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1

Autoimmune disorders  

MedlinePLUS

... hormone, vitamin B12, or insulin, due to the autoimmune disease Blood transfusions if blood is affected Physical therapy ... The outcome depends on the disease. Most autoimmune diseases are chronic ... disorders can come and go. When symptoms get worse, it is ...

2

Autoimmune Thyroid Disorders  

PubMed Central

Purpose of Review. Studies have been published in the field of autoimmune thyroid diseases since January 2005. The review is organized into areas of etiology, autoimmune features, autoantibodies, mechanism of thyroid cell injury, B-cell responses, and T-cell responses. Also it reviews the diagnosis and the relationship between autoimmune thyroid disease, neoplasm, and kidney disorders. Recent Findings. Autoimmune thyroid diseases have been reported in people living in different parts of the world including North America, Europe, Baalkans, Asia, Middle East, South America, and Africa though the reported figures do not fully reflect the number of people infected per year. Cases are unrecognized due to inaccurate diagnosis and hence are treated as other diseases. However, the most recent studies have shown that the human autoimmune thyroid diseases (AITDs) affect up to 5% of the general population and are seen mostly in women between 30 and 50 years. Summary. Autoimmune thyroid disease is the result of a complex interaction between genetic and environmental factors. Overall, this review has expanded our understanding of the mechanism involved in pathogenesis of AITD and the relationship between autoimmune thyroid disease, neoplasm, and kidney disease. It has opened new lines of investigations that will ultimately result in a better clinical practice. PMID:23878745

Iddah, M. A.; Macharia, B. N.

2013-01-01

3

Systemic inflammatory and autoimmune disorders.  

PubMed

Systemic disorders with possible involvement of the nervous system include a variety of diseases with presumed inflammatory and autoimmune pathomechanisms, among them Behçet disease, sarcoidosis, systemic lupus erythematosus, juvenile idiopathic arthritis, scleroderma, and Sjögren syndrome. This disease group encompasses systemic inflammatory disorders with a genetically defined dysregulation of the innate immune system as well as systemic autoimmune disorders characterized by alterations of the adaptive immunity such as autoantibodies and autoreactive T cells. Although more commonly diagnosed in adults, all of these diseases can manifest in childhood and some as early as infancy. Neurological involvement may represent the initial manifestation, and nearly every neurological symptom can be caused by inflammatory/autoimmune diseases. In a child with (sub)acute onset of otherwise unexplained neurological findings, consideration of inflammatory/autoimmune disorders may be of crucial therapeutic and prognostic importance. In the absence of disease-specific clinical features, the initial diagnostic workup is broad. Basic blood tests include inflammatory markers and autoantibodies. Cerebral magnetic resonance imaging and a lumbar puncture with measurement of opening pressure as well as cerebrospinal fluid analysis are indicated in most patients with central nervous system (CNS) involvement. Skin, muscle, or organ biopsies (e.g., renal) may provide additional information. Especially in patients with isolated CNS involvement, a brain biopsy may be indicated. Timely recognition and treatment of CNS inflammation may improve or even reverse clinical symptoms and prevent secondary brain injury. PMID:23622335

Pohl, Daniela; Benseler, Susanne

2013-01-01

4

Celiac sprue: a unique autoimmune disorder  

PubMed Central

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

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

2011-01-01

5

Humoral and Cellular Autoimmunity in Autoimmune Bullous Skin Disorders  

Microsoft Academic Search

Autoimmune bullous skin diseases, such as pemphigus vulgaris (PV) and bullous pemphigoid (BP), are severe, frequently life-threatening skin disorders. Immunologically, they are characterized by the presence of serum autoantibodies (auto-Ab) targeting distinct adhesion molecules of the epidermis or dermoepidermal basement membrane zone. Antibody (Ab) binding interferes with the adhesive function of these molecules, leading to detachment and subsequently blister formation.

Michael Hertl

2000-01-01

6

Celiac Disease and Autoimmune Endocrinologic Disorders  

Microsoft Academic Search

Patients with insulin-dependent diabetesmellitus, autoimmune thyroid disease, Addison's disease,and alopecia areata are at increased risk of celiacdisease. We investigated whether patients with more than one autoimmune endocrinologic disorder areeven more susceptible to celiac disease or haveceliac-type mucosal inflammation. All 62 patients foundto have such multiple diseases in 1994-1996 were investigated. Small bowel biopsy was performedon all voluntary nonceliac subjects. The

Katri Kaukinen; Pekka Collin; Anna-Helena Mykkanen; Jukka Partanen; Markku Maki; Jorma Salmi

1999-01-01

7

[Bullous autoimmune disorders in children].  

PubMed

We review the pathogenesis, clinical features, diagnosis, differential diagnosis, and therapy of autoimmune bullous skin diseases of childhood, especially of the most common linear IgA dermatosis. In autoimmune bullous diseases, autoantibodies are formed against different adhesion molecules of the skin. These are not only pathophysiologically relevant, but also serve as basis for diagnosis and follow-up of these diseases. In case an autoimmune bullous disease is suspected, histopathology and immunohistopathology (direct immunofluorescence microscopy) as well as serological tests (indirect immunofluorescence microscopy, ELISA, immunoblot) should be performed. Therapy depends on the diagnosis. In IgA-mediated pathogenesis, dapsone can be successfully used. In IgG-mediated diseases, immunosuppression with corticosteroids and steroid-sparing agents should be initiated, although only local therapy is sufficient to control a self-limiting pemphigus neonatorum. In dermatitis herpetiformis, a life-long gluten-free diet is recommended. PMID:23677541

Sárdy, M; Kasperkiewicz, M

2013-06-01

8

Epilepsy Associated with Systemic Autoimmune Disorders  

PubMed Central

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

2013-01-01

9

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

10

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

PubMed

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

Hoekstra, Pieter J; Minderaa, Ruud B

2005-12-01

11

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

12

Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used  

Microsoft Academic Search

Patients undergoing autologous hemato- poietic stem cell transplantation (auto- HSCT) for autoimmune disease may have an added propensity to develop a second autoimmune disorder, given the genetic predisposition to autoimmunity. There- fore, we undertook a retrospective analy- sis of all patients who have undergone auto-HSCT for an autoimmune disease in our institution to determine the occur- rence of a second

Yvonne Loh; Yu Oyama; Laisvyde Statkute; Kathleen Quigley; Kimberly Yaung; Elizabeth Gonda; Walter Barr; Borko Jovanovic; Robert Craig; Dusan Stefoski; Bruce Cohen; Richard K. Burt

2007-01-01

13

Autoimmune Hepatitis  

MedlinePLUS

... with type 1 autoimmune hepatitis commonly have other autoimmune disorders, such as celiac disease, an autoimmune disease in ... 2 can also have any of the above autoimmune disorders. [ Top ] What are the symptoms of autoimmune hepatitis? ...

14

Rituximab in Treatment-Resistant Autoimmune Blistering Skin Disorders  

Microsoft Academic Search

Autoimmune blistering diseases are associated with autoantibodies to desmosomal (pemphigus group) or hemidesmosomal proteins\\u000a (autoimmune subepidermal blistering disorders) that are essential for the structural integrity of the epidermis and dermoepidermal\\u000a junction. Treatment is usually based on systemic glucocorticosteroids, which are often combined with additional immunosuppressants\\u000a such as azathioprine and mycophenolate mofetil or immunomodulators including dapsone, antibiotics, and intravenous immunoglobulins.\\u000a These

Enno Schmidt; Eva-Bettina Bröcker; Matthias Goebeler

2008-01-01

15

Familial Clustering of Autoimmune Disorders and Evaluation of Medical Risk Factors in Autism  

Microsoft Academic Search

Autism is an age-dependent neurologic disorder that is often associated with autoimmune disorders in the patients' relatives. To evaluate the frequency of autoimmune disorders, as well as various prenatal and postnatal events in autism, we surveyed the families of 61 autistic patients and 46 healthy controls using questionnaires. The mean number of autoimmune disorders was greater in families with autism;

Anne M. Comi; Andrew W. Zimmerman; Virginia H. Frye; Paul A. Law; Joseph N. Peeden

1999-01-01

16

Celiac disease in autoimmune cholestatic liver disorders  

Microsoft Academic Search

OBJECTIVES:In this study, serological screening for celiac disease (CD) was performed in patients with autoimmune cholestasis to define the prevalence of such an association and to evaluate the impact of gluten withdrawal on liver disease associated with gluten sensitive enteropathy.METHODS:Immunoglobulin A endomysial, human and guinea pig tissue transglutaminase antibodies, and immunoglobulin A and G gliadin antibodies were sought in 255

Umberto Volta; Luis Rodrigo; Alessandro Granito; Nunzio Petrolini; Paolo Muratori; Luigi Muratori; Antonio Linares; Lorenza Veronesi; Dolores Fuentes; Daniela Zauli; Francesco B. Bianchi

2002-01-01

17

Genetics of autoimmune diseases — disorders of immune homeostasis  

Microsoft Academic Search

In the past few years, our extensive knowledge of the mammalian immune system and our increasing ability to understand the genetic causes of complex human disease have opened a window onto the pathways that lead to autoimmune disorders. In addition to the well-established role of genetic variation that affects the major histocompatibility complex, a number of rare and common variants

Timothy W. Behrens; Peter K. Gregersen

2006-01-01

18

Intravenous immunoglobulin (IVIG) for the therapy of autoimmune disorders  

Microsoft Academic Search

The weight of evidence from numerous clinical studies supports the use of IVIG, particularly at higher doses, in the treatment of a wide range of autoimmune disorders. Extensive experience has documented the safety of IVIG therapy but its present relatively high cost necessitates firmly establishing its efficacy. There is an acute need to define those disease states where IVIG is

Stanley A. Schwartz

1990-01-01

19

Narrative Review: Celiac Disease: Understanding a Complex Autoimmune Disorder  

Microsoft Academic Search

nce considered a rare childhood disorder, celiac dis- ease is now known to be a common condition that may have multiple complications. Nevertheless, the disease remains widely underrecognized. Use of new serologic markers in the diagnosis of celiac disease, in particular anti-transglutaminase antibody, has resulted in more effi- cient screening. Information on the pathogenic mechanism of the autoimmune response in

Armin Alaedini; Peter H. R. Green

2005-01-01

20

Eating Disorders: Could They be Autoimmune Diseases?  

Microsoft Academic Search

Summary Recent research on Anorexia Nervosa (AN) and Bulimia Nervosa (BN) has shown an increasing understanding of the biological and physiological abnormalities that underlie the development of an eating disorder. Cultural pressures, individual and family experiences, along with physiological and genetic systems all appear to contribute to the onset of these disorders. There is significant evidence for genetic factors in

Melissa Stevenson

2006-01-01

21

Calreticulin’s Role(s) in Autoimmune Disorders  

Microsoft Academic Search

\\u000a For over ten years autoantibodies (Aab) against calreticulin (CRT) have been reported in a number of autoimmune disorders\\u000a including rheumatoid arthritis, Sjögren’s syndrome, celiac disease and complete congenital heart block. The most studied group\\u000a is patients with systemic lupus erythematosus (SLE), where Aab against CRT have been detected in 40% of all patients. A number\\u000a of studies have sought to

Richard D. Sontheimer; Doina Racila; Emil Racila; Paul Eggleton; Suzanne Donnelly

22

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections  

PubMed Central

Abstract Question I have heard about children who have tic disorders that seem to be exacerbated by group A ?-hemolytic streptococcal infection. Should children presenting with this phenomenon receive treatment with antibiotics, receive prophylactic treatment, or use immunomodulators to treat the symptoms? Answer Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) constitute a condition that includes neuropsychiatric symptoms, mainly obsessive-compulsive disorder or tic disorders, temporally associated with an immune-mediated response to streptococcal infections. The actual existence of PANDAS as a unique clinical entity is still up for debate, as a temporal association between group A ?-hemolytic streptococcal infections and symptom exacerbations has been difficult to prove thus far. Based on only a few studies, positive results have been found using antibiotic prophylaxis and immunomodulatory therapy in children with PANDAS. At this time, however, evidence does not support a recommendation for long-term antibiotic prophylaxis or immunomodulatory therapy. PMID:22972724

Tan, Jason; Smith, Christine H.; Goldman, Ran D.

