantibodies resulting from these molecular, mimicry-induced misfires of the immune system. The identification and removal of corresponding food triggers can then be used as the basis of therapy. PMID:25599184

Vojdani, Aristo

2015-01-01

332

Autoimmune markers in children with chronic pancreatitis  

PubMed Central

Introduction In the last decade we can observe a gradual increase in the incidence of autoimmune diseases. The aetiology of chronic pancreatitis (CP) in children is varied and includes gene mutations, anatomic anomalies and others. The reported paediatric experience with chronic CP is scarce and little is known about the role of autoimmune pancreatitis (AIP). Aim To assess the frequency of autoimmune markers in children with CP. Material and methods One hundred and twenty-nine children hospitalised between 2005 and 2012 at the Department of Gastroenterology, The Children's Memorial Health Institute, were examined for the presence of AIP; the level of IgG4 was determined, and tests for anti-tissue antibodies (ANA, ASMA, AMA, ANCA, AHA) were conducted. Clinical data were recorded and analysed. Results Anti-tissue antibodies were detected in 75/129 children (58%), and 24/68 patients (35.3%) showed an increased IgG4 level. Based on the International Association of Pancreatology criteria, a suspicion of AIP was raised in 6 patients (4.6%). We found gene mutations predisposing to CP in 32/75 (42.6%) patients with autoimmune markers. In 16/75 children (21.3%), anatomic anomalies were found. There was no difference in the severity of the disease and clinical course between children with evidence of autoimmune process and patients without autoimmune markers (p = NS). Conclusions In children with CP, similarly to adults, there is a high frequency of biochemical markers of autoimmunity. It is worth remembering that AIP can occur in children. PMID:25097710

Cukrowska, Bo?ena; Kierku?, Jaros?aw; Ry?ko, Józef

2014-01-01

333

Intravenous immunoglobulins in autoimmune and inflammatory diseases: a mechanistic perspective.  

PubMed

Initially used for the treatment of immunodeficiencies, intravenous immunoglobulins (IVIg) have increasingly been used as immunomodulatory agents in autoimmune and inflammatory disorders. The mode of action of IVIg is enigmatic, probably involving Fc-dependent and/or F(ab')2-dependent nonexclusive mechanisms of action. IVIg broadly interacts with the different components of the immune system: cytokines, complement, Fc receptors, and several cell surface immunocompetent molecules. IVIg has also an impact on effector functions of immune cells. These mechanisms of action of IVIg reflect the importance of natural antibodies in the maintenance of immune homeostasis. We discuss here the recent advances in the understanding of immunoregulatory effects of IVIg, and we pointed out the need for new strategies to overcome the predicted increasing worldwide shortage of IVIg. PMID:17911465

Sibéril, Sophie; Elluru, Sriramulu; Graff-Dubois, Stéphanie; Negi, Vir-Singh; Delignat, Sandrine; Mouthon, Luc; Lacroix-Desmazes, Sébastien; Kazatchkine, Michel D; Bayry, Jagadeesh; Bayary, Jagadeesh; Kaveri, Srini V

2007-09-01

334

Asymmetric graves ophthalmopathy as a sole manifestation of autoimmune hypothyroidism  

PubMed Central

Graves ophthalmopathy (GO) is commonly associated with hyperthyroidism, however its coexistence with hypothyroidism is seen uncommonly in 5% of cases. The ophthalmic signs in GO are usually bilaterally symmetrical, however in 10–15% of cases patients may present asymmetrically. The ophthalmic signs in GO are commonly seen with other systemic features of thyroid disease, however when a patient present with asymmetric ophthalmic signs in the absence of other thyroid manifestations, it is difficult to consider the possibility of thyroid disorder, which may result in delayed diagnosis and further progression of disease. Here, we report a case of 22-year-old man who presented with progressive painless bulging of right eye without other features of thyroid disease which on workup was diagnosed as a case of autoimmune hypothyroidism. PMID:23291813

Verma, Sudhir Kumar; Jain, Nirdesh; Saraf, Sameer; Singh, Shailesh Kumar

2013-01-01

335

A case of rheumatic valvular heart disease and autoimmune gastritis.  

PubMed

We present a case of a 50-year-old female patient with a history of depressive disorder and anaemia (attributed to menorrhagias). She was admitted to the cardiology department with symptoms of fatigue on moderate exertion for several months, with worsening in the month before hospitalisation. Echocardiography revealed a severe mitral stenosis of rheumatic aetiology. Laboratory tests showed microcytic and hypochromic anaemia, reduced iron stores and vitamin B12 levels, and positive serum antiparietal cells autoantibodies. Endoscopy showed focal areas of erythema in the stomach, corresponding histologically to chronic atrophic gastritis. In this context, two distinct clinical entities were diagnosed in the same patient: severe rheumatic mitral stenosis and autoimmune gastritis. The patient was started on vitamin B12 and iron supplementation and underwent surgical correction of the valvular disease. There was symptomatic improvement in her signs of fatigue. PMID:25535234

Costa, Cátia; Durăo, David; Peres, Marisa; Leal, Margarida

2014-01-01

336

Saving Death: Apoptosis for Intervention in Transplantation and Autoimmunity  

PubMed Central

Long considered immunologically “bland,” apoptotic cells are now recognized as important modulators of immune responses. The role of apoptosis in immunological homeostasis has been inferred from several findings, for example, induction of tolerance after injection of apoptotic cells and the capacity of APCs like macrophages and DCs to induce and maintain tolerance after phagocytosis of dead cells. Processing of apoptotic cells by DCs is of particular interest, because DCs are the only known APCs capable of activating naďve T lymphocytes to become effector or regulatory cells. In that regard, recent evidence suggests that phagocytosis of apoptotic cells by DCs can induce Tregs, a finding that has significant implications for the treatment of a variety of immune-mediated inflammatory disorders. Here, we review the relationship between apoptotic cells, DCs, and Tregs, and its impact on prevention of transplant rejection and treatment of autoimmune diseases. PMID:17162368

Li, Alice; Ojogho, Okechukwu; Escher, Alan

2006-01-01

337

Bronchiolitis obliterans organizing pneumonia in patients with autoimmune rheumatic diseases.  

PubMed

Bronchiolitis obliterans organizing pneumonia (BOOP) is defined by buds of granulation tissue within lung distal airspaces. The diagnosis requires the histopathologic evidence of organizing pneumonia along with a suggestive clinical and radiographic pattern. This disorder is characterized by a good response to corticosteroids and an excellent prognosis. It can occur in association with a broad spectrum of clinical conditions or can be isolated, in this last case named cryptogenic organizing pneumonia. We searched for BOOP in patients with autoimmune rheumatic diseases (ARD) in the literature, and we found 32 well-documented cases. We reported here demographic features, manifestations, treatment and outcome of patients with BOOP associated with ARD. Notably, BOOP can be the presenting feature in some patients with ARD; thus, a close follow-up of patients with BOOP is recommended. PMID:25480740

Rojas, Carmen Maria Lara; Borella, Elisabetta; Palma, Lavinia; Ragozzino, Silvio; De Ramón, Enrique; Gomez-Huelgas, Ricardo; Punzi, Leonardo; Doria, Andrea

2014-12-01

338

Clues to immune tolerance: The monogenic autoimmune syndromes  

PubMed Central

Autoimmune disease affects a significant proportion of the population. The etiology of most autoimmune diseases is largely unknown, but it is thought to be multifactorial with both environmental and genetic influences. Rare monogenic autoimmune diseases, however, offer an invaluable window into potential disease mechanisms. In this review, we will discuss the autoimmune polyglandular syndrome (APS1), the immunedysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), and autoimmune lymphoproliferative syndrome (ALPS). Significantly, the information gained from the study of these diseases has provided new insights into more common autoimmune disease and have yielded new diagnostics and therapeutic opportunities. PMID:20969580

Waterfield, Michael; Anderson, Mark S.

2010-01-01

339

Everolimus improves experimental autoimmune uveoretinitis.  

PubMed

The efficacy and action mechanism of everolimus in the treatment of experimental autoimmune uveoretinitis (EAU) was analyzed. Disease was induced in B10.RIII mice by immunization with human interphotoreceptor-retinoid-binding protein peptide 161-180 (hIRBPp161-180). Everolimus was administered by oral gavage (5 mg/kg/d) beginning either two days before or 14 days after immunization. Everolimus significantly reduced the histopathological uveitis score compared to sham-treated mice. To examine the effect on the antigen-specific immune response, proliferation ([(3)H]-thymidine test) and delayed-type hypersensitivity (DTH) response were measured. Furthermore, content of T-helper-1, -2, and -17 cytokines were analyzed intraocularly (Bead Array) and in cell culture supernatants from splenocytes (sandwich ELISA). To study the effect on the humoral immune response the presence of antigen-specific serum antibodies was tested (indirect ELISA). The DTH, the humoral immune response, the proliferation of splenocytes and the intraocular Th1, Th2, Th17 cytokine content and in vitro production of Th1 and Th17 cytokines were impaired after everolimus treatment. The study of CD4+CD25+FoxP3+ regulatory T cells (T(reg)) in peripheral blood, draining lymph nodes, and spleen by flow cytometry showed an increased number of splenic T(reg) in mice of the everolimus therapy group. Furthermore the T(reg) of these mice had a higher suppressive capacity than cells from sham-treated mice. These results indicate that the immunosuppressive effect of everolimus on EAU was associated with the suppression of pathogenic effector responses and induction of regulatory T cells. PMID:23059401

Hennig, M; Bauer, D; Wasmuth, S; Busch, M; Walscheid, K; Thanos, S; Heiligenhaus, A

2012-12-01

340

Differentiating autoimmune pancreatitis from pancreatic cancer.  

PubMed

Differential diagnosis between autoimmune pancreatitis (AIP) and pancreatic cancer can be very difficult. The main clinical symptoms in patients with autoimmune pancreatitis are jaundice, weight loss, abdominal pain and new onset of diabetes mellitus. Unfortunately, the same symptoms could be observed in patients with pancreatic carcinoma too. Imaging methods as computed tomography (CT) scan, magnetic resonance imaging (MRI) and endosonography (EUS); together with serological examination (IgG4 and Ca 19-9) play the important role in differentiation autoimmune pancreatitis from pancreatic cancer. Extrapancreatic findings are distinctive in patients with autoimmune pancreatitis. In some cases the pancreatic biopsy is indicated, mainly in patients with focal or multifocal form of autoimmune pancreatitis. Response to steroids (decreased pancreatic or extrapancreatic lesion or damage) is distinctive to AIP. In clinical practice, CT scan seems to be the most reasonable tool for examining the patients with obstructive jaundice with or without present pancreatic mass. Stratification the patients with possible AIP versus pancreatic cancer is important. In patients with AIP it may avoid pancreatic resection, as well as incorrect steroid treatment in patients with pancreatic carcinoma. PMID:25288201

Díte, P; Uvírová, M; Bojková, M; Novotný, I; Dvorácková, J; Kianicka, B; Nechutová, H; Dovrtelová, L; Floreánová, K; Martínek, A

2014-12-01

341

Autoimmune diseases and infections: controversial issues.  