2012-01-01

23

Psychiatric Disorders in First-Degree Relatives of Children With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS)  

Microsoft Academic Search

ObjectiveTo determine the rates of psychiatric disorders in the first-degree relatives of children with infection-triggered obsessive-compulsive disorder (OCD) and\\/or tics (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; PANDAS).

LORRAINE LOUGEE; SUSAN J. PERLMUTTER; ROB NICOLSON; MARJORIE A. GARVEY; SUSAN E. SWEDO

2000-01-01

24

Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS).  

PubMed

The evidence to date, both published and unpublished, which addresses the validity of the proposed unique subgroup of children with early and abrupt onset of obsessive--compulsive disorder (OCD) and/or tic disorders subsequent to streptococcal infections was reviewed. The aetiology of OCD and tic disorders is unknown, although it appears that both disorders may arise from a variety of genetic and environmental factors. Post-streptococcal autoimmunity has been postulated as one possible mechanism for some. The acronym PANDAS (for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been given to a subgroup of paediatric patients who meet five inclusionary criteria: presence of OCD and/or tic disorder, pre-pubertal symptom onset, sudden onset or episodic course of symptoms, temporal association between streptococcal infections and neuropsychiatric symptom exacerbations, and associated neurological abnormalities. The proposed model of pathophysiology provides for several unique treatment strategies, including the use of antibiotic prophylaxis to prevent streptococcal-triggered exacerbations, and the use of immunomodulatory interventions (such as intravenous immunoglobulin or therapeutic plasma exchange) in the treatment severe neuropsychiatric symptoms. For the latter study group, long-term (2--5 yr) follow-up revealed continued symptom improvement for the majority of patients, particularly when antibiotic prophylaxis had been effective in preventing recurrent streptococcal infections. In addition, the episodic nature of the subgroup's illness provides for opportunities to study brain structure and function during health and disease, as well as allowing for investigations of the aetiologic role of anti-neuronal antibodies and neuroimmune dysfunction in both OCD and tic disorders. Although much research remains to be done, an increasing body of evidence provides support for the postulate that OCD and tic disorders may arise from post-streptococcal autoimmunity. The unique clinical characteristics of the PANDAS subgroup, the presence of volumetric changes in the basal ganglia, and the dramatic response to immunomodulatory treatments, suggest that symptoms arise from a combination of local, regional and systemic dysfunction. Ongoing research is directed at understanding the nature of the abnormal immune response, as well as identifying at-risk children, in order to provide for novel strategies of prevention and treatment. PMID:11466169

Leonard, H L; Swedo, S E

2001-06-01

25

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

26

Manipulation of behavioral disorders in autoimmune mice via prolactin.  

PubMed

Autoimmune mice perform poorly in two-way active avoidance tasks, and the extent of this performance deficit appears to be related to the extent of autoimmunity following developmental manipulations. In the current study, the pituitary hormone prolactin, which has immune-enhancing effects, was used to manipulate this behavioral disorder in adulthood. Prolatinergic manipulation may be achieved by the use of dopaminergic drugs. In two experiments, autoimmune NZB X NZW F1 (BW) mice received either pimozide (PIM; a D2 antagonist) or bromocriptine (CB154; a dopamine agonist) in their drinking water. Control subjects received plain water. Following treatment, subjects were tested in an activity monitor, and active avoidance learning. Circulating PRL levels, as measured by RIA, were significantly increased by PIM and significantly decreased by CB154. Neither drug affected circulating levels of autoantibodies to DNA or cardiolipin, a phospholipid. In Experiment 1, in which mice were tested at 12 weeks of age, after 6 weeks of drug treatment, PIM treated animals of both sexes showed significantly more failures to escape the shock in avoidance conditioning, while CB154 did not have significant effects. In Experiment 2, in which mice were tested at 16 weeks of age, after 12 weeks of drug treatment, CB154 treated females (males were not tested) showed significantly fewer failures to escape, while PIM did not have significant effects. The effects of PRL on behavior, and its relation to immune system function, are discussed. PMID:9333190

Waters, N S; Badura, L L; Ahmed, S A; Gogal, R M; Denenberg, V H

1997-11-01

27

Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism.  

PubMed

Autism is an age-dependent neurologic disorder that is often associated with autoimmune disorders in the patients' relatives. To evaluate the frequency of autoimmune disorders, as well as various prenatal and postnatal events in autism, we surveyed the families of 61 autistic patients and 46 healthy controls using questionnaires. The mean number of autoimmune disorders was greater in families with autism; 46% had two or more members with autoimmune disorders. As the number of family members with autoimmune disorders increased from one to three, the risk of autism was greater, with an odds ratio that increased from 1.9 to 5.5, respectively. In mothers and first-degree relatives of autistic children, there were more autoimmune disorders (16% and 21%) as compared to controls (2% and 4%), with odds ratios of 8.8 and 6.0, respectively. The most common autoimmune disorders in both groups were type 1 diabetes, adult rheumatoid arthritis, hypothyroidism, and systemic lupus erythematosus. Forty-six percent of the autism group reported having relatives with rheumatoid diseases, as compared to 26% of the controls. Prenatal maternal urinary tract, upper respiratory, and vaginal infections; asphyxia; prematurity, and seizures were more common in the autistic group, although the differences were not significant. Thirty-nine percent of the controls, but only 11% of the autistic, group, reported allergies. An increased number of autoimmune disorders suggests that in some families with autism, immune dysfunction could interact with various environmental factors to play a role in autism pathogenesis. PMID:10385847

Comi, A M; Zimmerman, A W; Frye, V H; Law, P A; Peeden, J N

1999-06-01

28

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

29

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

30

Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease  

Microsoft Academic Search

Background & Aims: The relationship between celiac disease and many autoimmune disorders has been explained by the sharing of a common genetic factor. In a multicenter national study, we examined the relationship between the prevalence of autoimmune disorders in celiac disease and the duration of exposure to gluten. Methods: Over a 6-month period, 909 patients with celiac disease (group A;

Alessandro Ventura; Giuseppe Magazzù; Luigi Greco

1999-01-01

31

Dual action of glatiramer acetate (Cop1) in the treatment of CNS autoimmune and neurodegenerative disorders  

Microsoft Academic Search

Protective autoimmunity is the body's defense mechanism against destructive self-compounds such as those commonly associated with neurodegenerative disorders. Autoimmune disease and neurodegenerative disorders can thus be viewed as two extreme manifestations of the same process. Therefore, when designing therapy, it is important to avoid an approach that will cure the one by invoking the other. One way to stop, or

Jonathan Kipnis; Michal Schwartz

2002-01-01

32

Auto-immune lymphoproliferative disorder and other secondary immune thrombocytopenias in childhood.  

PubMed

Primary immune thrombocytopenia (ITP) in childhood, typically presents as an acute self-limiting illness. However, secondary ITP is often a chronic disorder due to an underlying disease. Combined cytopenias in childhood, that is, secondary ITP occurring with auto-immune hemolytic anemia and/or auto-immune neutropenia, are often associated with disorders characterized by immune dysregulation. Such disorders include systemic lupus erythematosus, auto-immune lymphoproliferative syndrome, and common variable immune deficiency. Evans syndrome describes the combination of ITP, autoimmune hemolytic anemia, and/or autoimmune neutropenia. However, it is now clear that some patients with Evans syndrome have an underlying immunodeficiency. This report focuses on combined auto-immune cytopenias and highlights the challenges in their diagnosis and management. PMID:23109501

Price, Victoria

2013-01-01

33

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

34

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

35

Possible immunological disorders in autism: concomitant autoimmunity and immune tolerance.  

PubMed

Autism is a pervasive developmental disorder that affect children early in their life. Immunological disorders is one of several contributing factors that have been suggested to cause autism. Thirty autistic children aged 3-6 years and thirty non-autistic psychologically-free siblings were studied. Circulating IgA and IgG autoantibodies to casein and gluten dietary proteins were detected by enzyme-immunoassays (EIA). Circulating IgG antibodies to measles, mumps and rubella vaccine (M.M.R) and cytomeglovirus were investigated by EIA. Results revealed high seropositivity for autoantibodies to casein and gluten: 83.3% and 50% respectively in autistic children as compared to 10% and 6.7% positivity in the control group. Surprisingly, circulating anti-measles, anti-mumps and anti-rubella IgG were positive in only 50%, 73.3% and 53.3% respectively as compared to 100% positivity in the control group. Anti-CMV IgG was positive in 43.3% of the autistic children as compared to 7% in the control group. It is concluded that, autoimmune response to dietary proteins and deficient immune response to measles, mumps and rubella vaccine antigens might be associated with autism, as a leading cause or a resulting event. Further research is needed to confirm these findings. PMID:17974154

Kawashti, Maha I S; Amin, Omnia R; Rowehy, Nadia G

2006-01-01

36

Presence of systemic autoimmune disorders in patients with autoimmune thyroid diseases  

PubMed Central

Methods: 168 consecutive patients with ATD with positive antithyroid antibodies and 75 healthy subjects were tested for the presence of ANA. ANA positive patients were further evaluated by complete history, physical examination, blood and urine tests, and immunological studies. Patients with subjective xerophthalmia and xerostomia were examined by objective tests. Results: 58/168 (35%) patients with ATD were ANA positive compared with 7/75 (9%) healthy controls (p = 0.001). Of 58 ANA positive patients, 6 (10%) had anti-Ro antibodies, 1 had anti-Ro and anti-La antibodies, 7 (12%) had anti-dsDNA antibodies, and 7 (12%) had medium levels of IgG and/or IgM anticardiolipin antibodies (aCL). No healthy subjects had positive anti-dsDNA, antibodies against the extractable nuclear antigens, or aCL. 5/58 (9%) patients fulfilled the criteria for Sjögren's syndrome (SS). Two patients had features related to systemic lupus erythematosus. No healthy subjects had clinical or laboratory characteristics of systemic autoimmune disorders. Conclusion: ANA are detected in 1/3 of patients with ATD. Anti-dsDNA, anti-Ro, and aCL can also be found in ANA positive patients with ATD. SS occurs in about 1/10 of ANA positive patients with ATD. PMID:15308528

Tektonidou, M; Anapliotou, M; Vlachoyiannopoulo..., P; Moutsopoulos, H

2004-01-01

37

Intravenous immunoglobulin in autoimmune disorders: An insight into the immunoregulatory mechanisms  

Microsoft Academic Search

Intravenous immunoglobulin (IGIV) has increasingly been used for the treatment of autoimmune and systemic inflammatory diseases in addition to supportive therapy of immunodeficient patients. IGIV is beneficial in several diseases, including acute and chronic\\/relapsing diseases, autoimmune diseases and inflammatory disorders. Therapeutic efficacy of IGIV has also been established in a number of dermatologic diseases. Although a considerable progress has been

Jagadeesh Bayary; Sooryasarathi Dasgupta; Namita Misra; Amal Ephrem; Jean-Paul Duong Van Huyen; Sandrine Delignat; Gazzala Hassan; Giuseppina Caligiuri; Antonino Nicoletti; Sebastien Lacroix-Desmazes; Michel D. Kazatchkine; Srini Kaveri

2006-01-01

38

Hair disorders associated with autoimmune connective tissue diseases.  

PubMed

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

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

2014-10-01

39

HLA antigens in patients with interferon-?-induced autoimmune thyroid disorders in chronic hepatitis C  

Microsoft Academic Search

Background\\/Aims: To determine the immunological predisposition to autoimmune thyroid disorders induced by interferon-? therapy, human leukocyte antigen (HLA) was analyzed in patients with chronic hepatitis C who developed autoimmune thyroid disorders during or after treatment with interferon-?.Methods: Four hundred and thirty-nine patients with chronic hepatitis C (278 males and 161 females, aged 20–73 years) were treated with interferon-? (natural-?, 169;

Satoru Kakizaki; Hitoshi Takagi; Masami Murakami; Hisashi Takayama; Masatomo Mori

1999-01-01

40

Autoimmune enteropathy and colitis: is there a generalised autoimmune gut disorder?  