PubMed

The etiology and pathogenesis of certain types of disease remain controversial and stand like a bridge that crosses infectious, autoimmune and autoinflammatory pathways. Infection, for example, may initiate a disease, although it is the genetic regulation in the host, the interplay between virus or bacteria persistence and autoimmunity that produces the later phases of disease, the antigenic determinants responsible for inducing autoimmune disease, and the pathogenetic effector mechanisms. Infections agents cause pericarditis, but in 85% of cases it is "idiopathic". It has also been shown that persistent Clamydia pneumoniae, Porphyromonas gingivalis, and Helicobacter pylori infections cause host immunity and promote atherogenesis. A number of infectious agents have been suggested as potential triggers for primary biliary cirrhosis. Infections and vaccinations have also been linked to the pathogenesis of fibromyalgia syndrome, a common, chronic syndrome of widespread pain. Many factors are also responsible for fever of unknown origin such as: infections, autoimmunity disease, etc. However, it is difficult to determine a direct correlation between the infections agents in such a large group of diseases. The aim of this review is to analyze some of the controversies about the role of infections in autoimmune diseases. PMID:18570758

Baio, P; Brucato, A; Buskila, D; Gershwin, M E; Giacomazzi, D; Lopez, L R; Luzzati, R; Matsuura, E; Selmi, C; Sarzi-Puttini, P; Atzeni, F

2008-01-01

342

How I treat autoimmune lymphoproliferative syndrome  

PubMed Central

Autoimmune lymphoproliferative syndrome (ALPS) represents a failure of apoptotic mechanisms to maintain lymphocyte homeostasis, permitting accumulation of lymphoid mass and persistence of autoreactive cells that often manifest in childhood with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and recurring multilineage cytopenias. Cytopenias in these patients can be the result of splenic sequestration as well as autoimmune complications manifesting as autoimmune hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune neutropenia. More than 300 families with hereditary ALPS have now been described; nearly 500 patients from these families have been studied and followed worldwide over the last 20 years by our colleagues and ourselves. Some of these patients with FAS mutations affecting the intracellular portion of the FAS protein also have an increased risk of B-cell lymphoma. The best approaches to diagnosis, follow-up, and management of ALPS, its associated cytopenias, and other complications resulting from infiltrative lymphoproliferation and autoimmunity are presented. This trial was registered at www.clinicaltrial.gov as #NCT00001350. PMID:21885601

Oliveira, Joăo Bosco

2011-01-01

343

Anxiety Disorders  

MedlinePLUS

... Here we discuss six different anxiety disorders: generalized anxiety disorder social phobia panic disorder post-traumatic stress disorder obsessive-compulsive disorder specific phobias. Generalized Anxiety Disorder (GAD) Click for more information ...

344

Spleen Disorders  

MedlinePLUS

... Blood Cell Disorders Plasma Cell Disorders Leukemias Lymphomas Myeloproliferative Disorders Spleen Disorders Topics in Spleen Disorders Overview ... Streptococcus pneumoniae Back to Top Previous: Overview of Myeloproliferative Disorders Next: Enlarged Spleen Audio Figures Photographs Pronunciations ...

345

Range of Neurologic Disorders in Patients With Celiac Disease  

Microsoft Academic Search

Objective. During the past 2 decades, ce- liac disease (CD) has been recognized as a multisystem autoimmune disorder. A growing body of distinct neu- rologic conditions such as cerebellar ataxia, epilepsy, myoclonic ataxia, chronic neuropathies, and dementia have been reported, mainly in middle-aged adults. There still are insufficient data on the association of CD with various neurologic disorders in children,

Nathanel Zelnik; Avi Pacht; Raid Obeid; Aaron Lerner

2010-01-01

346

Association of autoimmune hepatitis and systemic lupus erythematodes: A case series and review of the literature  

PubMed Central

Liver test abnormalities have been described in up to 60% of patients with systemic lupus erythematodes (SLE) at some point during the course of their disease. Prior treatment with potentially hepatotoxic drugs or viral hepatitis is commonly considered to be the main cause of liver disease in SLE patients. However, in rare cases elevated liver enzymes may be due to concurrent autoimmune hepatitis (AIH). To distinguish whether the patient has primary liver disease with associated autoimmune clinical and laboratory features resembling SLE - such as AIH - or the elevation of liver enzymes is a manifestation of SLE remains a difficult challenge for the treating physician. Here, we present six female patients with complex autoimmune disorders and hepatitis. Patient charts were reviewed in order to investigate the complex relationship between SLE and AIH. All patients had coexisting autoimmune disease in their medical history. At the time of diagnosis of AIH, patients presented with arthralgia, abdominal complaints, cutaneous involvement and fatigue as common symptoms. All patients fulfilled the current diagnostic criteria of both, AIH and SLE. Remission of acute hepatitis was achieved in all cases after the initiation of immunosuppressive therapy. In addition to this case study a literature review was conducted. PMID:25253972

Beisel, Claudia; Weiler-Normann, Christina; Teufel, Andreas; Lohse, Ansgar W

2014-01-01

347

Role of Regulatory T Cells in a New Mouse Model of Experimental Autoimmune Myositis  

PubMed Central

Polymyositis is a rare and severe inflammatory muscle disorder. Treatments are partially efficacious but have many side effects. New therapeutic approaches must be first tested in a relevant animal model. Regulatory CD4+CD25+ T cells (Tregs) have been rediscovered as a pivotal cell population in the control of autoimmunity, but the connection between polymyositis and Tregs is currently unknown. To develop a reproducible experimental autoimmune myositis model of polymyositis, mice were immunized once a week for 3 weeks with 1 mg of partially purified myosin emulsified in complete Freund’s adjuvant. All mice injected with myosin and complete Freund’s adjuvant developed myositis. The infiltrates were composed of CD4+ and CD8+ cells, as well as macrophages, but did not contain B lymphocytes. In mice that were depleted of Tregs, the myositis was more severe, as determined by quantitative scoring of muscle inflammation (2.36 ± 0.9 vs. 1.64 ± 0.8, P = 0.019). In contrast, injection of in vitro expanded polyclonal Tregs at the time of immunization significantly improved the disease (quantitative score of inflammation 0.87 ± 1.06 vs. 2.4 ± 0.67, P = 0.047). Transfer of sensitized or CD4+-sorted cells from the lymph nodes of experimental autoimmune myositis mice induced myositis in naďve, irradiated, recipient mice. Thus, experimental autoimmune myositis is a reproducible, transferable disease in mice, both aggravated by Treg depletion and improved by polyclonal Treg injection. PMID:19218348

Allenbach, Yves; Solly, Sounkary; Grégoire, Sylvie; Dubourg, Odile; Salomon, Benoit; Butler-Browne, Gillian; Musset, Lucile; Herson, Serge; Klatzmann, David; Benveniste, Olivier

2009-01-01

348

Thymic epithelial defects and predisposition to autoimmune disease in BB rats.  

PubMed Central

We report an association between thymic epithelial defects and predisposition to autoimmunity. Diabetes-prone (DP) BB rats develop spontaneous hyperglycemia and are deficient in T cell subsets expressing the RT6 alloantigen. Diabetes resistant (DR) BB rats become diabetic if depleted of RT6+ T cells. The inciting immune system defects are unknown. We made the following observations: 1) Regions of thymic cortex and medulla devoid of thymic epithelium exist in DP-BB, DR-BB, and Lewis rats, all of which are susceptible to autoimmune disorders. Such defects were absent in eight normal rat strains. 2) Thymic epithelial defects are absent at birth, but present in BB rats at 4 weeks of age. 3) The genetic predisposition to thymic epithelial defects is an autosomal dominant trait. 4) The observation of thymic defects in (DP x WF)F1 rats led to the prediction that such animals, which never develop spontaneous autoimmunity, might be susceptible to its induction. Following depletion of RT6+ T cells we observed diabetes in 91%, and thyroiditis in 43%, of treated F1 animals (n = 23). Pancreatic insulitis was uniformly present. Because thymic epithelium participates in the positive and negative selection of developing thymocytes, we propose that thymic epithelial defects may play an important role in the predisposition of BB rats to autoimmunity. Images Figure 1 Figure 2 Figure 3 PMID:7992854

Doukas, J.; Mordes, J. P.; Swymer, C.; Niedzwiecki, D.; Mason, R.; Rozing, J.; Rossini, A. A.; Greiner, D. L.

1994-01-01

349

miRNAs at the crossroad between hematopoietic malignancies and autoimmune pathogenesis.  

PubMed

The study of microRNA (miRNA) regulation in the pathogenesis of autoimmune diseases and hematopoietic malignancies provides new understanding of the mechanisms of disease and is currently the focus of many researchers in the field. Autoimmune disorders and cancers of immune system comprise a wide range of genetically complex diseases that share certain aspects of dysregulated genetic networks, most notably deactivation of apoptosis. miRNA mechanisms control gene expression at the post-transcriptional level, linking mRNA processing and gene function. Considerable amount of data have been accumulated that indicate that the alteration of miRNA expression closely mirrors the development of immune system diseases and is likely to play a role in their pathogenesis. However, a knowledge gap remains in our understanding of how miRNA dysregulation and the specific effects of miRNAs on target gene expression underlay the disease phenotype. Here we review a number of studies describing miRNA alterations in autoimmune diseases and hematopoietic cancers and discuss potential miRNA-regulated mechanisms that differentially influence the development of autoimmunity as compared to cancer progression. PMID:22463797

Persengiev, Stephan P

2012-03-01

350

CD4+ CD25+ cells in type 1 diabetic patients with other autoimmune manifestations  

PubMed Central

The existence of multiple autoimmune disorders in diabetics may indicate underlying primary defects of immune regulation. The study aims at estimation of defects of CD4+ CD25+high cells among diabetic children with multiple autoimmune manifestations, and identification of disease characteristics in those children. Twenty-two cases with type 1 diabetes associated with other autoimmune diseases were recruited from the Diabetic Endocrine and Metabolic Pediatric Unit (DEMPU), Cairo University along with twenty-one normal subjects matched for age and sex as a control group. Their anthropometric measurements, diabetic profiles and glycemic control were recorded. Laboratory investigations included complete blood picture, glycosylated hemoglobin, antithyroid antibodies, celiac antibody panel and inflammatory bowel disease markers when indicated. Flow cytometric analysis of T-cell subpopulation was performed using anti-CD3, anti-CD4, anti-CD8, anti-CD25 monoclonal antibodies. Three cases revealed a proportion of CD4+ CD25+high below 0.1% and one case had zero counts. However, this observation did not mount to a significant statistical difference between the case and control groups neither in percentage nor absolute numbers. Significant statistical differences were observed between the case and the control groups regarding their height, weight centiles, as well as hemoglobin percentage, white cell counts and the absolute lymphocytic counts. We concluded that, derangements of CD4+ CD25+high cells may exist among diabetic children with multiple autoimmune manifestations indicating defects of immune controllers.

Elaziz, Dalia S. Abd; Hafez, Mona H.; Galal, Nermeen M.; Meshaal, Safa S.; El Marsafy, Aisha M.

2013-01-01

351

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

PubMed

Our understanding of the pathogenic mechanisms and possible treatments of autoimmune diseases has significantly increased over the past decade. Nonetheless, numerous major issues remain open and such issues span from epidemiology to clinimetrics and from the role of infectious agents to the search for accurate biomarkers in paradigmatic conditions such as systemic lupus erythematosus, rheumatoid arthritis, and spondyloarthropathies. In the case of cardiovascular comorbidities of autoimmune diseases or, more generally, the pathogenesis of atherosclerosis, fascinating evidence points to a central role of autoimmunity and metabolic dysfunctions and a possible role of therapies targeting inflammation to ameliorate both conditions. Basic science and translational medicine contribute to identify common mechanisms that underlie different autoimmune diseases, as in the case of tumor necrosis factor alpha, and more recently vitamin D, autoantibodies, T and B regulatory cells, and microRNA. Finally, new therapies are expected to significantly change our approach to autoimmune diseases, as represented by the recent FDA approval of the first oral JAK inhibitor. The present article moves from the major topics that were discussed at the 2013 Asian Congress of Autoimmunity in Hong Kong to illustrate the most recent data from leading journals in autoimmunity and immunology. PMID:24833503

Selmi, Carlo

2014-08-01

352

Clinical heterogeneity in autoimmune acute liver failure  

PubMed Central

AIM: To describe the outcome and prognosis in a cohort of patients with acute liver failure due to autoimmune hepatitis without liver transplantation. METHODS: A retrospective trial was conducted in 11 patients with acute liver failure due to autoimmune hepatitis who attended the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran. Demographic, biochemical and severity indexes, and treatment and outcome were assessed. RESULTS: Among the 11 patients, with a median age of 31 years, 72% had inflammatory response syndrome, and six patients received corticosteroids. The mortality rate within four weeks was 56%, and the one-year survival was 27%. In the survivors, severity indexes were lower and 83% received corticosteroids. CONCLUSION: We observed a relatively high survival rate in patients with acute liver failure due to autoimmune hepatitis. This survival rate could be influenced by severity of the disease and/or use of corticosteroids. PMID:17465474

Chavez-Tapia, Norberto C; Martinez-Salgado, Julio; Granados, Julio; Uribe, Misael; Tellez-Avila, Felix I

2007-01-01

353

Commensal microbiota influence systemic autoimmune responses.  

PubMed

Antinuclear antibodies are a hallmark feature of generalized autoimmune diseases, including systemic lupus erythematosus and systemic sclerosis. However, the processes underlying the loss of tolerance against nuclear self-constituents remain largely unresolved. Using mice deficient in lymphotoxin and Hox11, we report that approximately 25% of mice lacking secondary lymphoid organs spontaneously develop specific antinuclear antibodies. Interestingly, we find this phenotype is not caused by a defect in central tolerance. Rather, cell-specific deletion and in vivo lymphotoxin blockade link these systemic autoimmune responses to the formation of gut-associated lymphoid tissue in the neonatal period of life. We further demonstrate antinuclear antibody production is influenced by the presence of commensal gut flora, in particular increased colonization with segmented filamentous bacteria, and IL-17 receptor signaling. Together, these data indicate that neonatal colonization of gut microbiota influences generalized autoimmunity in adult life. PMID:25599993

Van Praet, Jens T; Donovan, Erin; Vanassche, Inge; Drennan, Michael B; Windels, Fien; Dendooven, Amélie; Allais, Liesbeth; Cuvelier, Claude A; van de Loo, Fons; Norris, Paula S; Kruglov, Andrey A; Nedospasov, Sergei A; Rabot, Sylvie; Tito, Raul; Raes, Jeroen; Gaboriau-Routhiau, Valerie; Cerf-Bensussan, Nadine; Van de Wiele, Tom; Eberl, Gérard; Ware, Carl F; Elewaut, Dirk

2015-02-12

354

Management of autoimmune associated alopecia areata.  

PubMed

Alopecia areata or hair loss occurs in one in 1000 people. If medical reasons for the hair loss are ruled out, opinion and hypothesis point towards autoimmunity and stress as possible causes. Dealing with the gradual or sudden loss of head hair, eyebrows, eyelashes, nasal, ear and body hair poses unique challenges for those it affects. Autoimmune-associated alopecia areata has no age boundaries and affects children, men and women equally. The dramatic change in appearance can result in psychological trauma, loss in confidence, bullying, low self-esteem and relationship difficulties. PMID:20527485

McKillop, Jaqueline

355

[Glycosylation of autoantibodies in autoimmunes diseases].  

PubMed

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

Goulabchand, R; Batteux, F; Guilpain, P

2013-12-01

356

MicroRNAs in Autoimmune Diseases  

PubMed Central

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

Qu, Zigang; Li, Wenhui; Fu, Baoquan

2014-01-01

357

Eosinophilic Fasciitis Associated with Autoimmune Thyroiditis  

PubMed Central

Eosinophilic fasciitis (EF) is scleroderma-like disease without Raynaud's phenomenon or visceral involvement. It is characterized by painful swelling of the extremities, accompanied by rapid weight gain, fever and myalgia. The acute state of disease is associated with significant peripheral blood eosinophilia, an elevated erythrocyte sedimentation rate and hypergammaglobulinemia. EF is also frequently associated with hematological abnormalities, including malignant lymphoproliferative diseases, but rarely associated with autoimmune thyroiditis. In the present study we report a case of eosinophilic fasciitis associated with autoimmune thyroiditis. PMID:16134777

Hur, Jin-Wuk; Lee, Hye-Soon; Uhm, Wan-Sik; Jun, Jae-Bum; Bae, Sang-Cheol; Park, Chan-Kum

2005-01-01

358

Antibody testing as a diagnostic tool in autonomic disorders  

Microsoft Academic Search

Some forms of peripheral autonomic dysfunction (especially enteric neuropathy and subacute panautonomic failure) occur as\\u000a autoimmune phenomena either in isolation or in the context of cancer. Autoimmune autonomic ganglionopathy is an example of\\u000a a severe, but potentially treatable, antibody-mediated form of autonomic failure. Diagnostic evaluation of autonomic disorders\\u000a can be supplemented by testing for paraneoplastic antibodies and antibodies against membrane

Steven Vernino

2009-01-01

359

Anxiety Disorders  

Microsoft Academic Search

The psychiatric disorders that are designated as anxiety disorders include the specific diagnoses of panic disorder with and\\u000a without agoraphobia, agoraphobia without history of panic disorder, specific phobia, social phobia, obsessive-compulsive disorder\\u000a (OCD), posttraumatic stress disorder (PTSD), acute stress disorder, generalized anxiety disorder (GAD), anxiety disorder due\\u000a to a general medical condition, substance-induced anxiety disorder, and anxiety disorder not otherwise

Julie Loebach Wetherell; Ariel J. Lang; Murray B. Stein

360

Impairment of Regulatory T-Cell Function in Autoimmune Thyroid Disease  

PubMed Central

Background Autoimmune thyroid disease (AITD) pathogenesis may result from a loss of immune tolerance to thyroid antigens. Regulatory T cells (Tregs) control immune responses, prevent excessive inflammation, and may be dysfunctional in AITD. We investigated the role of Tregs in Hashimoto's thyroiditis (HT) and Graves' disease (GD), complicated by Down syndrome (DS). Our goal was to identify differences in CD4+CD25high Treg function or number in patients with GD and HT, compared to healthy controls (HC). Methods Treg number was assessed by flow cytometric analysis in samples from 20 AITD patients (seven GD, 13 HT), nine HC, and seven individuals with DS, a genetic disorder associated with multiple autoimmune disorders including AITD. Treg function was assessed by the inhibition of proliferation (radioactive thymidine incorporation into DNA) of blood-derived T effector (Teff) cells by Tregs in a coculture. Various methods of stimulation were contrasted. Cytokine levels were determined in conditioned media from the co-cultures. Results No differences were found in the frequency of Tregs as a percentage of CD4+ cells between AITD and HC. AITD Tregs were less capable of inhibiting the proliferation of Teff cells when compared to HC; however, the impairment was dependent on the type of stimulation used. DS patients without AITD exhibited normal Treg function. We observed few differences in cytokine production between HC and AITD patients. Conclusions Tregs from AITD patients are partly dysfunctional, possibly explaining their autoimmunity. Future work will elucidate the diagnostic potential and pathophysiology of Tregs in AITD. PMID:23379353

Glick, Abigail B.; Wodzinski, Alaina; Fu, Pingfu

2013-01-01

361

Patterns of autoimmunity and subsequent chronic lymphocytic leukemia in Nordic countries  

PubMed Central

A population-based case-control study was conducted to evaluate risk of developing chronic lymphocytic leukemia (CLL) associated with personal and/or family history of autoimmune and related diseases. Data were obtained for all (n = 7764) patients diagnosed with CLL in Sweden and Denmark over a 40-year period and with linkable relatives, 16 658 matched control subjects, and first-degree relatives of patients (n = 17 991) and control subjects (n = 39 388). Odds ratios (ORs) were calculated to quantify risk of CLL in relation to personal/family history of 32 autoimmune and related disorders. The risk of CLL was significantly increased among subjects with a personal history of pernicious anemia (OR = 1.94; 1.18-3.18), mainly in the 0- to 1-year latency period. A significantly decreased risk of CLL was found among individuals with a personal history of chronic rheumatic heart disease (OR = 0.55; 0.33-0.93), particularly persons with a long latency (10+ years) between the 2 conditions. We found no association between personal or familial occurrence of other autoimmune or related disorders and CLL. If our results are confirmed, mechanistic studies examining how pernicious anemia might promote increased occurrence of CLL and how chronic rheumatic heart disease protects against CLL, perhaps related to long-term antibiotics use, may provide insights to the as-yet-unknown etiology of CLL. (Blood. 2006;108:292-296) PMID:16527887

Landgren, Ola; Engels, Eric A.; Caporaso, Neil E.; Gridley, Gloria; Mellemkjaer, Lene; Hemminki, Kari; Linet, Martha S.; Goldin, Lynn R.