Microsoft Academic Search

Children with protracted diarrhoea, circulating enterocyte autoantibodies, and an enteropathy showing features of inappropriate HLA molecule expression on the jejunal crypt epithelium, often present with persistent blood and mucus in their stools. Eight children with autoimmune enteropathy were investigated for the presence of associated colonic disease. Six children with protracted diarrhoea, no circulating autoantibodies, and an enteropathy (in five of

S M Hill; P J Milla; G F Bottazzo; R Mirakian

1991-01-01

41

Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics  

Microsoft Academic Search

BackgroundA subgroup of children with obsessive-compulsive and tic disorders are proposed to have an infectious trigger. The purpose of this study was to investigate the relationship between group A streptococcal titers and symptom fluctuations in children with a clinical course resembling that described for pediatric autoimmune neuropsychiatric disorders associated with streptococcus.

Tanya K. Murphy; Muhammad Sajid; Ohel Soto; Nathan Shapira; Paula Edge; Mark Yang; Mark H. Lewis; Wayne K. Goodman

2004-01-01

42

Plasmacytoid dendritic cells and dermatological disorders : focus on their role in autoimmunity and tumors  

E-print Network

Title: Plasmacytoid dendritic cells and dermatological disorders : focus on their role in autoimmunity and tumors Short title : PDC and skin Charles Julie 1,2,3 , Chaperot Laurence 2,3 , Salameire conditions. Thereby, PDC have been observed in inflammatory immunoallergic dermatological disorders

Boyer, Edmond

43

Maternal History of Autoimmune Disease in Children Presenting with Tics and/or Obsessive-Compulsive Disorder  

PubMed Central

Objectives A commonality across a number of pediatric neuropsychiatric disorders is a higher than typical rate of familial – and especially maternal – autoimmune disease. Of recent interest, a subtype of obsessive-compulsive disorder (OCD) and tic disorders known collectively as Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is believed to be secondary to central nervous system (CNS) autoimmunity that occurs in relation to group A streptococcal infection. Thus, we hypothesized that a sample of children with OCD and/or tics would have an increased maternal risk for an autoimmune response relative to population norms. We also expected maternal prevalence of various autoimmune diseases to be higher among those participants that met the putative criteria for PANDAS. Methods We examined, via structured interview, the medical history of the biological mothers of 107 children with OCD and/or tics. Results Autoimmune disorders were reported in 17.8% of study mothers, which is significantly greater than the general prevalence among women in the United States (approximately 5%). Further, study mothers were more likely to report having an autoimmune disease if their children were considered “likely PANDAS” cases versus “unlikely PANDAS” cases. Conclusions Results offer preliminary support for hypothesized links between maternal autoimmune disease and both OCD/tics and PANDAS in youth. Further research is necessary to clarify these general associations; links to specific autoimmune disease; and relevance of autoimmune disease in other family members (e.g., fathers). PMID:20864184

Murphy, T.K.; Storch, E.A.; Turner, A.; Reid, J.M.; Tan, J.; Lewin, A.B.

2010-01-01

44

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

45

Biologics in children’s autoimmune disorders: efficacy and safety  

Microsoft Academic Search

Advances in understanding the pathogenesis of rheumatic diseases have led to the discovery of mechanisms of inflammation and\\u000a autoimmunity and have made possible the invention of new target-specific drugs. Biologic drugs, designed to inhibit specific\\u000a components of the immune system, such as cytokines, cytokine gene expression, and their complex interactions, have revolutionized\\u000a the treatment options in pediatric rheumatology. Only three

Luciana Breda; Marianna Del Torto; Sara De Sanctis; Francesco Chiarelli

2011-01-01

46

Left-Handedness, dyslexia, and autoimmune disorder: A critique  

Microsoft Academic Search

Concerns are raised regarding recent claims of an association between left-handedness and autoimmune disease and\\/or dyslexia. The available data provide only marginal support at best for these claims which, in addition, contain potentially misleading implications about left-handedness. Furthermore, some of the theoretical bases for the proposed associations are inconsistent with the relevant literature. Revisions in the theory are suggested to

Paul Satz; Henry V. Soper

1986-01-01

47

Questions and Answers on Autoimmunity and Autoimmune Diseases  

MedlinePLUS

... tissues. What are the types of autoimmunity? Particular autoimmune disorders are frequently classified into organ-specific disorders and ... dermatomyositis. What are some of the treatments for autoimmune diseases? Of first importance in treating any autoimmune disease ...

48

A Practical Approach to Treating Autoimmune Bullous Disorders with Systemic Medications  

PubMed Central

The bullous diseases comprise a heterogeneous group of skin disorders with distinct clinical and histological findings. They are characterized histologically by clefts at varying depths in the skin and are pathologically caused either by congenital defects or autoantibodies. Autoimmune bullous disorders are chronic conditions with significant morbidity and mortality in untreated patients. With the advent of immunosuppressive medications, mortality from these diseases has decreased significantly. However, complications from therapy itself are common causes of morbidity in these patients. Therefore, treatment of autoimmune bullous diseases is a challenge, as patients must remain on chronic medications with side effects that limit their use. This article aims to provide a practical approach to understanding the available medications for the treatment of autoimmune bullous diseases. PMID:20729961

Han, Anne

2009-01-01

49

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

50

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

PubMed

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

Nishioka, K; Sumida, T; Hasunuma, T

1996-08-01

51

Lymphoma development in patients with autoimmune and inflammatory disorders--what are the driving forces?  

PubMed

For decades, it has been known that patients with certain autoimmune and inflammatory disorders, such as rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS), have an increased risk of developing malignant lymphoma. Although the clinico-biological reasons for this association remain largely unknown, our knowledge has improved and new insights have been obtained. First, the direct link between autoimmunity and lymphomagenesis has been strengthened by large epidemiological studies showing a consistent risk increase of lymphoma associated with certain autoimmune/inflammatory conditions in independent cohorts from different countries. Second, a number of local and systemic disease-related risk factors in these diseases have been repeatedly linked to lymphoma development, with the prime examples being disease severity and the degree of inflammatory activity. Considering the key role of B- and T-cell activation in the pathogenesis of both autoimmunity and lymphoma, it is perhaps not surprising that longstanding chronic inflammation and/or antigen stimulation have emerged as major predisposing factors of lymphoma in patients with active autoimmune disease. Finally, increasing evidence suggests that lymphomas associated with autoimmunity constitute a different spectrum of entities compared to lymphomas arising in patients without any known autoimmune or inflammatory conditions, pointing to a different pathobiology. In this review, we summarize the recent literature that supports a direct or indirect link between immune-mediated disease and lymphoma and describe the characteristics of lymphomas developing in the different diseases. We also discuss molecular, genetic and microenvironmental factors that may come into play in the pathobiology of these disorders. PMID:24333759

Baecklund, Eva; Smedby, Karin E; Sutton, Lesley-Ann; Askling, Johan; Rosenquist, Richard

2014-02-01

52

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

PubMed Central

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

Kurlan, Roger; Leckman, James

2010-01-01

53

Incidence and Significance of Organ-Specific Autoimmune Disorders (Clinical, Latent or only Autoantibodies) in Patients with Vitiligo  

Microsoft Academic Search

The frequency of autoimmune disorders was determined in 373 vitiligo patients and in controls matched for sex, age and race. Vitiligo patients had an increased frequency of clinical autoimmune diseases of thyroid (7.5%), stomach (0.8%), parathyroid (1%), adrenal gland (1.3%). Vitiligo patients, without clinical signs of overt autoimmune diseases, also had a statistically significant increase in the frequency of gastric

C. Betterle; A. Caretto; A. De Zio; B. Pedini; C. Veller-Fornasa; A. Cecchetto; F. Accordi; A. Peserico

1985-01-01

54

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

Microsoft Academic Search

BACKGROUND AND AIMSDuration of gluten exposure seems to predispose adolescents with coeliac disease to autoimmune diseases. In a retrospective cohort study, we assessed the relationship between autoimmune disorders and actual gluten exposure in patients in whom coeliac disease was diagnosed in adult life (?16 years).METHODSWe screened for the presence of autoimmunity in 605 controls (16–84 years) and 422 patients (16–84

C Sategna Guidetti; E Solerio; N Scaglione; G Aimo; G Mengozzi

2001-01-01

55

Audit to assess the prevalence of autoimmune disorders among patients suffering from psychiatric illnesses.  

PubMed

While knowledge of the aetiology of psychiatric disorders is complex and has not been fully elucidated, recently it has been noted that a sizeable proportion of psychiatric patients have coexisting immunological health conditions. It is debatable whether inflammatory factors plays a role in the aetiology of the psychiatric conditions, or if psychiatric conditions predispose to immune dysfunction. However, previous work has given weight to the theory that the immune system has important neuromodulatory roles in the brain, and disturbances in this system can lead to psychiatric manifestations. Epidemiological evidence is needed to explore the strength of the correlation between immune conditions and psychiatric disorders, and this audit attempts to investigate this potential association using the psychiatric patient databaseof Bedford East Community Mental Health Team (Bedfordshire, UK). In this audit, the patient information was analysed to obtain prevalence data for an array of autoimmune conditions. This was then compared to the expected prevalence of the same autoimmune conditions. The results showed that patients with each psychiatric condition had a higher than expected prevalence of autoimmune conditions overall. The most striking discrepancy was that the percentage of patients with coexisting hypothyroidism was higher than expected in almost every psychiatric condition recorded. Other patterns in prevalence of autoimmune conditions were also noted. A causative link between psychiatric and autoimmune diseases is still questionable, and this issue needs to be researched further in terms of prevalence data and aetiological evidence. There are significant implications for clinical practice if a greater incidence of autoimmune conditions among psychiatric patients is proven. This includes screening opportunities and risk assessments, as well as potential for new pharmacological therapies based around immune regulation. PMID:23995199

Vaja, Rakhee; Agius, Mark; Zaman, Rashid

2013-09-01

56

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

57

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

PubMed Central

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

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

2009-01-01

58

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

Microsoft Academic Search

Some autoimmune disorders are increas- ingly recognized as risk factors for non- Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self- reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence

Karin Ekstrom Smedby; Claire M. Vajdic; Michael Falster; Eric A. Engels; Otoniel Martõ ´ nez-Maza; Jennifer Turner; Henrik Hjalgrim; Paolo Vineis; Adele Seniori Costantini; Paige M. Bracci; Elizabeth A. Holly; John J. Spinelli; Tongzhang Zheng; Brian C.-H. Chiu; Marc Maynadie; Paul Brennan; Scott Davis; James R. Cerhan; Elizabeth C. Breen; Andrew E. Grulich; Wendy Cozen

2008-01-01

59

Diminished regulatory T cells in cutaneous lesions of thymoma-associated multi-organ autoimmunity: a newly described paraneoplastic autoimmune disorder with fatal clinical course  

PubMed Central

Thymoma-associated multi-organ autoimmunity is a rare, autoimmune disease that causes colitis, liver dysfunction and cutaneous graft-versus-host (GVH)-like skin damage. This paraneoplastic autoimmune disorder may be due to inadequate T cell selection in the tumour environment of the thymus. Although sporadic case reports have revealed its clinical features, little is known about its pathological mechanism. By comparing the skin-infiltrating T cell subsets with those of GVH disease (GVHD) and other inflammatory skin diseases, we sought to elucidate the pathological mechanism of thymoma-associated multi-organ autoimmunity. Histopathological and immunohistochemical analysis of skin biopsies was performed for three patients with thymoma-associated multi-organ autoimmunity. Histopathological findings of thymoma-associated multi-organ autoimmunity were indistinguishable from those of patients with acute GVHD, although the aetiologies of these diseases are completely different. The frequency of regulatory T cells (Tregs) is reduced in cutaneous lesions and CD8+ cytotoxic T lymphocytes that massively infiltrate into the epidermis of patients with thymoma-associated multi-organ autoimmunity. Additionally, the ratio of T helper type 17 (Th17) cells to CD4+ cells in patients with thymoma-associated multi-organ autoimmunity and acute GVHD was higher than that in healthy controls, but similar to that in psoriasis vulgaris patients. Similarity of the skin-infiltrating T cell subsets with those of acute GVHD suggested that skin damage in patients with thymoma-associated multi-organ autoimmunity might be induced by self-reactive cytotoxic T lymphocytes under the diminished suppressive capacity of Tregs. PMID:21985362