2006-01-01

362

The HLA-G low expressor genotype confers protection against Bipolar Disorder  

E-print Network

1 The HLA-G low expressor genotype confers protection against Bipolar Disorder Monojit Debnath 1 processes such as inflammation and autoimmunity in bipolar disorder (BD) has recently gained increasing2013 #12;3 Key words Bipolar disorders HLA-G Polymorphism Immune modulation Seasonality of birth inserm

Paris-Sud XI, Université de

363

Autoimmunity in Coxsackievirus B3 induced myocarditis: role of estrogen in suppressing autoimmunity  

PubMed Central

SUMMARY Picornaviruses are small, non-enveloped, single stranded, positive sense RNA viruses which cause multiple diseases including myocarditis/dilated cardiomyopathy, type 1 diabetes, encephalitis, myositis, orchitis and hepatitis. Although picornaviruses directly kill cells, tissue injury primarily results from autoimmunity to self antigens. Viruses induce autoimmunity by: aborting deletion of self-reactive T cells during T cell ontogeny; reversing anergy of peripheral autoimmune T cells; eliminating T regulatory cells; stimulating self-reactive T cells through antigenic mimicry or cryptic epitopes; and acting as an adjuvant for self molecules released during virus infection. Most autoimmune diseases (SLE, rheumatoid arthritis, Grave’s disease) predominate in females, but diseases associated with picornavirus infections predominate in males. T regulatory cells are activated in infected females because of the combined effects of estrogen and innate immunity. PMID:20963181

2010-01-01

364

Pulmonary Autoimmunity as a Feature of Autoimmune Polyendocrine Syndrome Type 1 and Identification of KCNRG as a Bronchial Autoantigen  

E-print Network

Pulmonary Autoimmunity as a Feature of Autoimmune Polyendocrine Syndrome Type 1 and Identification of Nutrition, Metabolic Diseases and Endocrinology, University of Méditerranée, "La Timone" Hospital, Marseille and University Paris 7 Denis Diderot, 75019, Paris, France. Short title: Pulmonary Autoimmunity in APS-1

Paris-Sud XI, Université de

365

Autoimmune Adrenal Insufficiency and Autoimmune Polyendocrine Syndromes: Autoantibodies, Autoantigens, and Their Applicability in Diagnosis and Disease Prediction  

Microsoft Academic Search

Recent progress in the understanding of autoimmune adrenal disease, including a detailed analysis of a group of patients with Addison's disease (AD), has been reviewed. Criteria for defining an autoimmune disease and the main features of autoimmune AD (history, prevalence, etiology, histopathol- ogy, clinical and laboratory findings, cell-mediated and humoral immunity, autoantigens and their autoepitopes, ge- netics, animal models, associated

CORRADO BETTERLE; CHIARA DAL PRA; FRANCO MANTERO; RENATO ZANCHETTA

2002-01-01

366

Anti-Interferon Autoantibodies in Autoimmune Polyendocrinopathy Syndrome Type 1  

PubMed Central

Background The autoimmune regulator (AIRE) gene influences thymic self-tolerance induction. In autoimmune polyendocrinopathy syndrome type 1 (APS1; OMIM 240300), recessive AIRE mutations lead to autoimmunity targetting endocrine and other epithelial tissues, although chronic candidiasis usually appears first. Autoimmunity and chronic candidiasis can associate with thymomas as well. Patients with these tumours frequently also have high titre immunoglobulin G autoantibodies neutralising type I interferon (IFN)–? and IFN-?, which are secreted signalling proteins of the cytokine superfamily involved in both innate and adaptive immunity. Methods and Findings We tested for serum autoantibodies to type I IFNs and other immunoregulatory cytokines using specific binding and neutralisation assays. Unexpectedly, in 60/60 Finnish and 16/16 Norwegian APS1 patients with both AIRE alleles mutated, we found high titre neutralising immunoglobulin G autoantibodies to most IFN-? subtypes and especially IFN-? (60% homologous to IFN-?)—mostly in the earliest samples. We found lower titres against IFN-? (30% homologous to IFN-?) in 23% of patients; two-thirds of these (from Finland only) also had low titres against the distantly related “type III IFN” (IFN-?1; alias interleukin-29). However, autoantibodies to the unrelated type II IFN, IFN-?, and other immunoregulatory cytokines, such as interleukin-10 and interleukin-12, were much rarer and did not neutralise. Neutralising titres against type I IFNs averaged even higher in patients with APS1 than in patients with thymomas. Anti–type I IFN autoantibodies preceded overt candidiasis (and several of the autoimmune disorders) in the informative patients, and persisted for decades thereafter. They were undetectable in unaffected heterozygous relatives of APS1 probands (except for low titres against IFN-?1), in APS2 patients, and in isolated cases of the endocrine diseases most typical of APS1, so they appear to be APS1-specific. Looking for potentially autoimmunising cell types, we found numerous IFN-?+ antigen-presenting cells—plus strong evidence of local IFN secretion—in the normal thymic medulla (where AIRE expression is strongest), and also in normal germinal centres, where it could perpetuate these autoantibody responses once initiated. IFN-?2 and IFN-?8 transcripts were also more abundant in antigen-presenting cells cultured from an APS1 patient's blood than from age-matched healthy controls. Conclusions These apparently spontaneous autoantibody responses to IFNs, particularly IFN-? and IFN-?, segregate like a recessive trait; their high “penetrance” is especially remarkable for such a variable condition. Their apparent restriction to APS1 patients implies practical value in the clinic, e.g., in diagnosing unusual or prodromal AIRE-mutant patients with only single components of APS1, and possibly in prognosis if they prove to predict its onset. These autoantibody responses also raise numerous questions, e.g., about the rarity of other infections in APS1. Moreover, there must also be clues to autoimmunising mechanisms/cell types in the hierarchy of preferences for IFN-?, IFN-?8, IFN-?2, and IFN-? and IFN-?1. PMID:16784312

Meager, Anthony; Visvalingam, Kumuthini; Peterson, Pärt; Möll, Kaidi; Murumägi, Astrid; Krohn, Kai; Eskelin, Petra; Perheentupa, Jaakko; Husebye, Eystein; Kadota, Yoshihisa; Willcox, Nick

2006-01-01

367

Therapeutic antibodies for autoimmunity and inflammation  

Microsoft Academic Search

The development of therapeutic antibodies has evolved over the past decade into a mainstay of therapeutic options for patients with autoimmune and inflammatory diseases. Substantial advances in understanding the biology of human diseases have been made and tremendous benefit to patients has been gained with the first generation of therapeutic antibodies. The lessons learnt from these antibodies have provided the

Andrew C. Chan; Paul J. Carter

2010-01-01

368

Autoimmune myopathies: autoantibodies, phenotypes and pathogenesis.  

PubMed

The different autoimmune myopathies-for example, dermatomyositis, polymyositis, and immune-mediated necrotizing myopathies (IMNM)-have unique muscle biopsy findings, but they also share specific clinical features, such as proximal muscle weakness and elevated serum levels of muscle enzymes. Furthermore, around 60% of patients with autoimmune myopathy have been shown to have a myositis-specific autoantibody, each of which is associated with a distinct clinical phenotype. The typical clinical presentations of the autoimmune myopathies are reviewed here, and the different myositis-specific autoantibodies, including the anti-synthetase antibodies, dermatomyositis-associated antibodies, and IMNM-associated antibodies, are discussed in detail. This Review also focuses on a newly recognized form of IMNM that is associated with statin use and the production of autoantibodies that recognize 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the pharmacological target of statins. The contribution of interferon signaling to the development of dermatomyositis and the potential link between malignancies and the initiation of autoimmune myopathies are also assessed. PMID:21654717

Mammen, Andrew L

2011-06-01

369

Anti-cytokine autoantibodies in autoimmune diseases  

PubMed Central

An overview of the current literature is showing that autoantibodies (AutoAbs) against cytokines are produced in several pathological conditions, including autoimmune diseases, but can also be detected in healthy individuals. In autoimmune diseases, these AutoAbs may also be prognostic markers, either negative (such as AutoAbs to IL-8 and IL-1? in rheumatoid arthritis) or positive (such as AutoAbs to IL-6 in systemic sclerosis and those to osteopontin in rheumatoid arthritis). They may have neutralizing activity and influence the course of the physiological and pathological immune responses. High levels of AutoAbs against cytokines may even lead to immunodeficiency, such as those to IL-17 in autoimmune polyendocrine syndrome type I or those to IFN-? in mycobacterial infections. Their role in human therapy may be exploited not only through passive immunization but also through vaccination, which may improve the costs for long lasting treatments of autoimmune diseases. Detection and quantification of these AutoAbs can be profoundly influenced by the technique used and standardization of these methods is needed to increase the value of their analysis. PMID:23885320

Cappellano, Giuseppe; Orilieri, Elisabetta; Woldetsadik, Abiy D; Boggio, Elena; Soluri, Maria F; Comi, Cristoforo; Sblattero, Daniele; Chiocchetti, Annalisa; Dianzani, Umberto

2012-01-01

370

Autoimmune autonomic ganglionopathy after a CNS infection  

Microsoft Academic Search

We report the first Greek case of autoimmune autonomic ganglionopathy seropositive for antibodies\\u000a against ganglionic acetylcholine receptors, unique for an antecedent viral cerebellitis and long, slowly\\u000a progressive course, with improvement after treatment with pyridostigmine.

Pantelis Maiovis; Panagiotis Ioannidis; George Balamoutsos; Dimitris Karacostas

2011-01-01

371

Epigenetic alterations in autoimmune rheumatic diseases  

Microsoft Academic Search

The potential roles of epigenetic alterations in the pathogenesis of autoimmune rheumatic diseases are raising great expectations among clinicians and researchers. Epigenetic mechanisms regulate gene expression and are sensitive to external stimuli, bridging the gap between environmental and genetic factors. Considerable evidence of epigenetic changes, particularly altered patterns of DNA methylation, exists in diseases such as systemic lupus erythematosus (SLE)

Esteban Ballestar

2011-01-01

372

Type I interferons in systemic autoimmunity.  

PubMed

Type I IFN (IFN-I) was firstly described in 1957 as a soluble factor responsible for viral resistance in vitro. Today, it is well known that the IFN-I family comprises a wide number of cytokines with different modulatory effects on angiogenesis, cell growth, fibrosis, and apoptosis. However, one of the most important functions of IFN-I is the capability to trigger a complex array of cellular responses that result in a host-protective antiviral response. For this reason, IFN-I can be considered a "director" of protective immune responses. The recent finding of the so-called interferon signature in patients suffering from different autoimmune diseases has underlined its possible role in the pathogenesis of these diseases. On the other hand, IFN-alpha/beta is reported to be efficacious in the treatment of some autoimmune and infectious diseases not responsive to conventional therapy. On these occasions, the treated patients often start or increase autoantibody production supporting the role of IFN as inducer of an autoimmune response. In this review, we will underline recent acquisitions about IFN-I biology, with a focus on the relevance of the induction of some autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, dermato/polymiositis, and Sjogren's syndrome. PMID:20298124

Sozzani, Silvano; Bosisio, Daniela; Scarsi, Mirko; Tincani, Angela

2010-04-01

373

New insights into childhood autoimmune hemolytic anemia: a French national observational study of 265 children  

PubMed Central

Background Autoimmune hemolytic anemia is a rare condition in children. Little is known about its initial presentation and the subsequent progression of the disease. Design and Methods Since 2004, a national observational study has been aiming to thoroughly describe cases and identify prognostic factors. Patients from all French hematologic pediatric units have been included if they had a hemoglobin concentration less than 11 g/dL, a positive direct antiglobulin test and hemolysis. Evans’ syndrome was defined by the association of autoimmune hemolytic anemia and immunological thrombocytopenic purpura. Data from patients’ medical records were registered from birth to last follow-up. Autoimmune hemolytic anemia was classified as primary or secondary. Remission criteria, qualifying the status of anemia at last follow-up, were used with the aim of identifying a subgroup with a favorable prognosis in continuous complete remission. Results The first 265 patients had a median age of 3.8 years at diagnosis. In 74% of cases the direct antiglobulin test was IgG/IgG+C3d. Consanguinity was reported in 8% of cases and first degree familial immunological diseases in 15% of cases. Evans’ syndrome was diagnosed in 37% of cases. Autoimmune hemolytic anemia was post-infectious in 10%, immunological in 53% and primary in 37% of cases. After a median follow-up of 3 years, 4% of children had died, 28% were still treatment-dependent and 39% were in continuous complete remission. In multivariate analysis, IgG and IgG+C3d direct antiglobulin tests were associated with a lower rate of survival with continuous complete remission (adjusted hazard ratio, 0.43; 95% confidence interval, 0.21–0.86). Conclusions This nationwide French cohort is the largest reported study of childhood autoimmune hemolytic anemia. The rarity of this condition is confirmed. Subgroups with genetic predisposition and underlying immune disorders were identified. PMID:21228033

Aladjidi, Nathalie; Leverger, Guy; Leblanc, Thierry; Picat, Marie Quitterie; Michel, Gérard; Bertrand, Yves; Bader-Meunier, Brigitte; Robert, Alain; Nelken, Brigitte; Gandemer, Virginie; Savel, Hélčne; Stephan, Jean Louis; Fouyssac, Fanny; Jeanpetit, Julien; Thomas, Caroline; Rohrlich, Pierre; Baruchel, André; Fischer, Alain; Chęne, Genevičve; Perel, Y.

2011-01-01

374

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

PubMed

Interleukin-28A (IL-28A), a member of type III interferons (IFN-?s), promotes antiviral, antitumor and immune responses. However, its ability to regulate autoimmune diseases is poorly understood. In this study, we examined the effect of IL-28A on retinal antigen-induced experimental autoimmune uveoretinitis (EAU), a mouse model of human T-cell-mediated autoimmune eye disease. We found that administration of IL-28A enhanced EAU scores and autoimmune response parameters including delayed-type hypersensitivity (DTH), Ag-specific T cell proliferation and the production of Ag-specific IL-17 and IFN-? in the priming phase. The effect of IL-28A was abrogated by administration of a neutralizing antibody against IL-28A. Our results suggest that IL-28A is capable of exacerbating a T-cell-mediated autoimmune disease. Thus, targeting IL-28A may provide a new therapeutic approach to T cell-mediated autoimmune diseases such as uveitis. PMID:25138017

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

2014-12-01

375

A case of Kikuchi-Fujimoto disease with autoimmune thyroiditis  

PubMed Central

Kikuchi-Fujimoto disease (KFD) is a benign self-limiting disease characterized by fever and lymphadenitis. The etiology and pathogenesis of KFD is unclear. However, two hypotheses have been suggested: a viral infection hypothesis and an autoimmune hypothesis. Several KFD patients with various types of autoimmune diseases have been reported, and these reports support the hypothesis for autoimmune pathogenesis of KFD. Here, we report the case of a 17-year-old female patient diagnosed with KFD and autoimmune thyroiditis. This case serves as additional evidence that the etiology of KFD is autoimmune origin. PMID:23227065

Go, Eun Ji; Jung, You Jin; Han, Seung Beom; Suh, Byung Kyu

2012-01-01

376

The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.  

PubMed

Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-?- and polyinosine-polycytidylic acid [poly (I?:?C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD. PMID:24666275

Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E

2014-06-01

377

Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy  

PubMed Central

Nicotinic acetylcholine receptors (AChR) are ligand-gated cation channels that are present throughout the nervous system. The ganglionic (?3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic and enteric autonomic ganglia. Autonomic ganglia are an important site of neural integration and regulation of autonomic reflexes. Impaired cholinergic ganglionic synaptic transmission is one important cause of autonomic failure. Ganglionic AChR antibodies are found in many patients with autoimmune autonomic ganglionopathy (AAG). These antibodies recognize the ?3 subunit of the ganglionic AChR, and thus do not bind non-specifically to other nicotinic AChR. Patients with high levels of ganglionic AChR antibodies typically present with rapid onset of severe autonomic failure, with orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, bladder dysfunction and sicca symptoms. Impaired pupillary light reflex is often seen. Like myasthenia gravis, AAG is an antibody-mediated neurological disorder. Antibodies from patients with AAG inhibit ganglionic AChR currents and impair transmission in autonomic ganglia. An animal model of AAG in the rabbit recapitulates the important clinical features of the human disease and provides additional evidence that AAG is an antibody-mediated disorder caused by impairment of synaptic transmission in autonomic ganglia. PMID:18951069

Vernino, Steven; Hopkins, Steve; Wang, Zhengbei

2009-01-01

378

Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy.  

PubMed

Nicotinic acetylcholine receptors (AChR) are ligand-gated cation channels that are present throughout the nervous system. The ganglionic (alpha3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic and enteric autonomic ganglia. Autonomic ganglia are an important site of neural integration and regulation of autonomic reflexes. Impaired cholinergic ganglionic synaptic transmission is one important cause of autonomic failure. Ganglionic AChR antibodies are found in many patients with autoimmune autonomic ganglionopathy (AAG). These antibodies recognize the alpha3 subunit of the ganglionic AChR, and thus do not bind non-specifically to other nicotinic AChR. Patients with high levels of ganglionic AChR antibodies typically present with rapid onset of severe autonomic failure, with orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, bladder dysfunction and sicca symptoms. Impaired pupillary light reflex is often seen. Like myasthenia gravis, AAG is an antibody-mediated neurological disorder. Antibodies from patients with AAG inhibit ganglionic AChR currents and impair transmission in autonomic ganglia. An animal model of AAG in the rabbit recapitulates the important clinical features of the human disease and provides additional evidence that AAG is an antibody-mediated disorder caused by impairment of synaptic transmission in autonomic ganglia. PMID:18951069

Vernino, Steven; Hopkins, Steve; Wang, Zhengbei

2009-03-12

379

Ion channels in T lymphocytes: an update on facts, mechanisms and therapeutic targeting in autoimmune diseases.  

PubMed

During the last quarter of a century a large body of evidence was gathered about the involvement of ion channels in T lymphocyte activation. A series of remarkable findings promoted T cell ion channels to become potential pharmaceutical targets in the therapy of autoimmune disorders. Numerous comprehensive reviews describe the types of ion channels found in the plasma membrane of T cells and their roles in signaling pathways leading to activation, the changes in the expression of these channels brought upon by differentiation to various T cell subsets, the formation and possible functions of signaling molecular clusters that include ion channels in the immunological synapse, the discovery and refinement of structurally different ion channel blockers and the successful in vivo application of such compounds to suppress hypersensitivity reactions and autoimmune processes. In this review we wish to provide a concise update on these topics from recent years, highlighting the most notable developments. PMID:20026117

Varga, Zoltan; Hajdu, Peter; Panyi, Gyorgy

2010-05-01

380

Autoimmune Hepatitis with Multiple Sclerosis and Graves Disease: Coincidence or Association?  

PubMed Central

Autoimmune hepatitis (AIH) is a generally progressive, chronic hepatitis of unknown cause that occurs in children and adults of all ages. It is associated with a variety of autoimmune conditions like thyroid disorders (Hashimoto and Graves disease), celiac disease and multiple sclerosis (MS). We report the case of a 61-year-old woman with MS (untreated) and a history of Graves disease who presented with fatigue and right upper quadrant abdominal pain. She was admitted to our hospital for evaluation. Clinical and laboratory workup revealed AIH. She was successfully treated with prednisone and azathioprine, with complete clinical and laboratory improvement. However, to our knowledge there have been only a few reports of a possible association between AIH and untreated MS. PMID:25473390

Nadhem, Omar N.; Janabi, Mohammed Al; Omer, Abdel Rahman; Wan, Bang

2014-01-01

381

Enhanced proinflammatory state and autoimmune activation: a breakthrough to understanding chronic diseases.  

PubMed

Insight is provided herein into the novel mechanisms of cardiometabolic risk. Previous reports, including the epidemiological work of the Turkish Adult Risk Factor study, indicated that proinflammatory state and oxidative stress are crucial for evaluating cardiometabolic risk. Autoimmune pathways in the course of oxidative stress are major determinants of cardiorenal and metabolic risk. The latter encompasses metabolic syndrome, type 2 diabetes, coronary heart disease, and chronic kidney disease (CKD). Along with platelet-activating factor acetylhydrolase, creatinine, thyroid stimulating hormone, acylation-stimulating protein, asymmetric dimethylarginine, and serum lipoprotein[Lp](a) are triggers of systemic low-grade inflammation and enhanced autoimmune reactions. Related studies are analyzed in the current review. Lp(a) plays a crucial role by taking part in the immune activation, thereby accelerating the course of diabetes, CKD, and other chronic disorders. Populations prone to impaired glucose tolerance, and particularly peri- and postmenopausal women, are at high risk of developing related vascular complications. PMID:23565630

Onat, Altan; Can, Günay

2014-01-01

382

[Tiredness, hyperpigmentation, weight loss, nausea and vomiting. Polyglandular autoimmune syndrome (PAS) type 2].  