Hanafusa, T; Azukizawa, H; Kitaba, S; Murota, H; Umegaki, N; Terao, M; Sano, S; Nakagiri, T; Okumura, M; Katayama, I

2011-01-01

60

Undiagnosed coeliac disease and risk of autoimmune disorders in subjects with Type I diabetes mellitus  

Microsoft Academic Search

Aims\\/hypothesis. We tested the hypothesis that silent coeliac disease is more frequent than expected in both patients with Type I (insulin-dependent)\\u000a diabetes mellitus and their first-degree relatives. We evaluated how the presence of other autoimmune disorders in diabetic\\u000a patients and their first-degree relatives is related to silent, unrecognized coeliac disease. Methods. Sera from 491 subjects with Type I diabetes, 824

A. Tommasini; G. Tonini; E. Buratti; M. Pocecco; C. Tortul; M. Valussi; G. Crichiutti; I. Berti; C. Trevisiol; E. Azzoni; E. Neri; G. Torre; S. Martelossi; M. Soban; A. Lenhardt; L. Cattin; A. Ventura

2001-01-01

61

Animal models for autoimmune demyelinating disorders of the nervous system  

Microsoft Academic Search

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that takes a relapsing–remitting or a progressive course (reviewed in Refs 1,2). Its counterpart in the peripheral nervous system (PNS) is chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) (reviewed in Ref. 3). In addition, there are acute, monophasic disorders, such as the inflammatory demyelinating polyradiculoneuropathy termed Guillain–Barré syndrome

Ralf Gold; Hans-Peter Hartung; Klaus V Toyka

2000-01-01

62

Associated Autoimmune Diseases  

MedlinePLUS

... individuals with autoimmune diseases are women. In an autoimmune disorder, the cells of the immune system produce antibodies ... damage. This is not a complete listing of autoimmune diseases associated with celiac disease. Anyone who has unexplained, ...

63

Antibodies and neuronal autoimmune disorders of the CNS.  

PubMed

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

Graus, Francesc; Saiz, Albert; Dalmau, Josep

2010-04-01

64

Olfaction, psychiatric disorders and autoimmunity: is there a common genetic association?  

PubMed

Psychiatric diseases are often associated with mild alterations in immune functions (e.g., schizophrenia) as well as autoimmune features. Recent evidence suggests that autoimmune diseases (AD) demonstrate a higher prevalence of psychiatric disorders, such as depression and psychosis, than in the normal population. Patients with AD often have an olfactory impairment as well, based on smell studies, accompanied by olfactory regional alterations in neuroimaging. Some evidence suggests that olfactory gene receptors have additional functions in the brain, related to their direct anatomical connection to the limbic system. For example, odor sensing may explain HLA-dissimilar mate selection in humans and animals. Recently, a large cluster of the olfactory receptor (OR) genes was mapped in proximity to the HLA locus on chromosome 6. The HLA and linked OR genes are clustered in haplotypes and are highly polymorphic. This finding may constitute an association among autoimmunity, psychiatric disorders and smell impairment. In this review, we examine the anatomic, genetic and clinical clues that may support an association among these conditions. PMID:19127459

Ortega-Hernandez, Oscar-Danilo; Kivity, Shaye; Shoenfeld, Yehuda

2009-01-01

65

Prospective Identification and Treatment of Children With Pediatric Autoimmune Neuropsychiatric Disorder Associated With Group A Streptococcal Infection (PANDAS)  

Microsoft Academic Search

Background: The current diagnostic criteria for pedi- atric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS) are pe- diatric onset, neuropsychiatric disorder (obsessive- compulsive disorder (OCD)) and\\/or tic disorder; abrupt onset and\\/or episodic course of symptoms; association with group A-hemolytic streptococcal (GABHS) infec- tion; and association with neurological abnormalities (mo- toric hyperactivity or adventitious movements, includ- ing choreiform

Marie Lynd Murphy; Michael E. Pichichero

2002-01-01

66

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

67

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

ERIC Educational Resources Information Center

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

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

2006-01-01

68

Understanding Autoimmune Diseases  

MedlinePLUS

... the understanding of the genetics and causes of autoimmune disorders and result in improvements in diagnosing and treating ... privately supported clinical trials for a variety of autoimmune disorders, visit www.clinicaltrials.gov . Key Words Acquired immune ...

69

Interleukin-2 and the septohippocampal system: intrinsic actions and autoimmune processes relevant to neuropsychiatric disorders.  

PubMed

The effects of IL-2 on brain development, function, and disease are the result of IL-2's actions in the peripheral immune system and its intrinsic actions in the central nervous system (CNS). Determining whether, and under what circumstances (e.g., development, acute injury), these different actions of IL-2 are operative in the brain is essential to make significant advances in understanding the multifaceted affects of IL-2 on CNS function and disease, including psychiatric disorders. For several decades, there has been a great deal of speculation about the role of autoimmunity in brain disease. More recently, we have learned a great deal about the role of cytokines on neurobiological processes, and there have been many studies that have found peripheral immune alterations in patients with neurological and neuropsychiatric diseases. Despite a plethora of published literature, almost all of this data in humans is correlative and much of the basic research has understandably relied on simpler models (e.g., in vitro models). Good animal models such as our IL-2 knockout mouse model could provide valuable new insight into understanding how the complex biology of a cytokine such as IL-2 can have simultaneous, dynamic effects on multiple systems (e.g., regulating homeostasis in the brain and immune system, autoimmunity that can affect both systems). Animal models can also provide much needed new data elucidating neuroimmunological and autoimmune processes involved in brain development and disease. Such information may ultimately provide critical new insight into the role of brain cytokines and autoimmunity in prominent neurological and neuropsychiatric diseases (e.g., Alzheimer's disease, autism, multiple sclerosis, schizophrenia). PMID:22231830

Petitto, John M; Huang, Zhi; Meola, Danielle; Ha, Grace K; Dauer, Daniel

2012-01-01

70

Parvovirus B19 infection of brain: possible role of gender in determining mental illness and autoimmune thyroid disorders.  

PubMed

Major theories about the etiologies of chronic mental illnesses such as bipolar disorder and schizophrenia include genetic and environmental factors such as famine and infection. It is likely that multiple genes play a role in the pathogenesis of these disorders, but no single gene has been identified as causative. Several viruses have been investigated as potential candidates, but conflicting reports exist. Although a relationship between bipolar disorder and schizophrenia with autoimmune disorders has also been documented for many years, reports are often conflicting. We hypothesize that parvovirus B19 (B19), a common human pathogen, due to its ability to infect the brain and induce autoimmunity, is a strong candidate that may unite prevailing theories. In particular, our preliminary data suggest that B19 may be most likely involved in co-morbid bipolar and autoimmune thyroid disorders in females. In schizophrenics, the gender trend may be reversed. We propose that there is a complex interaction between immuno-genetics, autoimmunity, gender, and B19 infection that leads to at least some forms of bipolar disorder and schizophrenia. Future studies that investigate this hypothesis are warranted and outlined. PMID:17196758

Hammond, C J; Hobbs, J A

2007-01-01

71

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

72

NEWS AND COMMENTARY Autoimmunity  

E-print Network

-cell-depen- dent autoimmune diabetes. NOD mice are also prone to multiple other autoimmune disorders, spontaneouslyNEWS AND COMMENTARY Autoimmunity Beyond the immune system Adrian Liston Immunology and Cell Biology the susceptibility of an individual to autoimmune disease. In this study, Lonyai et al. use the non- obese diabetic

Cai, Long

73

A review of the current literature and a guide to the early diagnosis of autoimmune disorders associated with neuromyelitis optica.  

PubMed

Neuromyelitis optica (NMO) is an immune-mediated neurological disorder characterised by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis. A serum biomarker, aquaporin-4 IgG, the autoantibody against aquaporin-4 water channel, has been specifically associated with NMO and has assisted early recognition and prediction of relapses. Less commonly, a monophasic course, associated with antibodies to myelin oligodendrocyte glycoprotein has been reported. Specific diagnostic criteria have been defined; however, some cases that do not fulfil these criteria (but are nevertheless associated with aquaporin-4 IgG) are classified as NMO spectrum disorder and follow the same relapsing course. An ever-growing list of autoimmune disorders, both organ-specific and non-organ-specific, have been associated in up to 20-30% of patients with NMO. These disorders, which may become symptomatic before or after the development of NMO, are often diagnosed long after the diagnosis of NMO, as symptoms may be wrongly attributed to NMO, its residual effects or medication side effects. In addition, autoantibodies can be found in patients with NMO without coexisting disease (up to 40% in some series) and maybe suggestive of a heightened humoral immune response. We present a comprehensive review of the current literature on autoimmune disorders co-existing with NMO and identified 22 autoimmune conditions (myasthenia gravis, coeliac disease, ulcerative colitis, sclerosing cholangitis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid antibody syndrome, Sjogren's syndrome, autoimmune hypothyroidism, immune thrombocytopenic purpura, pernicious anaemia, narcolepsy, pemphigus foliaceus, alopecia areata, psoriasis, scleroderma, dermatitis herpetiformis, polymyositis, chronic inflammatory demyelinating polyneuropathy, paraneoplastic disorders, insulin dependent diabetes mellitus and autoimmune encephalitis). PMID:24512514

Iyer, Anand; Elsone, Liene; Appleton, Richard; Jacob, Anu

2014-05-01

74

Autoimmune Inner Ear Disease (AIED)  

MedlinePLUS

... debris in the ear can cause problems. Some autoimmune disorders that can affect the ear include Cogan’s syndrome, ... even indistinguishable, from other vestibular disorders. Diagnosing an autoimmune disorder as the cause of inner ear symptoms can ...

75

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

Microsoft Academic Search

OBJECTIVETo 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.METHODSThe clinical history of the four patients is reported with details concerning age, sex, indication for IVIG treatment, risk factors, timing of the MI

Ori Elkayam; Daphna Paran; Ronny Milo; Yaron Davidovitz; Dorit Almoznino-Sarafian; David Zeltser; Michael Yaron; Dan Caspi

2000-01-01

76

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

PubMed

Accurate recognition of movement disorder phenomenology may differentiate children with anti-N-methyl D-aspartate receptor (NMDAR) encephalitis, autoimmune basal ganglia encephalitis (BGE), and Sydenham's chorea (SC). Three neurologists blinded to the diagnoses recorded dominant and associated movement disorders seen on videos of 31 patients with anti-NMDAR encephalitis (n?=?10), BGE (n?=?12), and SC (n?=?9). Stereotypy was only seen in anti-NMDAR encephalitis (8/10) and not in BGE and SC (P?Disorder Society. PMID:25154478

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

2014-10-01

77

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) and IPEX-Related Disorders: an Evolving Web of Heritable Autoimmune Diseases  

PubMed Central

Purpose of review To summarize recent progress in our understanding of Immune Dysregulation, Polyendocrinopathy, enteropathy, X-linked (IPEX) and IPEX-related disorders. Recent findings A number of Mendelian disorders of immune dysregulation and autoimmunity have been noted to result from defects in T regulatory (TR) cell development and function. The best characterized of these is Immune Dysregulation, Polyendocrinopathy, enteropathy, X-linked (IPEX), resulting from mutations affecting FOXP3. A number of other gene defects that affect TR cell function also give rise to IPEX-related phenotypes, including loss of function mutations in CD25 and STAT5b and ITCH. Recent progress includes the identification of gain of function mutations in STAT1 as a cause of an IPEX-like disease, emerging FOXP3 genotype/phenotype relationships in IPEX, and the elucidation of a role for the microbiota in the immune dysregulation associated with regulatory T cell deficiency. Summary An expanding spectrum of genetic defects that compromise TR cell function underlies human disorders of immune dysregulation and autoimmunity. Collectively, these disorders offer novel insights into pathways of peripheral tolerance and their disruption in autoimmunity. PMID:24240290

Verbsky, James W.; Chatila, Talal A.

2014-01-01

78

Genetics Home Reference: Autoimmune Addison disease  

MedlinePLUS

... of each kidney. It is classified as an autoimmune disorder because it results from a malfunctioning immune system ... disease or their family members often have another autoimmune disorder, most commonly autoimmune thyroid disease or type 1 ...

79

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

PubMed Central

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

Macerollo, Antonella; Martino, Davide

2013-01-01

80

Analysis of the Expression of Fas, FasL and Bcl2 in the Pathogenesis of Autoimmune Thyroid Disorders  

Microsoft Academic Search

To investigate the expression of apoptosis-related protein (Fas, FasL, and Bcl-2) in the pathogenesis of autoimmune thyroid disorders (ATDs), immunohistochemical staining was performed on 20 Hashimoto's thyroiditis (HT), 20 Graves' disease (GD), and 20 thyroid follicular adenoma (TFA, as control). All the cases expressed Fas, mainly on the cell surface and cytoplasm. FasL was found in 17 cases of the

Shenren Chen; S. M. Fazle Akbar; Zhichao Zhen; Yiping Luo; Lijuan Deng; Haihua Huang; Linxin Chen; Wei Li

2004-01-01

81

A review of high-dose intravenous immunoglobulin (hdIVIg) in the treatment of the autoimmune blistering disorders  

Microsoft Academic Search

Summary High-dose intravenous immunoglobulin (hdIVIg) is being used increasingly for dermatological indications. Its mode of action is via a number of proposed mechanisms and it is not associated with the many side-effects of steroids and other immunosuppressive agents. The evidence for using hdIVIg in the treatment of autoimmune bullous disorders is based on uncontrolled trials and case reports. However, there

S. Jolles

2001-01-01

82

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; Araujo, Marcelo Grossi; Campi-Azevedo, Ana Carolina; Teixeira-Carvalho, Andrea; Peruhype-Magalhaes, Vanessa; Trindade, Bruno Caetano; dos Santos Dias, Raquel; Martins, Marina Lobato; Carneiro-Proietti, Anna Barbara de Freitas; Guedes, Antonio Carlos; Goncalves, Denise Utsch; Martins-Filho, Olindo Assis

2013-01-01

83

Plasmacytoid dendritic cells and dermatological disorders: focus on their role in autoimmunity and cancer  

PubMed Central

Dendritic cells (DC), considered as immunological sentinels of the organism since they are antigen presenting cells, create the link between innate and adaptive immunity. DC include myeloid dendritic cells (MDC) and plasmacytoid dendritic cells (PDC). The presence of PDC, cells capable of producing large quantities of interferon alpha (IFN-?) in response to pathogenic agents or danger signals, seem to be tightly related to pathological conditions. Thereby, PDC have been observed in inflammatory immunoallergic dermatological disorders, in malignant cutaneous tumours and in cutaneous lesions of infectious origin. They seem to play a crucial role in the initiation of the pathological process of autoimmune diseases such as lupus or psoriasis. Their function within a tumour context is not as well known and is controversial. They could have a tolerogenic role towards tumour cells in the absence of activator but they also have the capacity to become activated in response to Toll-like receptor (TLR) ligands and could therefore be usefull for therapeutic purposes. PMID:19850548

Charles, Julie; Chaperot, Laurence; Salameire, Dimitri; Di Domizio, Jeremy; Aspord, Caroline; Gressin, Remy; Jacob, Marie-Christine; Richard, Marie-Jeanne; Beani, Jean-Claude; Plumas, Joel; Leccia, Marie-Therese

2010-01-01

84

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

PubMed Central

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

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

2014-01-01

85

Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection  

Microsoft Academic Search

Streptococcal infections can induce obsessive-compulsive and tic disorders. In children, this syndrome, frequently associated with disturbances in attention, learning and mood, has been designated pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Autoantibodies recognizing central nervous system (CNS) epitopes are found in sera of most PANDAS subjects, but may not be unique to this neuropsychiatric subset. In support of

K Yaddanapudi; M Hornig; R Serge; J De Miranda; A Baghban; G Villar; W I Lipkin

2010-01-01

86

Immunoregulatory disorders associated with hereditary angioedema. I. Clinical manifestations of autoimmune disease.  

PubMed

Occasional reports have appeared linking hereditary angioedema (HAE) with autoimmune diseases. We have systematically evaluated 157 patients for manifestations of autoimmunity. Nineteen of these patients (12%) had clinical immunoregulatory diseases including glomerulonephritis (five patients), Sjögren's syndrome (three), inflammatory bowel disease (three), thyroiditis (two), systemic lupus erythematosus (one), drug-induced lupus (one), rheumatoid arthritis (one), juvenile rheumatoid arthritis with IgA deficiency (one), incipient pernicious anemia (one), and sicca syndrome (one). All eight patients with HAE who developed an autoimmune disease with a known human histocompatibility antigen association developed a disease associated with their histocompatibility antigen haplotype (p = 0.014). Although only four patients developed Sjögren's syndrome or sicca syndrome, an additional nine manifested part of the sicca complex. We also found patients with HAE with features suggestive of an immune-based abnormality. These features included idiopathic pancreatitis (three patients), Raynaud's disease (two), partial lipodystrophy (one), chronic chorioretinitis (one), and alopecia universalis (one). PMID:3084606

Brickman, C M; Tsokos, G C; Balow, J E; Lawley, T J; Santaella, M; Hammer, C H; Frank, M M

1986-05-01

87

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

PubMed Central

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

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

2013-01-01

88

Induction of Autoimmunity Through Bystander Effects. Lessons from Immunological Disorders Induced by Heavy Metals  

Microsoft Academic Search

Autoreactive T cells exist in healthy individuals and represent a potential reservoir of pathogenic effectors which, when stimulated by microbial adjuvants, could trigger an autoimmune disease. Experimental studies have indicated that xenobiotics, well defined from a chemical point of view, could promote the differentiation of autoreactive T cells towards a pathogenic pathway. It is therefore theoretically possible that compounds present

Gilbert J. Fournie; Magali Mas; Bastien Cautain; Magali Savignac; Jean-François Subra; Lucette Pelletier; Abdelhadi Saoudi; Dominique Lagrange; Maryline Calise; Philippe Druet

2001-01-01

89

Vasoactive intestinal peptide induces regulatory dendritic cells with therapeutic effects on autoimmune disorders  

Microsoft Academic Search

The induction of antigen-specific tolerance is critical for the prevention of autoimmunity and maintenance of immune tolerance. In addition to their classical role as sentinels of the immune response-inducing T cell reactivity, dendritic cells (DCs) play an important role in maintaining peripheral tolerance through the induction\\/activation of regulatory T cells (Tr). The possibility to generate tolerogenic DCs opens new therapeutic

Alejo Chorny; Elena Gonzalez-Rey; Amelia Fernandez-Martin; David Pozo; Doina Ganea; Mario Delgado

2005-01-01

90

Autoimmunity and reproduction  

Microsoft Academic Search

Objective: To review the association between autoimmunity and reproductive failure.Design: A MEDLINE search done from 1965 to 1996. More than 300 original and review articles were evaluated, from which the most relevant were selected.Result(s): Autoimmune processes now are accepted widely as one of the possible mechanisms of many human diseases. The presence of autoimmune disorders has been associated repeatedly with

Eli Geva; Ami Amit; Liat Lerner-Geva; Joseph B. Lessing

1997-01-01

91

Autoimmune paediatric liver disease  

Microsoft Academic Search

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and\\/or antinuclear antibody (SMA\\/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients

Giorgina Mieli-Vergani; Diego Vergani

2008-01-01

92

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

93

Shaking Out Clues to Autoimmune Disease  

MedlinePLUS

... into how an immune cell involved in several autoimmune disorders is regulated. Among their findings was a potential ... but they’ve also been linked with several autoimmune disorders. Th17 cells, along with other types of helper ...

94

Introduction to immunology and autoimmunity.  

PubMed

Autoimmune disease occurs when the immune system attacks self-molecules as a result of a breakdown of immunologic tolerance to autoreactive immune cells. Many autoimmune disorders have been strongly associated with genetic, infectious, and/or environmental predisposing factors. Comprising multiple disorders and symptoms ranging from organ-specific to systemic, autoimmune diseases include insulin-dependent diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, thyroiditis, and multiple sclerosis. There are also implications of autoimmune pathology in such common health problems as arteriosclerosis, inflammatory bowel disease, schizophrenia, and certain types of infertility. Largely of unknown etiology, autoimmune disorders affect approximately 3% of the North American and European populations, > 75% of those affected being women. This discussion provides a brief introduction to the immune system and tolerance maintenance, an overview of selected autoimmune diseases and possible mechanisms of immune autoreactivity, and a review of experimental autoimmune models. PMID:10502528

Smith, D A; Germolec, D R

1999-10-01

95

The Stiff-Person Syndrome: An Autoimmune Disorder Affecting Neurotransmission of g-Aminobutyric Acid  

Microsoft Academic Search

The stiff-person syndrome, a rare and disabling disorder, is characterized by muscle rigidity and episodic spasms that involve axial and limb musculature. Continuous contrac- tion of agonist and antagonist muscles caused by involun- tary motor-unit firing at rest are the hallmark clinical and electrophysiologic signs of the disease. Except for global muscle stiffness, results of neurologic examination are usu- ally

Lucien M. Levy; Marinos C. Dalakas; Mary Kay Floeter

1999-01-01

96

There is no evidence of an inverse relationship between T H2-mediated atopy and T H1-mediated autoimmune disorders: Lack of support for the hygiene hypothesis  

Microsoft Academic Search

Background: The findings of an inverse relationship between TH1- and TH2-mediated disorders would provide strong empiric support to the hygiene hypothesis. Objective: We sought to investigate the relationship between TH2-mediated atopic allergy and TH1-mediated autoimmune conditions in a nationally representative population. Methods: We used logistic regression to analyze adult data from the Third National Health and Nutrition Examination Survey. Data

Aziz Sheikh; Liam Smeeth; Richard Hubbard

2003-01-01

97

Familial characteristics of autoimmune and hematologic disorders in 8,406 multiple myeloma patients: A population-based case-control study  

Microsoft Academic Search

A population-based case-control study was conducted to evaluate risk of developing multiple myeloma (MM) associated with per- sonal history of autoimmune diseases and occurrence of autoim- mune and selected hematologic disorders in first-degree relatives. Data were obtained for all (n 5 8,406) MM cases diagnosed in Sweden (1958-1998), with linkable relatives, 16,543 matched con- trols and first-degree relatives of cases

Ola Landgren; Martha S. Linet; Mary L. McMaster; Gloria Gridley; Kari Hemminki; Lynn R. Goldin

2006-01-01

98

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

99

Autoimmune hepatitis  

MedlinePLUS

Autoimmune hepatitis is inflammation of the liver that occurs when immune cells mistake the liver's normal cells for ... lupus erythematosus Thyroiditis Type 1 diabetes Ulcerative colitis ... sometimes occurs in relatives of people with autoimmune ...

100

Autoimmune Keratitis  

Microsoft Academic Search

Autoimmune keratitis can present with a number of clinical profiles and with a number of underlying autoimmune systemic diseases.\\u000a Autoimmune keratitis should be suspected in all cases of unexplained stromal ulceration and should be closely monitored for\\u000a rate of progression if autoimmune keratitis is identified. Rapidly progressive ulcerative disease needs prompt and appropriate\\u000a immunosuppression.\\u000a \\u000a Most patients with collagen vascular stromal

John D. Gottsch

101

Bone Marrow or Blood Stem Cell Transplants in Children With Severe Forms of Autoimmune Disorders or Certain Types of ...  

MedlinePLUS

... Sept. 25, 2013 Bone Marrow or Blood Stem Cell Transplants in Children With Severe Forms of Autoimmune ... HSCT may help your child. Understanding Hematopoietic Stem Cell Transplants What are hematopoietic stem cells? Hematopoietic stem ...