PubMed

In this patient with tiredness, hyperpigmentation, weight loss, nausea and vomiting, chronic primary adrenal insufficiency (M. Addison) was diagnosed based on the clinical features, the typical electrolyte abnormalities and the reduced morning cortisol together with increased adrenocorticotropic hormone. The detection of autoantibodies against adrenal tissue and 21-hydroxylase revealed an auto-immune adrenalitis as the cause. The additional primary hypothyroidism (with positive thyreoperoxidase-anti-bodies, anti-TPO-antibodies) and the coeliac disease argued for a polyglandular autoimmune syndrome type 2. Treatment with hydrocortisone and with mineralocorticoid and thyroxine later on showed a rapid improvement of clinical symptoms. In patients with Morbus Addison, a screening for associated endocrine disorders is warranted. PMID:20931500

Locher, Rebecca; Kohler, S; Schwanda, S; Schmid, C

2010-10-01

383

Janus-like effects of type I interferon in autoimmune diseases  

PubMed Central

Summary In multiple sclerosis, type I interferon (IFN) is considered immune-modulatory, and recombinant forms of IFN-? are the most prescribed treatment for this disease. This is in contrast to most other autoimmune disorders, since type I IFN contributes to the pathologies. Even within the relapsing-remitting multiple sclerosis (RRMS) population, 30–50% of MS patients are nonresponsive to this treatment and it consistently worsens neuromyelitis optica (NMO), a disease similar to RRMS. In this article, we discuss the recent advances in the field of autoimmunity and introduce the theory explain how type I IFNs can be pro-inflammatory in disease that is predominantly driven by a Th17 response and are therapeutic when disease is predominantly Th1. PMID:22725952

Axtell, Robert C.; Raman, Chander

2012-01-01

384

Cold Urticaria, Immunodeficiency, and Autoimmunity Related to PLCG2 Deletions  

PubMed Central

Background Mendelian analysis of disorders of immune regulation can provide insight into molecular pathways associated with host defense and immune tolerance. Methods We identified three families with a dominantly inherited complex of cold-induced urticaria, antibody deficiency, and susceptibility to infection and autoimmunity. Immunophenotyping methods included flow cytometry, analysis of serum immunoglobulins and autoantibodies, lymphocyte stimulation, and enzymatic assays. Genetic studies included linkage analysis, targeted Sanger sequencing, and next-generation whole-genome sequencing. Results Cold urticaria occurred in all affected subjects. Other, variable manifestations included atopy, granulomatous rash, autoimmune thyroiditis, the presence of antinuclear antibodies, sinopulmonary infections, and common variable immunodeficiency. Levels of serum IgM and IgA and circulating natural killer cells and class-switched memory B cells were reduced. Linkage analysis showed a 7-Mb candidate interval on chromosome 16q in one family, overlapping by 3.5 Mb a disease-associated haplotype in a smaller family. This interval includes PLCG2, encoding phospholipase C?2 (PLC?2), a signaling molecule expressed in B cells, natural killer cells, and mast cells. Sequencing of complementary DNA revealed heterozygous transcripts lacking exon 19 in two families and lacking exons 20 through 22 in a third family. Genomic sequencing identified three distinct in-frame deletions that cosegregated with disease. These deletions, located within a region encoding an autoinhibitory domain, result in protein products with constitutive phospholipase activity. PLCG2-expressing cells had diminished cellular signaling at 37°C but enhanced signaling at subphysiologic temperatures. Conclusions Genomic deletions in PLCG2 cause gain of PLC?2 function, leading to signaling abnormalities in multiple leukocyte subsets and a phenotype encompassing both excessive and deficient immune function. (Funded by the National Institutes of Health Intramural Research Programs and others.) PMID:22236196

Ombrello, Michael J.; Remmers, Elaine F.; Sun, Guangping; Freeman, Alexandra F.; Datta, Shrimati; Torabi-Parizi, Parizad; Subramanian, Naeha; Bunney, Tom D.; Baxendale, Rhona W.; Martins, Marta S.; Romberg, Neil; Komarow, Hirsh; Aksentijevich, Ivona; Kim, Hun Sik; Ho, Jason; Cruse, Glenn; Jung, Mi-Yeon; Gilfillan, Alasdair M.; Metcalfe, Dean D.; Nelson, Celeste; O'Brien, Michelle; Wisch, Laura; Stone, Kelly; Douek, Daniel C.; Gandhi, Chhavi; Wanderer, Alan A.; Lee, Hane; Nelson, Stanley F.; Shianna, Kevin V.; Cirulli, Elizabeth T.; Goldstein, David B.; Long, Eric O.; Moir, Susan; Meffre, Eric; Holland, Steven M.; Kastner, Daniel L.; Katan, Matilda; Hoffman, Hal M.; Milner, Joshua D.

2012-01-01

385

Autoimmune pancreatitis: Multimodality non-invasive imaging diagnosis.  

PubMed

Autoimmune pancreatitis (AIP) is characterized by obstructive jaundice, a dramatic clinical response to steroids and pathologically by a lymphoplasmacytic infiltrate, with or without a pancreatic mass. Type 1 AIP is the pancreatic manifestation of an IgG4-related systemic disease and is characterized by elevated IgG4 serum levels, infiltration of IgG4-positive plasma cells and extrapancreatic lesions. Type 2 AIP usually has none or very few IgG4-positive plasma cells, no serum IgG4 elevation and appears to be a pancreas-specific disorder without extrapancreatic involvement. AIP is diagnosed in approximately 2%-6% of patients that undergo pancreatic resection for suspected pancreatic cancer. There are three patterns of autoimmune pancreatitis: diffuse disease is the most common type, with a diffuse, "sausage-like" pancreatic enlargement with sharp margins and loss of the lobular contours; focal disease is less common and manifests as a focal mass, often within the pancreatic head, mimicking a pancreatic malignancy. Multifocal involvement can also occur. In this paper we describe the features of AIP at ultrasonography, computed tomography, magnetic resonance and positron emission tomography/computed tomography imaging, focusing on diagnosis and differential diagnosis with pancreatic ductal adenocarcinoma. It is of utmost importance to make an early correct differential diagnosis between these two diseases in order to identify the optimal therapeutic strategy and to avoid unnecessary laparotomy or pancreatic resection in AIP patients. Non-invasive imaging plays also an important role in therapy monitoring, in follow-up and in early identification of disease recurrence. PMID:25493001

Crosara, Stefano; D'Onofrio, Mirko; De Robertis, Riccardo; Demozzi, Emanuele; Canestrini, Stefano; Zamboni, Giulia; Pozzi Mucelli, Roberto

2014-12-01

386

Antibody titers predict clinical features of autoimmune autonomic ganglionopathy.  

PubMed

Autoimmune autonomic ganglionopathy is a disorder of isolated autonomic failure associated with antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia resulting in severe orthostatic intolerance, syncope, constipation, gastroparesis, urinary retention, dry mouth, dry eyes, blurred vision and anhidrosis. We report the autonomic test results, antibody titers and clinical findings in 8 patients with antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia. There was a sigmoidal relation between the antibody titers and the fall in systolic blood pressure (r(2)=0.84). The threshold occurred with antibody titers of approximately 1 nmol/l. Over the linear portion of the sigmoid curve, with antibody titers in the 1-3 nmol/l range, increasing antibody titers resulted in more severe orthostatic hypotension (r=0.94, P<0.001). The saturation point of the sigmoidal relation occurred at approximately 3 nmol/l with drops in systolic blood pressure of approximately 100 mmHg during upright tilt. The antibody titers correlated inversely with the Valsalva ratio (r=-0.87, P<0.001), the 30:15 ratio (r=-0.84, P<0.001) and the expiratory to inspiratory ratio (r=-0.67, P<0.01). Patients with orthostatic intolerance, anhidrosis, constipation, urinary dysfunction, sicca syndrome and pupillary dysfunction had higher antibody titers than subjects that did not (P<0.01 in all cases). Autoimmune autonomic ganglionopathy is a clinically heterogeneous disease with variable presentation, particularly in subjects with lower antibody titers. Our data suggest that patients with higher antibody titers have wide spread dysautonomia while those with lower antibody levels may present with, or evolve into, more focal or restricted presentations. PMID:19144572

Gibbons, Christopher H; Freeman, Roy

2009-03-12

387

Monogenic Autoimmune Diseases: Insights into Self-Tolerance  

PubMed Central

Autoimmune diseases affect a significant segment of the population and are typically thought to be multifactorial in etiology. Autoimmune diseases due to single gene defects are rare, but offer an invaluable window into understanding how defects in the immune system can lead to autoimmunity. In this review, we will focus on autoimmune polyendocrinopathy syndrome type 1 and recent advances in our understanding of this disease. We will also discuss two other monogenic autoimmune diseases: immunodysregulation, polyendocrinopathy, and enteropathy, X-linked and Autoimmune lymphoproliferative syndrome. Importantly, the knowledge and principles gained from studying these diseases have been applicable to more common autoimmune diseases and have opened the door to better diagnostic and therapeutic modalities. PMID:19190526

SU, MAUREEN A.; ANDERSON, MARK S.

2010-01-01

388

The PANDAS subgroup of tic disorders and childhood-onset obsessive–compulsive disorder  

Microsoft Academic Search

Diagnosis and treatment of the PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) variant of Gilles de la Tourette syndrome (GTS) and childhood-onset obsessive–compulsive disorder (OCD) are still controversial issues. Most cross-sectional studies confirm a significant association between GTS and the development of an immune response against group A ?-hemolytic streptococcus (GABHS). Moreover, longitudinal retrospective studies suggest that a

Davide Martino; Giovanni Defazio; Gavin Giovannoni

2009-01-01

389

The CD45 77C/G allele is not associated with myasthenia gravis - a reassessment of the potential role of CD45 in autoimmunity  

PubMed Central

Background The G allele of the CD45 77C/G SNP (rs17612648), which has previously been suggested to be associated with autoimmune disorders, was genotyped in 446 Swedish myasthenia gravis (MG) patients and 2303 matched controls. Results There was no association between the polymorphism and patient group as a whole (p = 0.199), nor with clinical subgroups. Our results add to a growing number of studies unable to find association between the 77C/G polymorphism and autoimmune disorders. One control sample, from an adult blood donor, was homozygous for the G allele, yet negative for a panel of auto-antibodies, representing the first homozygous individual studied in this respect. Conclusions The 77C/G mutation does not predispose to MG, and its role in autoimmunity may have to be re-evaluated. PMID:21067564

2010-01-01

390

A Unique Manifestation of Pupillary Fatigue in Autoimmune Autonomic Ganglionopathy  

PubMed Central

Objective To demonstrate a unique abnormality of the pupillary light reflex in patients with Autoimmune Autonomic Ganglionopathy (AAG). Design Case series Setting Autonomic clinics at two university hospitals (University of Texas Southwestern Medical Center and Beth Israel Deaconess Medical Center) Participants Seven patients with antibody positive AAG. Intervention All patients with AAG underwent either monocular or binocular infrared pupillometry using a standard 2 second light stimulus at a defined intensity. Findings were compared to healthy controls and patients with other autonomic disorders. The light stimulus used in this study was selected to eliminate the normal phenomenon of pupil escape. Main Outcome measure The time to onset of redilation was the main outcome measure. Other indices of pupillary constriction to light stimulus were also measured. Results Patients with AAG exhibited premature pupillary redilation (1.02 ±0.20 seconds) compared to healthy control subjects (2.24±0.10 seconds) and other patients with autonomic disorders (2.3±0.12 seconds; P<0.0001). In healthy control subjects and patients with other autonomic disorders pupillary redilation always followed the termination of the light stimulus while in AAG patients redilation consistently occurred during the light stimulus. In one patient, serial repetitive light stimulation further decreased the time to onset of redilation. Conclusion Premature redilation of the pupil is a unique physiological feature seen only in patients with AAG. This phenomenon appears to be a manifestation of pupillary fatigue, a clinical correlate of defective synaptic transmission at the level of autonomic ganglia in antibody positive AAG. PMID:22232207

Muppidi, Srikanth; Scribner, Maggie; Gibbons, Christopher H.; Adams-Huet, Beverley; Spaeth, Elaine B.; Vernino, Steven

2012-01-01

391

Total lymphoid irradiation in alloimmunity and autoimmunity  

SciTech Connect

Total lymphoid irradiation has been used as an immunosuppressive regimen in autoimmune disease and organ transplantation. The rationale for its use originated from studies of patients with Hodgkin disease, in whom this radiotherapy regimen was noted to induce profound and long-lasting immune suppression and yet was well tolerated, with few long-term side effects. Total lymphoid irradiation is a unique immunosuppressive regimen that produces a selective (and long-lasting) reduction in the number and function of helper T cells and certain subsets of B cells. Conventional immunosuppressive drugs show little selectivity, and their effects are short-lived. The most important aspect of total lymphoid irradiation is the potential for achieving transplantation tolerance and permanent remissions in autoimmune disease in laboratory animals. Attempts are being made to achieve similar goals in humans given total lymphoid irradiation, so that immunosuppressive drugs can be ultimately withdrawn from transplant recipients and patients with lupus nephritis. 28 references.