102

Hepatitis C virus and autoimmunity  

Microsoft Academic Search

Hepatitis C virus infection is associated with several extrahepatic manifestations. About 60% of patients infected with HCV\\u000a develop at least one extrahepatic manifestation. The majority of these diseases seem to be triggered through autoimmune mechanisms,\\u000a such as autoantibody production, autoreactive T cells and complex autoimmune mechanisms leading to systemic autoimmune disorders.\\u000a In this review we categorize these diseases into three

Barbara C. Böckle; Norbert T. Sepp

2010-01-01

103

Autoimmunity in psychiatry.  

PubMed

Current knowledge of the role of autoimmunity in the pathogenesis of the main psychiatric disorders is briefly outlined. The significance of immunological effects on synaptic transmission and associated neuropsychiatric syndromes is emphasised. Clinical psychiatrists are encouraged to keep abreast of developments in this increasingly important area. PMID:22550326

Davison, Kenneth

2012-05-01

104

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

PubMed Central

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

Zhu, Conghui; Xie, Qunhui; Zhao, Bin

2014-01-01

105

Leflunomide (HWA 486), a novel immunomodulating compound for the treatment of autoimmune disorders and reactions leading to transplantation rejection  

Microsoft Academic Search

Leflunomide has been shown to be very effective in preventing and curing several autoimmune animal diseases. Further, this agent is as effective as cyclosporin A in preventing the rejection of skin and kidney transplants in rats. Preliminary results from patients suffering from severe cases of rheumatoid arthritis demonstrated that clinical and immunological parameters could be improved with leflunomide therapy. Mode

R. R. Bartlett; M. Dimitrijevic; T. Mattar; T. Zielinski; T. Germann; E. Rüde; G. H. Thoenes; C. C. A. Küchle; H.-U. Schorlemmer; E. Bremer; A. Finnegan; R. Schleyerbach

1991-01-01

106

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

107

Functional Energetics of CD4+Cellular Immunity in Monoclonal Antibody-Associated Progressive Multifocal Leukoencephalopathy in Autoimmune Disorders  

Microsoft Academic Search

BackgroundProgressive multifocal leukoencephalopathy (PML) is an opportunistic central nervous system- (CNS-) infection that typically occurs in a subset of immunocompromised individuals. An increasing incidence of PML has recently been reported in patients receiving monoclonal antibody (mAb) therapy for the treatment of autoimmune diseases, particularly those treated with natalizumab, efalizumab and rituximab. Intracellular CD4+-ATP-concentration (iATP) functionally reflects cellular immunocompetence and inversely

Aiden Haghikia; Moritz Perrech; Bartosz Pula; Sabrina Ruhrmann; Anja Potthoff; Norbert H. Brockmeyer; Susan Goelz; Heinz Wiendl; Hans Lindå; Tjalf Ziemssen; Sergio E. Baranzini; Tor-Björn Käll; Dietmar Bengel; Tomas Olsson; Ralf Gold; Andrew Chan; Mehrdad Matloubian

2011-01-01

108

Differential Mucosal IL17 Expression in Two Gliadin-Induced Disorders: Gluten Sensitivity and the Autoimmune Enteropathy Celiac Disease  

Microsoft Academic Search

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

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

2010-01-01

109

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

110

Celiac Disease-Associated Autoimmune Endocrinopathies  

Microsoft Academic Search

Celiac disease (CD) is an autoimmune disorder induced by gluten intake in genetically susceptible individ- uals. It is characterized by the presence of serum antibodies to endomysium, reticulin, gliadin, and tissue transglutaminase. The incidence of CD in various autoimmune disorders is increased 10- to 30-fold in comparison to the general population, although in many cases CD is clinically asymptomatic or

Vijay Kumar; Manoj Rajadhyaksha; Jacobo Wortsman

2001-01-01

111

Common variable immune deficiency and autoimmunity  

Microsoft Academic Search

Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by various degrees of hypogammaglobulinemia. Similar to many immunodeficiency disorders, autoimmunity is common with an association with autoimmune cytopenias, a sarcoidosis-like disorder and inflammatory bowel disease. Recent efforts have characterized selective immunological defects and genetic associations in CVID and demonstrate an increased tendency towards loss of tolerance. The mainstay of treatment

Daniel Brandt; M. Eric Gershwin

2006-01-01

112

Immunologic derangement preceding clinical autoimmunity.  

PubMed

Autoantibodies are valuable markers for the recognition of autoimmune diseases. Over the last 25 years, several investigators have consistently shown that autoantibodies precede the clinical onset of cognate diseases by years or decades. This phenomenon, regularly observed in the natural history of autoimmune diseases, indicates that autoimmunity develops through successive stages across a variable period of time until the characteristic manifestations of disease are clinically apparent. Recent evidence indicates that the pre-clinical stages of autoimmune diseases involve a series of immunologic derangements and that this process is dynamic and progressive. During the years preceding clinical disease onset, there is progressive intensification in the humoral autoimmune response, characterized by increases in autoantibody titer, avidity, number of immunoglobulin isotypes, and spread of epitopes and of autoantigens targeted. This scenario is reminiscent of cancer processes that develop slowly by means of progressive stages, and may be interrupted by early detection and therapeutic intervention. Therefore, it might be reasoned that early intervention may be more effective in reverting the less firmly established autoimmune abnormalities at the pre-clinical stage of autoimmunity. With the continuous progress in novel immunologic therapeutic strategies, one can envision the possibility that early intervention at pre-clinical stages may lead to prevention of overt disease development and even cure of the autoimmune disorder. PMID:25228734

Dellavance, A; Coelho Andrade, L E

2014-10-01

113

Genetics Home Reference: Autoimmune polyglandular syndrome, type 1  

MedlinePLUS

... the body's organs. It is one of many autoimmune diseases, which are disorders that occur when the immune ... Health National Institute of Allergy and Infectious Diseases: Autoimmune Diseases Educational resources - Information pages (3 links) Patient support - ...

114

Associated Autoimmunity in Addison's Disease  

Microsoft Academic Search

As the last extensive series of patients with Addison's disease and coincident autoimmune phenomena were published approximately two decades ago, we studied the cause of the disease, the prevalence of autoimmune disorders and the frequency of occurrence of autoantibodies in 91 patients (31 men and 60 women, mean age 45.3-years-old, range 12–77) with Addison's disease.The cause of Addison's disease in

Pierre M. J. Zelissen; Egbert J. E. G. Bast; Ronald J. M. Croughs

1995-01-01

115

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

116

Neurobehavioral alterations in autoimmune mice.  

PubMed

Inbred MRL, NZB and BXSB strains of mice spontaneously develop a systemic, lupus-like autoimmune disease. The progress of autoimmunity is accompanied with a cascade of behavioral changes, most consistently observed in tasks reflective of emotional reactivity and the two-way avoidance learning task. Given the possibility that behavioral alterations may reflect a detrimental consequence of autoimmune-inflammatory processes and/or an adaptive response to chronic malaise, they are tentatively labeled as autoimmunity-associated behavioral syndrome (AABS). It is hypothesized that neuroactive immune factors (pro-inflammatory cytokines, brain-reactive antibodies) together with endocrine mediators (corticotropin-releasing factor, glucocorticoids) participate in the etiology of AABS. Since AABS develops natively, and has a considerable face and predictive validity, and since the principal pathway to autoimmunity is known, AABS may be a useful model for the study of CNS involvement in human autoimmune diseases and by extension, for testing autoimmune hypotheses of several mental disorders (major depression, schizophrenia, Alzheimer's disease, autism and AIDS-related dementia). PMID:9168268

Saki?, B; Szechtman, H; Denburg, J A

1997-05-01

117

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

ERIC Educational Resources Information Center

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

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

2013-01-01

118

Autoimmune hepatitis  

Microsoft Academic Search

Autoimmune hepatitis (AIH) is a rare disease, characterized by female predominance, hypergammaglobulinemia, autoantibodies, association with HLA DR3 and HLA DR4 and a good response to immunosuppression. Different subtypes of AIH may be distinguished, based on differences in the autoantibody patterns. AIH type 1 is characterized by anti-nuclear (ANA) and\\/or anti-smooth muscular (SMA) autoantibodies. AIH type 2 is characterized by liver\\/kidney

Petra Obermayer-Straub; Christian P. Strassburg; Michael P. Manns

2000-01-01

119

Autoimmune Hepatitis  

Microsoft Academic Search

Autoimmune hepatitis (AIH) is an inflammatory liver disease with a strong female preponderance, characterized by elevated\\u000a levels of transaminases and immunoglobulin G (IgG), seropositivity for organ and non-organ-specific autoantibodies, and a\\u000a histological picture of interface hepatitis. The major pathogenic mechanism is believed to be immune reaction against host\\u000a liver antigens. AIH responds well to immuno-suppressive treatment. The diagnosis should be

Diego Vergani; Giorgina Mieli-Vergani

120

Autoimmune Encephalitis in Children  

PubMed Central

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

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

2013-01-01

121

Multiple Sclerosis and Other Autoimmune Diseases Irfan Jafree, MD; Komal Hashmi, MBBS; Samuel Landero, MD; Gustavo Suarez, MD;  

E-print Network

of autoimmune diseases in genetically susceptible populations. Coexistence of other autoimmune disorders with MSMultiple Sclerosis and Other Autoimmune Diseases Irfan Jafree, MD; Komal Hashmi, MBBS; Samuel supports the autoimmune hypothesis. Objectives: To look for co-occurrence of autoimmune diseases including

Lichtarge, Olivier

122

Activation of the Jak/Stat signalling pathway by leukaemia inhibitory factor stimulates trans-differentiation of human non-endocrine pancreatic cells into insulin-producing cells.  

PubMed

Differentiation of pancreatic ?-cells is regulated by a wide range of signalling pathways. The aim of our current work was to evaluate the effect of the Jak/Stat signalling pathway on the differentiation of human non-endocrine pancreatic cells into insulin-producing cells. Activation of the Jak/Stat signalling pathway by leukaemia inhibitory factor (LIF) stimulated differentiation of C-peptide-negative human non-endocrine pancreatic cells into insulin-producing cells in 6.3 ± 2.0 % cells (N = 5) and induced expression of pro-endocrine transcription factor neurogenin 3, Notch signalling pathway suppressor HES6 and stimulator of ?-cell neogenesis REG3A. The expression of the REG3A gene and increased rate of differentiation into insulin-producing cells (10.2 ± 2.1 %) were further stimulated by a combination of LIF with nicotinamide and dexamethasone. Glucose-stimulated (5 vs. 20 mM) C-peptide secretion confirmed proper insulin secretory function of trans-differentiated insulin-producing cells (0.51 vs. 2.03 pmol C-peptide/?g DNA, P < 0.05). Our results indicate that Jak/Stat signalling critically contributes to trans-differentiation of non-endocrine pancreatic cells into functional insulin-producing cells. The positive effect of the Jak/Stat signalling pathway on trans-differentiation is mediated by the key genes that activate differentiation of pancreatic ?-cells. PMID:22849859

Koblas, T; Leontovy?, I; Zacharovová, K; Berková, Z; K?íž, J; Girman, P; Saudek, F

2012-01-01

123

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

PubMed Central

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

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

2012-01-01

124

The thyroid and autoimmunity.  

PubMed

Autoimmune thyroid diseases (Hashimoto thyroiditis, Graves' disease, postpartum thyroiditis, atrophic thyroiditis and drug induced thyroiditis) are prevalent disorders worldwide, especially in women (related to the millieu of sex steroids and X chromosome effects on the thyroid and the immune system). Disruption of thyroid self tolerance, usually induced by an infection, generates abnormal thyroid--immune interactions, implicating an array of cytokines and their receptors. Thyrocytes achieve antigen presenting cell properties which stimulate effector immune cells (Th1, Th2, Th17), in the context of defective immunomodulatory T regulatory cells, resulting in thyroid lymphocytic infiltration and activation of B cells, with production of antibodies against thyroid antigens, thyroid destruction or stimulation, depending on the Th1-Th2 balance. During pregnancy there is a Th2 predominance sustained by the increased glucocorticoid, estrogen and progesteron levels, which allows tolerance versus the histoincompatible fetoplacental unit. In the postpartum period, the return shift Th2 to Th1 favors the occurrence of postpartum thyroiditis. Altered thyroid hormone levels can influence the immune system, and, on the other side, some immune cells secrete TSH, which exerts endocrine and paracrine, cytokine-like effects. Understanding the complex pathogenesis of autoimmune thyroid disorders is crucial for prevention and management. PMID:20446435

Lichiardopol, Corina; Mo?a, Maria

2009-01-01

125

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

126

Autoimmune pancreatitis mimicking pancreatic cancer  

PubMed Central

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

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

2011-01-01

127

Novel Associations for Hypothyroidism Include Known Autoimmune Risk Loci  

E-print Network

autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top associationNovel Associations for Hypothyroidism Include Known Autoimmune Risk Loci Nicholas Eriksson*, Joyce disorder, affecting about 5% of the general population. Here we present the current largest genome

Li, Fei-Fei

128

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

129

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. Rønningen; 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

130

Autoimmune Disease Prevalence in a Multiple Sclerosis Cohort in Argentina  

PubMed Central

Background. Comorbid autoimmune diseases in MS patients have been studied extensively with controversial results. Moreover, no such data exists for Latin-American MS patients. Methods. We conducted a case-control study aimed to establish the prevalence of autoimmune disorders in a cohort of Argentinean MS patients. Results. There were no significant differences in autoimmune disease prevalence in MS patients with respect to controls. The presence of one or more autoimmune disorders did not increase risk of MS (OR 0.85, 95%?CI 0.6–1.3). Discussion. Our results indicate absence of increased comorbid autoimmune disease prevalence in MS patients, as well as of increased risk of MS in patients suffering from other autoimmune disorders. PMID:25170425

Farez, Mauricio F.; Balbuena Aguirre, Maria E.; Varela, Francisco; Kohler, Alejandro A.

2014-01-01

131

Autoimmune disorders after immunisation with Influenza A/H1N1 vaccines with and without adjuvant: EudraVigilance data and literature review.  

PubMed

All suspected autoimmune disorders (AID) reported as adverse reactions to EudraVigilance from 1 October 2009 to 31 December 2010 for adjuvanted (Celtura™, Fluval P™, Focetria™ and Pandemrix™) and non-adjuvanted (Cantgrip™, Celvapan™ and Panenza™) pandemic Influenza A/H1N1 vaccines were analysed to determine whether adjuvanted vaccines were associated with higher reporting of AID than non-adjuvanted ones. AID were identified based on the corresponding MedDRA High Level Group Term. Reports of type 1 diabetes mellitus and multiple sclerosis were also included in the analysis. Causality was assessed based on WHO causality assessment for adverse events following immunisation and Brighton Collaboration criteria for Guillain-Barré syndrome (GBS), idiopathic thrombocytopenic purpura and acute disseminated encephalomyelitis. Of the 50,221 adverse reactions received in EudraVigilance for A/H1N1 vaccines (adjuvanted: 46,173, non-adjuvanted: 4048), 314 were AID (adjuvanted: 276, non-adjuvanted: 38). GBS was the AID with the highest number of reports (125, adjuvanted: 109, non-adjuvanted: 16). Reporting ratios as calculated by the percentages of AID amongst all reported adverse reactions were 0.60% (95% CI: 0.53-0.67) and 0.94% (95% CI: 0.64-1.24) for adjuvanted and non-adjuvanted vaccines, and were 0.26% (95% CI: 0.22-0.31) and 0.37% (95% CI: 0.18-0.56) in a restricted analysis based on diagnostic certainty, causal relationship and plausible temporal association. Reporting rates for all reports of AID using the estimated number of vaccinees as denominator were 6.87 (95% CI: 6.06-7.68) and 9.98 (95% CI: 6.81-13.16) per million for adjuvanted and non-adjuvanted vaccines, and 3.01 (95% CI: 2.47-3.55) and 3.94 (95% CI: 1.95-5.94) per million in the restricted analysis. These results do not suggest a difference in the reporting of AID between adjuvanted and non-adjuvanted A/H1N1 vaccines. In a literature review performed on 31 August 2011, GBS was also the AID the most frequently discussed in association with A/H1N1 vaccination; reporting rates were generally within expected background rates. PMID:23022149

Isai, Alina; Durand, Julie; Le Meur, Steven; Hidalgo-Simon, Ana; Kurz, Xavier

2012-11-19

132

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

133

Autoimmune Thyroiditis in Childhood  

PubMed Central

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

Brown, Rosalind S.

2013-01-01

134

Approximately one million individuals worldwide suf-fer from multiple sclerosis, an autoimmune disease that  

E-print Network

Approximately one million individuals worldwide suf- fer from multiple sclerosis, an autoimmune defects can involve problems with vision, sensation, motor func- tion or autonomic disorders of bowel sclerosis, collectively known as experimental autoimmune encephalomyelitis (EAE), have both progressive

Cai, Long

135

Cytokines in Autoimmune Uveitis  

PubMed Central

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

Horai, Reiko

2011-01-01

136

Variant forms of autoimmune hepatitis  

Microsoft Academic Search

Variant forms of autoimmune hepatitis have features that are intermixed with another disorder (overlap syndrome) or findings\\u000a that are inconsistent with or insufficient for a confident diagnosis of classic disease (outlier syndrome). Diagnostic criteria\\u000a have not been codified, but application of a modified scoring system provides a template that can be combined with clinical\\u000a findings to ensure uniform evaluation and

Albert J. Czaja

1999-01-01

137

Adult autoimmune enteropathy  

PubMed Central

Recent reports have suggested that autoimmune enteropathy involving the small bowel may occur in adults as well as in children. Apparently, the endoscopic and histological changes are similar to celiac disease before treatment, but these are not altered by any form of dietary restriction, including a gluten-free diet. As in celiac disease, histologic changes in gastric and colonic biopsies have also been recorded. Anti-enterocyte antibodies detected with immunofluorescent methods have been reported by a few laboratories, but these antibodies appear not to be specific and may simply represent epiphenomena. A widely available, reproducible and quantitative anti-enterocyte antibody assay is needed that could be applied in small bowel disorders that have the histological appearance of celiac disease, but fail to respond to a gluten-free diet. PMID:18300339

Freeman, Hugh James

2008-01-01

138

Pathogen infection as a possible cause for autoimmune hepatitis.  

PubMed

Autoimmune disorders afflicting the liver comprise the bona fide autoimmune diseases, primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis as well as drug-induced autoimmune-like diseases, such as halothane hepatitis. Whereas drug-induced forms of acute or chronic hepatitis often have a clear triggering factor, the etiology of classical autoimmune liver diseases is only poorly understood. Besides a genetic component present in disease susceptible individuals, environmental triggering factors are likely to play a role in the initiation and/or propagation of the disease. In this article, we will review on current evidence obtained from epidemiological associations, case studies, and findings in animal models for pathogens, to be involved in the etiology of autoimmune liver disease with a special focus on autoimmune hepatitis. PMID:24911790

Christen, Urs; Hintermann, Edith

2014-01-01

139

Toxicology of Autoimmune Diseases  

PubMed Central

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

Hultman, Per; Kono, Dwight H.

2010-01-01

140

Plasmapheresis and Autoimmune Disease  

MedlinePLUS

... the booklet in this Web page . Plasmapheresis and Autoimmune Disease Many diseases, including myasthenia gravis, Lambert-Eaton syndrome, ... tissues has been the most common approach to autoimmune disease for more than 30 years. Many new immunosuppressants ...

141

Are Dysregulated Inflammatory Responses to Commensal Bacteria Involved in the Pathogenesis of Hepatobiliary-Pancreatic Autoimmune Disease? An Analysis Using Mice Models of Primary Biliary Cirrhosis and Autoimmune Pancreatitis  

PubMed Central

The etiopathogenesis of many autoimmune disorders has not been identified. The aim of this paper is to focus on the involvement of bacterial exposure in the pathogenesis of primary biliary cirrhosis (PBC) and autoimmune pancreatitis (AIP), both of which are broadly categorized as autoimmune disorders involving hepatobiliary-pancreatic lesions. Avirulent and/or commensal bacteria, which may have important role(s) as initiating factors in the pathogenesis of autoimmune disorders such as PBC and AIP, will be emphasized. PMID:21991516

Yanagisawa, Naoko; Haruta, Ikuko; Kikuchi, Ken; Shibata, Noriyuki; Yagi, Junji

2011-01-01

142

Cholestatic phenotypes of autoimmune hepatitis.  

PubMed

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

Czaja, Albert J

2014-09-01

143

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

144

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

145

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

146

HIV and autoimmunity  

Microsoft Academic Search

The association of immune dysfunction in patients with human immunodeficiency virus (HIV) infection and AIDS and the development of autoimmune diseases is intriguing. Yet, the spectrum of reported autoimmune phenomena in these patients is increasing. An infectious trigger for immune activation is one of the postulated mechanisms and derives from molecular mimicry. During frank loss of immunocompetence, autoimmune diseases that

Gisele Zandman-Goddard; Yehuda Shoenfeld

2002-01-01

147

Autoimmunity in thyroid disease  

Microsoft Academic Search

The autoimmune thyroid diseases, Graves' disease and autoimmune hypothyroidism, represent the two ends of a disease spectrum where an immune response is directed against the thyroid gland. In Graves' disease, antibodies directed against the thyrotropin receptor (TSH-R) lead to the development of glandular overactivity, while in autoimmune hypothyroidism, cell-mediated and humoral thyroid injury leads to destruction of thyroid tissue and

Joanne Collins; Stephen Gough

2002-01-01

148

Immune-Endocrine Interactions in Autoimmune Thyroid Diseases  

Microsoft Academic Search

Autoimmune thyroid diseases (AITD) are the most common organ-specific autoimmune disorders affecting approximately 5% of the overall population. An aberrant interaction between abnormal thyrocytes, abnormal antigen-presenting cells and abnormal T cells forms the basis for the atypical autoimmune reaction targeting thyroid antigens. It was proposed that nongenetic (environmental and hormonal) factors play a crucial etiological role in AITD development, through

Alicia Juana Klecha; María Laura Barreiro Arcos; Luciana Frick; Ana María Genaro; Graciela Cremaschi

2008-01-01

149

Autoimmunity-Related Granulomatous Dermatitis in Association with Hepatitis  

Microsoft Academic Search

Aim: Both interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic granulomatous dermatitis (PNGD) are rare disorders typically associated with systemic autoimmune conditions. They probably represent different aspects of a disease spectrum encompassing the concept of autoimmunity-related granulomatous dermatitis (ARGD). Case Report: A 61-year-old woman presented with ARGD and autoimmune hepatitis. The clinical presentation suggested PNGD, while histopathology was consistent with IGD.

Grégory Szepetiuk; Marianne Lesuisse; Gérald E. Piérard; Pascale Quatresooz; Claudine Piérard-Franchimont

2012-01-01

150

Identification of autoimmune gene signatures in autism.  

PubMed

The role of the immune system in neuropsychiatric diseases, including autism spectrum disorder (ASD), has long been hypothesized. This hypothesis has mainly been supported by family cohort studies and the immunological abnormalities found in ASD patients, but had limited findings in genetic association testing. Two cross-disorder genetic association tests were performed on the genome-wide data sets of ASD and six autoimmune disorders. In the polygenic score test, we examined whether ASD risk alleles with low effect sizes work collectively in specific autoimmune disorders and show significant association statistics. In the genetic variation score test, we tested whether allele-specific associations between ASD and autoimmune disorders can be found using nominally significant single-nucleotide polymorphisms. In both tests, we found that ASD is probabilistically linked to ankylosing spondylitis (AS) and multiple sclerosis (MS). Association coefficients showed that ASD and AS were positively associated, meaning that autism susceptibility alleles may have a similar collective effect in AS. The association coefficients were negative between ASD and MS. Significant associations between ASD and two autoimmune disorders were identified. This genetic association supports the idea that specific immunological abnormalities may underlie the etiology of autism, at least in a number of cases. PMID:22832355

Jung, J-Y; Kohane, I S; Wall, D P

2011-01-01

151

Autoimmune blistering dermatoses as systemic diseases.  