Strober, S.

1987-12-01

392

The mechanisms behind helminth's immunomodulation in autoimmunity.  

PubMed

The incidence of autoimmune diseases has risen throughout the last half a century, mostly in the industrialized world. Helminths and their derivatives were found to have a protective role in autoimmunity and inflammatory conditions, as they manipulate the immune network, attenuating the host's cellular and humoral responses. Indeed, various helminth species used in several human and animal models were shown to limit inflammatory activity in a variety of diseases including inflammatory bowel disease, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis. Our review will focus on the main mechanisms by which helminths and their secreted molecules modulate the host's immune system. The main pathways induce a shift from Th1 to Th2 phenotype, accelerate T regulatory and B regulatory phenotypes, and attenuate the levels of the inflammatory cytokines, leading to a tolerable scenario. PMID:25449677

Bashi, Tomer; Bizzaro, Giorgia; Ben-Ami Shor, Dana; Blank, Miri; Shoenfeld, Yehuda

2015-02-01

393

THE CONSEQUENCES OF APOPTOSIS IN AUTOIMMUNITY  

PubMed Central

The clearance of apoptotic cells is a highly regulated mechanism, normally associated with anti-inflammatory response. During early stages of apoptosis the cell is promptly recognized and engulfed by professional phagocytes or tissue cells to avoid the outflow of intracellular content and limit the immunological reaction against released antigens. However, increasing evidences suggest that impairment in the uptake of apoptotic cell debris is linked to the development of autoimmunity. In fact, autoantigens have been demonstrated to be content within apoptotic bodies and apoptotic cells seems to be critical in the presentation of antigens, activation of innate immunity and regulation of macrophage cytokine secretion. We herein review the known mechanisms for regulating the uptake of the products of apoptosis in the development of autoimmunity. PMID:18513925

Lleo, Ana; Selmi, Carlo; Invernizzi, Pietro; Podda, Mauro; Gershwin, M. Eric

2008-01-01

394

Fragile privileges: autoimmunity in brain and eye  

PubMed Central

Brain and eye tissues are subject to a reduced version of immune surveillance, which has evolved to protect the particularly sensitive tissues from accidental bystander damage created by regular inflammatory responses. Yet, there are autoimmune diseases in both organs. This review discusses the nature of immune reactivity in the healthy eye and brain tissues, and mechanisms that can overcome the protective barriers to create tissue specific disease. PMID:20818330

Wekerle, Hartmut; Sun, De-ming

2010-01-01

395

Autoimmune thyroid disease in ankylosing spondylitis.  

PubMed

Although autoimmune thyroid disease is well known to be associated with primary Sjögren's syndrome (SjS) and with various autoimmune diseases, it is less clear whether a similar association also exists for ankylosing spondylitis (AS). Therefore, we investigated the frequency of autoimmune thyroid disease in patients with AS. In this cross sectional study, 80 patients with AS fulfilling the 1984 Modified New York Criteria and 80 healthy subjects, age and sex-matched with AS patients, were included. As the positive control group, 62 female patients with primary SjS were also studied. All cases underwent thyroid ultrasonography (USG) by a single endocrinologist. Thyroid function tests and thyroid autoantibodies were measured. The diagnosis of Hashimoto's thyroiditis (HT) was made if the patient had thyroid autoantibody positivity plus at least one of the following criteria: diffuse goiter with physical examination, abnormality in thyroid function tests, and parenchymal heterogeneity with USG. The chi-squared test and Fisher's exact test were used to compare cases and controls. The p values <0.05 were considered statistically significant. The frequencies of parenchymal heterogeneity with USG (30 vs 11.3 %, p?=?0.045), thyroid autoantibody positivity (13.8 vs 2.5 %, p?=?0.017), and concomitant diagnosis of HT (10 vs 1.3 %, p?=?0.034) were significantly higher in AS group compared to healthy controls. Among AS patients having HT, subclinical hypothyroidism was detected only in a single patient. Frequency of autoimmune thyroid disease was significantly higher in AS group, compared to healthy controls. Prospective studies are needed to see the clinical relevance of these findings and outcome in the long term. PMID:24384825

Emmungil, Hakan; Erdogan, Mehmet; Kalfa, Melike; Karabulut, Gonca; Kocanaogullar?, Hayriye; Inal, Vedat; Aksu, Kenan; Oksel, Fahrettin; Kabasakal, Yasemin; Keser, Gokhan

2014-07-01

396

Oral Tolerance: Therapeutic Implications for Autoimmune Diseases  

PubMed Central

Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10) and Th3 (TGF-?) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-?, cholera toxin B subunit (CTB), Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE), uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy and early therapy. PMID:17162357

Faria, Ana M. C.; Weiner, Howard L.

2006-01-01

397

Development of outcome measures for autoimmune dermatoses  

Microsoft Academic Search

Validated outcome measures are essential in monitoring disease severity. Specifically in dermatology, which relies heavily\\u000a on the clinical evaluation of the patient and not on laboratory values and radiographic tests, outcome measures help standardize\\u000a patient care. Validated cutaneous scoring systems, much like standardized laboratory values, facilitate disease management\\u000a and follow therapeutic response. Several cutaneous autoimmune dermatoses, specifically cutaneous lupus erythematosus

Elizabeth Gaines; Victoria P. Werth

2008-01-01

398

Experimental Autoimmune Encephalomyelitis in the Rat Spinal Cord: Lesion Detection with High-Resolution MR Microscopy at 17.6 T  

Microsoft Academic Search

BACKGROUND AND PURPOSE: Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disorder of the CNS and an animal model of multiple sclerosis. We used high-field MR microscopy at 17.6 T to image spinal cord inflammatory lesions in the acute stage of chronic relapsing rat EAE. We sought to compare lesions detected on MR imaging with histopathologic findings and to quantify

Andreas Steinbrecher; Thomas Weber; Thomas Neuberger; Xiomara Pedre; Gerhard Giegerich; Ulrich Bogdahn; Peter Jakob; Axel Haase; Cornelius Faber

399

Mechanisms of IFN? regulation of autoimmune myocarditis  

PubMed Central

A protective effect of interferon-gamma (IFN?) has been described in a number of models of autoimmune disease, including experimental autoimmune myocarditis (EAM). Some reports have suggested that regulation of apoptosis in autoreactive lymphocytes mediate these protective functions. We examined the potential of IFN? to regulate apoptotic mechanisms in detail, both in vitro and in vivo in EAM. We observed multiple apoptotic defects in caspase activity, and the expression of TNF superfamily members on CD4+ T cells. In addition, we observed selective defects in CD4+ T cell activation in response to antigenic stimulation. These activation and apoptotic defects were CD4+ cell autonomous, independent of the genotype of APCs. Inhibition of nitric oxide production in vivo did not reproduce the severe form of EAM of IFN?-deficient mice, indicating that this pathway does not mediate the protective effect of IFN?. Crosswise adoptive transfer of wild type, IFN??/?, and IFN?R?/? EAM demonstrated that IFN? signaling was critical in CD4+ cells, but that non-CD4+ sources of IFN? production were also involved in the control of disease. Together, these data indicate multiple mechanisms of autonomous and non-autonomous CD4+ T cell regulation mediated by IFN? in the control of autoimmune heart disease. PMID:20599938

Barin, Jobert G.; Talor, Monica V.; Baldeviano, G. Christian; Kimura, Miho; Rose, Noel R.; ?iháková, Daniela

2014-01-01

400

Pathophysiology of inflammatory and autoimmune myopathies.  

PubMed

The main subtypes of inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion-body myositis (sIBM). The review provides an update on the main clinical characteristics unique to each subset, including fundamental aspects on muscle pathology helpful to assure accurate diagnosis, underlying immunopathomechanisms and therapeutic strategies. DM is a complement-mediated microangiopathy leading to destruction of capillaries, distal hypoperfusion and inflammatory cell stress on the perifascicular regions. NAM is an increasingly recognized subacute myopathy triggered by statins, viral infections, cancer or autoimmunity with macrophages as the final effector cells mediating fiber injury. PM and IBM are characterized by cytotoxic CD8-positive T cells which clonally expand in situ and invade MHC-I-expressing muscle fibers. In IBM, in addition to autoimmunity, there is vacuolization and intrafiber accumulation of degenerative and stressor molecules. Pro-inflammatory mediators, such as gamma interferon and interleukin IL1-?, seem to enhance the accumulation of stressor and amyloid-related misfolded proteins. Current therapies using various immunosuppressive and immunomodulating drugs are discussed for PM, DM and NAM, and the principles for effective treatment strategies in IBM are outlined. PMID:21411269

Dalakas, Marinos C

2011-04-01

401

The Dopaminergic System in Autoimmune Diseases  

PubMed Central

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

Pacheco, Rodrigo; Contreras, Francisco; Zouali, Moncef

2014-01-01

402

Immunotherapy Treatments of Warm Autoimmune Hemolytic Anemia  

PubMed Central

Warm autoimmune hemolytic anemia (WAIHA) is one of four clinical types of autoimmune hemolytic anemia (AIHA), with the characteristics of autoantibodies maximally active at body temperature. It produces a variable anemia—sometimes mild and sometimes severe. With respect to the absence or presence of an underlying condition, WAIHA is either idiopathic (primary) or secondary, which determines the treatment strategies in practice. Conventional treatments include immune suppression with corticosteroids and, in some cases, splenectomy. In recent years, the number of clinical studies with monoclonal antibodies and immunosuppressants in the treatment of WAIHA increased as the knowledge of autoimmunity mechanisms extended. This thread of developing new tools of treating WAIHA is well exemplified with the success in using anti-CD20 monoclonal antibody, Rituximab. Following this success, other treatment methods based on the immune mechanisms of WAIHA have emerged. We reviewed these newly developed immunotherapy treatments here in order to provide the clinicians with more options in selecting the best therapy for patients with WAIHA, hoping to stimulate researchers to find more novel immunotherapy strategies. PMID:24106518

Gu, Wangang

2013-01-01

403

Experimental autoimmune myasthenia gravis in the mouse  

PubMed Central

Myasthenia gravis (MG) is a T cell-dependent antibody-mediated autoimmune neuromuscular disease. Antibodies to the nicotinic acetylcholine receptor (AChR) destroy the AChR, thus leading to defective neuromuscular transmission of electrical impulse and to muscle weakness. This unit is a practical guide to the induction and evaluation of experimental autoimmune myasthenia gravis (EAMG) in the mouse, the animal model for MG. Protocols are provided for the extraction and purification of AChR from the electric organs of Torpedo californica, or eel. The purified receptor is used as an immunogen to induce autoimmunity to AChR, thus causing EAMG. The defect in neuromuscular transmission can also be measured quantitatively by electromyography. In addition, EAMG is frequently characterized by the presence of serum antibodies to AChR, which are measured by radioimmunoassay and by a marked antibody-mediated reduction in the number of muscle AChRs. AChR extracted from mouse muscle is used in measuring serum antibody levels and for quantifying muscle AChR content. Another hallmark of the disease is complement and IgG deposits located at the neuromuscular junction, which can be visualized by immunofluorescence techniques. PMID:18432738

Wu, Bo; Goluszko, Elzbieta; Huda, Ruksana; Tuzun, Erdem; Christadoss, Premkumar

2011-01-01

404

Oral zinc aspartate treats experimental autoimmune encephalomyelitis.  

PubMed

The essential trace element zinc plays a critical role in the regulation of immune homeostasis. Zinc deficiency or excess can cause severe impairment of the immune response, which points to the importance of the physiological and dietary control of zinc levels for a functioning immune system. We previously reported that injection of zinc aspartate suppresses experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), as well as effector T cell functions in vitro. Among the preferred characteristics of novel therapeutics for the treatment of autoimmune diseases such as MS are oral availability and a tolerable effective dose to minimize side effects. In this study, we investigated whether oral administration of zinc aspartate, an approved drug to treat zinc deficiency in humans, is effective in controlling EAE at clinically approved doses. We show that oral administration of 6 µg/day [0.3 mg/kg body weight (BW)] or 12 µg/day [0.6 mg/kg BW] of zinc aspartate reduces clinical and histopathological signs during the relapsing remitting phase of the disease in SJL mice. The clinical effect in mice was accompanied by suppression of IFN-?, TNF-?, GM-CSF and IL-5 production in stimulated human T cells and mouse splenocytes in a dose-dependent manner. Furthermore, a large array of proinflammatory cytokines was modulated by zinc aspartate exposure in vitro. These data suggest that administration of oral zinc aspartate may have beneficial effects on autoimmune diseases like MS. PMID:25146336

Schubert, Claudia; Guttek, Karina; Grüngreiff, Kurt; Thielitz, Anja; Bühling, Frank; Reinhold, Annegret; Brocke, Stefan; Reinhold, Dirk

2014-12-01

405

PRENATAL TCDD IN MICE INCREASES ADULT AUTOIMMUNITY  

PubMed Central

Two immunologically-different mouse strains, C57BL/6 and SNF1, were exposed to a mid-gestation dose of TCDD. The C57BL/6 mouse has a high-affinity aryl hydrocarbon receptor (AhR) and is sensitive to TCDD. The SNF1 mouse has a low-affinity AhR but spontaneously develops autoimmune nephritis. Autoreactive V?+CD4+17a and V?+CD3+ T cells were increased at 24-weeks-of-age in offspring of C57BL/6 mice, more so in females than males. The cytokine IFN-? was elevated in the females, while IL-10 was elevated in males. Phenotypic changes in B-lineage cells were present in bone marrow and spleen, and circulating autoantibodies were increased after prenatal TCDD. Kidneys of males showed significant anti-IgG and anti-C3 deposition, suggesting early-stage autoimmune disease. The SNF1 offspring similarly showed increased peripheral V?+ cells in the females, increased autoantibody production in both sexes, and increased IFN-? production in females. Male SNF1 mice had increased anti-IgG and anti-C3 deposition in kidneys. Both mouse models therefore showed clear signatures of enhanced autoimmunity after prenatal TCDD. PMID:20728533

Holladay, Steven D.; Gogal, Robert M.

2010-01-01

406

Interleukin-32 in Inflammatory Autoimmune Diseases  

PubMed Central

Interleukin-32 (IL-32) is a cytokine inducing crucial inflammatory cytokines such as tumor necrosis factor-? (TNF?) and IL-6 and its expression is elevated in various inflammatory autoimmune diseases, certain cancers, as well as viral infections. IL-32 gene was first cloned from activated T cells, however IL-32 expression was also found in other immune cells and non-immune cells. IL-32 gene was identified in most mammals except rodents. It is transcribed as multiple-spliced variants in the absence of a specific activity of each isoform. IL-32 has been studied mostly in clinical fields such as infection, autoimmune, cancer, vascular disease, and pulmonary diseases. It is difficult to investigate the precise role of IL-32 in vivo due to the absence of IL-32 gene in mouse. The lack of mouse IL-32 gene restricts in vivo studies and restrains further development of IL-32 research in clinical applications although IL-32 new cytokine getting a spotlight as an immune regulatory molecule processing important roles in autoimmune, infection, and cancer. In this review, we discuss the regulation and function of IL-32 in inflammatory bowel diseases and rheumatoid arthritis. PMID:24999308

2014-01-01

407

Arthritogenic T cells in autoimmune arthritis.  

PubMed

Autoimmune diseases, including arthritis, often result from an imbalance between regulatory T (Treg) cells and IL-17-producing (Th17) cells. Dozens of studies in mice and humans have shed light on the pathological significance of T cells in RA. Since Th17 cells play an important role in the exacerbation of inflammation and bone destruction in joints, it has been an important issue how arthritic Th17 cells arise. Th17 cells are generated in the local inflammatory milieu via cytokines produced by macrophages or synovial fibroblasts, while it is reported that Th17 cells are generated in the gut in the presence of specific commensal bacteria. A recent report showed a pathogenic Th17 cell subset with a distinct pattern of gene expression and a potent osteoclastogenic ability are converted from Foxp3(+) T cells in arthritic joints. Since Foxp3(+) Treg cells contain T cells which recognize self-antigens, the fate of plastic Foxp3(+) T cells can be a critical determinant of autoimmunity or self-tolerance. Further analysis on the molecular basis and antigen-specificity of arthritogenic Th17 cell subsets will be helpful to establish novel therapeutic approaches and clarify how self-tolerance breaks down in autoimmune arthritis. PMID:25450406

Komatsu, Noriko; Takayanagi, Hiroshi

2015-01-01

408

Virus-driven autoimmunity and lymphoproliferation: the example of HCV infection.  

PubMed

HCV chronic infection is characterized by possible development of both hepatic and extrahepatic manifestations. The infection by this both hepatotropic and lymphotropic virus is responsible for polyoligoclonal B-lymphocyte expansion, leading to several immune-mediated disorders. Mixed cryoglobulinemia syndrome that in some cases may evolve to frank B-cell non-Hodgkin's lymphoma is the prototype of HCV-driven autoimmune and lymphoproliferative disorders. The HCV oncogenic potential has been suggested by several clinicoepidemiological and laboratory studies; it includes hepatocellular carcinoma, B-cell non-Hodgkin's lymphoma and papillary thyroid cancer. The definition HCV syndrome refers to the complex of HCV-driven diseases; these latter are characterized by heterogeneous geographical distribution, suggesting a role of other important genetic and/or environmental cofactors. The natural history of HCV syndrome is the result of a multifactorial and multistep pathogenetic process, which may evolve from mild manifestations to systemic autoimmune disorders, and less frequently to malignant neoplasias. The present updated review analyzes the clinical and pathogenetic aspects of the main HCV-associated diseases. PMID:25534977

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

2015-01-01

409

Severe Autoimmune Polyendocrinopathy-Candidiasis- Ectodermal Dystrophy in an Adolescent Girl with a Novel AIRE Mutation: Response to Immunosuppressive Therapy  

Microsoft Academic Search

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystro- phy (APECED) is a rare autosomal recessive disorder for which the gene (AIRE) has recently been identified on chromosome 21q22.3. We present the mutational analyses of a French-Canadian family with APECED, in which there are two affected siblings, as well as the response to cyclosporine A(CyA) therapy in the index patient, the eldest sibling. Haplotype analysis suggested

LEANNE WARD; JEAN PAQUETTE; ERNEST SEIDMAN; CELINE HUOT; FERNANDO ALVAREZ; PATRICIA CROCK; EDGARD DELVIN; OLLE KAMPE; CHERI DEAL

2010-01-01

410

No Evidence of Autoimmunity in 6YearOld Children Immunized at Birth With Recombinant Hepatitis B Vaccine  

Microsoft Academic Search

ABSTRACT. Objectives. Taking into account that ge- netic predisposition, marked by human leukocyte anti- gen (HLA) class I and II genes, augments the probability of developing an autoimmune disorder after a triggering vaccination, as largely debated, we investigated the fre- quency of autoantibody production after recombinant hepatitis B vaccine (rHBv) in 6-year-old children immu- nized at birth to evaluate an

Cesare Belloni; Maria A. Avanzini; Annalisa De Silvestri; Miryam Martinetti; Annamaria Pasi; Eliana Coslovich; Michele Autelli; Maria L. Masanti

411

Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines  

Microsoft Academic Search

Newly licensed vaccines against human papillomavirus (HPV) and hepatitis B (HBV), and several vaccines in development, including a vaccine against genital herpes simplex virus (HSV), contain a novel Adjuvant System, AS04, composed of 3-O-desacyl-4? monophosphoryl lipid A and aluminium salts. Given the background incidence of autoimmune disorders in some of the groups targeted for immunisation with these vaccines, it is

Thomas Verstraeten; Dominique Descamps; Marie-Pierre David; Toufik Zahaf; Karin Hardt; Patricia Izurieta; Gary Dubin; Thomas Breuer

2008-01-01

412

Resistance to CpG DNA–induced autoimmunity through tolerogenic B cell antigen receptor ERK signaling  

Microsoft Academic Search

CpG sequences in self-DNA are an important potential trigger for autoantibody secretion in systemic lupus and other systemic autoimmune disorders. It is not known how this ubiquitous threat may be controlled by active mechanisms for maintaining self tolerance. Here we show that two distinct mechanisms oppose autoantibody se