PubMed

Autoimmune blistering dermatoses are examples of skin-specific autoimmune disorders that can sometimes represent the cutaneous manifestation of a multiorgan disease due to potential common pathogenic mechanisms. As soon as a distinct autoimmune blistering dermatosis is diagnosed, it is imperative to consider its potential systemic involvement, as well as the autoimmune and inflammatory conditions that are frequently associated with it. In paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, the internal organs (particularly the lungs) are affected by the autoimmune injury. Pemphigus erythematosus may manifest with overlapping serologic and immunohistologic features of lupus erythematosus. In patients with bullous pemphigoid, there is a greater prevalence of neurologic disease, possibly caused by cross-reactivity of the autoantibodies with isoforms of bullous pemphigoid antigens expressed in the skin and brain. Anti-laminin 332 pemphigoid shows an increased risk for adenocarcinomas. Patients with anti-p200 pemphigoid often suffer from psoriasis. A rare form of pemphigoid with antibodies against the ?5 chain of type IV collagen is characterized by underlying nephropathia. Particularly interesting is the association of linear IgA disease or epidermolysis bullosa acquisita with inflammatory bowel disease. Dermatitis herpetiformis is currently regarded as the skin manifestation of gluten sensitivity. Bullous systemic lupus erythematosus is part of the clinical spectrum of systemic lupus erythematosus, a prototypic autoimmune disease with multisystem involvement. PMID:24767184

Vassileva, Snejina; Drenovska, Kossara; Manuelyan, Karen

2014-01-01

152

The role of innate immune responses in autoimmune disease development  

Microsoft Academic Search

Autoimmune diseases are systemic or organ-specific disorders that are the result of an attack of the immune system against the body's own tissue. Development of autoimmune disease is generally avoided by distinct mechanisms that silence adaptive self-reactive T or B cells. The innate immune system is critically involved in the defense against pathogens and the induction of primary adaptive immune

Hanspeter Waldner

2009-01-01

153

Text-mining applied to autoimmune disease research: the Sjögren¿s syndrome knowledge base  

E-print Network

of the most common autoimmune disorders in the U.S. , withautoimmune disease research: the Sjögren’s syndrome knowledge base. BMC Musculoskeletal DisordersDisorders 2012, 13:119 http://www.biomedcentral.com/1471-2474/13/119 RESEARCH ARTICLE Open Access Text-mining applied to autoimmune

Gorr, Sven-Ulrik; Wennblom, Trevor J; Horvath, Steve; Wong, David TW; Michie, Sara A

2012-01-01

154

Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 (APS1)  

Microsoft Academic Search

Thymomas are thymic epithelial neoplasms, associated with a variety of autoimmune disorders (especially myasthenia gravis), that apparently result from aberrant intra- tumourous thymopoiesis and export of inefficiently tolerized T-cells to the periphery. The autoimmune regulator (AIRE) drives the expression of self-antigens in the thymic medulla and plays an essential role in 'central' tolerance in both humans and mice. However, while

P Ströbel; A Murumägi; R Klein; M Luster; M Lahti; K Krohn; B Schalke; W Nix; R Gold; P Rieckmann; K Toyka; C Burek; A Rosenwald; HK Müller-Hermelink; R Pujoll-Borrell; A Meager; N Willcox; P Peterson; A Marx

2007-01-01

155

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

2014-02-03

156

Autoimmune diseases and autoimmunity post-bone marrow transplantation  

Microsoft Academic Search

BMT can both transmit and eliminate autoimmune diseases, and hence it has been suggested as an optional treatment for severe autoimmune conditions. In this communication we deal with the question of whether chronic GVHD is an autoimmune disease in itself, review the literature reports of autoimmune diseases following BMT in humans, and describe the autoimmune nature of the post-BMT state.

Y Sherer; Y Shoenfeld

1998-01-01

157

Autoimmunity-Related Granulomatous Dermatitis in Association with Hepatitis  

PubMed Central

Aim Both interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic granulomatous dermatitis (PNGD) are rare disorders typically associated with systemic autoimmune conditions. They probably represent different aspects of a disease spectrum encompassing the concept of autoimmunity-related granulomatous dermatitis (ARGD). Case Report A 61-year-old woman presented with ARGD and autoimmune hepatitis. The clinical presentation suggested PNGD, while histopathology was consistent with IGD. Discussion The association of ARGD with autoimmune hepatitis is apparently a rare event. The present case shows that the clinicopathological correlation in ARGD does not always clearly fit with the classical presentations of IGD or PNGD. PMID:22649335

Szepetiuk, Gregory; Lesuisse, Marianne; Pierard, Gerald E.; Quatresooz, Pascale; Pierard-Franchimont, Claudine

2012-01-01

158

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

159

Autoimmunity associated with infection: leprosy, acute rheumatic fever and Lyme disease.  

PubMed

This review examines the links between autoimmunity and three common infectious diseases. These disorders are associated with a variety of clinical and serological autoimmune phenomena. In addition they might conceivably trigger autoimmune diseases themselves. Mechanisms that may be responsible for these links, including molecular mimicry, are explored. PMID:1793538

Ehrenstein, M; Isenberg, D

1991-12-01

160

Autoimmune pathology accounts for common manifestations in a wide range of neuro-psychiatric disorders: the olfactory and immune system interrelationship.  

PubMed

Smell has traditionally been considered a less important sense when compared to sight or hearing, but recent research has unraveled important features inherent to the sense of smell. Once considered just a chemical sensor for sampling the environment, data from animal models and human studies currently imply numerous and complex effects of smell on behavior, mood, and on the immune response. In this review we discuss a possible inter-relationship between olfactory impairment, autoimmunity and neurological/psychiatric symptoms in several diseases affecting the central nervous system (CNS) such as Parkinson, Alzheimer's disease, autism, schizophrenia, multiple sclerosis and neuropsychiatric lupus erythematosus. We suggest that common manifestations are not mere coincidences. Current data from animal models show that neuropsychiatric manifestations are intimately associated with smell impairment, and autoimmune dysregulation, via autoantibodies (anti-NMDAR, anti-ribosomal P) or other mechanisms. From clues of pathological manifestations, we propose a novel approach to the understanding of the interactions between the CNS, the smell and the immune system. PMID:19097945

Moscavitch, Samuel-Datum; Szyper-Kravitz, Martine; Shoenfeld, Yehuda

2009-03-01

161

Autoimmune pancreatitis: A review  

PubMed Central

Autoimmune pancreatitis has emerged over the last 40 years from a proposed concept to a well established and recognized entity. As an efficient mimicker of pancreatic carcinoma, its early and appropriate recognition are crucial. With mounting understanding of its pathogenesis and natural history, significant advances have been made in the diagnosis of autoimmune pancreatitis. The characteristic laboratory features and imaging seen in autoimmune pancreatitis are reviewed along with some of the proposed diagnostic criteria and treatment algorithms. PMID:18081220

Zandieh, Iman; Byrne, Michael F

2007-01-01

162

Family history of autoimmune diseases in psychosis  

Microsoft Academic Search

The mothers of 101 psychotic patients and 116 normal controls were interviewed using a semi-structured questionnaire designed to determine the presence or absence of autoimmune disorders in first degree relatives of the probands. Thyrotoxicosis and insulin-dependent diabetes mellitus were significantly more common in the relatives of the psychotic patients than in the control relatives; in particular thyrotoxicosis was more frequent

Catherine M. Gilvarry; Pak C. Sham; Peter B. Jones; Mary Cannon; Padraig Wright; Shon W. Lewis; Paul Bebbington; Brian K. Toone; Robin M. Murray

1996-01-01

163

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.

164

Autoimmune primary ovarian insufficiency.  

PubMed

Primary ovarian insufficiency (POI) is defined as sustained amenorrhea, increased follicle-stimulating hormone and low estrogen levels, whereas diminished ovarian reserve (DOR) is characterized as regular menses and alterations of ovarian reserve tests. POI of autoimmune origin may be associated with adrenal autoimmunity, non-adrenal autoimmunity or isolated. This autoimmune disease is characterized by serum ovarian, adrenocortical or steroidogenic cell autoantibodies. POI of adrenal autoimmune origin is the most frequent type observed in 60-80% of patients. Clinically, amenorrhea is the hallmark of POI, however before menstruation stops completely, irregular cycles occur. Infertility, hot flushes, vaginal atrophy, and dyspareunia are also common. Autoimmune oophoritis is characterized by mononuclear inflammatory cell infiltrate in the theca cells of growing follicles, with early stage follicles without lymphocytic infiltration. This infiltrate includes plasma, B and T-cells. A novel classification criterion for autoimmune POI/DOR is proposed subdividing in three distinct categories (possible, probable and confirmed) according to autoantibodies, autoimmune disease and ovarian histology. Unfortunately, up to date guidelines for the treatment of autoimmune oophoritis are not available. Strategies to POI treatment include hormone replacement and infertility therapy. Assisted conception with donated oocytes has been proven to achieve pregnancy by intra cytoplasmic sperm injection in POI women. PMID:24418305

Silva, C A; Yamakami, L Y S; Aikawa, N E; Araujo, D B; Carvalho, J F; Bonfá, E

2014-01-01

165

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

PubMed Central

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

Betterle, C; Lazzarotto, F; Presotto, F

2004-01-01

166

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

167

Autoimmunity and the Gut  

PubMed Central

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

Campbell, Andrew W.

2014-01-01

168

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

169

CTLA-4 in autoimmune diseases – a general susceptibility gene to autoimmunity?  

Microsoft Academic Search

For most autoimmune disorders, the pattern of inheritance is very complex. The major histocompatibility complex (MHC) gene complex has been implicated as the major genetic component in the predisposition to these diseases but other genes are likely to be involved. Based on function and experimental data, the gene encoding cytotoxic T lymphocyte-associated antigen 4 (CTLA4) has been suggested as a

OP Kristiansen; ZM Larsen; F Pociot

2000-01-01

170

Autoimmune diseases in gastroenterology.  

PubMed

There are several different diseases in gastroenterology with an important role of immunological mechanisms in their pathogenesis. We know autoimmune diseases with immunological reactions against liver or pancreatic tissue. In addition there are diseases like chronic inflammatory bowel diseases representing inappropriate immunological reactions followed by inflammation and tissue destruction. The research of the last decade has contributed significantly to the understanding of the pathogenesis of diseases based on immunological mechanisms and consequently to the development of novel therapeutic strategies targeting molecules. Chronic inflammatory bowel diseases, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, autoimmune pancreatitis, and celiac disease are the most important diseases with immunological pathogenesis in Gastroenterology. Especially in chronic inflammatory bowel diseases ulcerative colitis and Crohn's disease with immunosuppressive drugs and monoclonal antibodies new preparations are used in therapy. Autoimmune pancreatitis was characterized as an own entity in the last years. Therefore, this review will focus on these diseases. PMID:22612745

Emmrich, Joerg; Jaster, Robert

2012-01-01

171

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

172

Age-related autoimmunity.  

PubMed

Older persons have higher autoimmunity but a lower prevalence of autoimmune diseases. A possible explanation for this is the expansion of many protective regulatory mechanisms highly characteristic in the elderly. Of note is the higher production of peripheral T-regulatory cells.The frequent development of autoimmunity in the elderly was suggested to take place in part due to the selection of T cells with increased affinity to self-antigens or to latent viruses. These cells were shown to have a greater ability to be pro-inflammatory, thereby amplifying autoimmunity. During aging, thymic T-regulatory cell output decreases in association with the loss of thymic capacity to generate new T cells. However, to balance the above mentioned autoimmunity and prevent the development of autoimmune diseases, there is an age-related increase in peripheral CD4+ CD25highFoxP3+ T-regulatory cells. It remains unclear whether this is an age-related immune dysfunction or a defense response. Whatever the reason, the expansion of T-regulatory cells requires payment in terms of an increased incidence of cancer and higher susceptibility to infections. PMID:23556986

Vadasz, Zahava; Haj, Tharwat; Kessel, Aharon; Toubi, Elias

2013-01-01

173

The epigenetics of autoimmunity  

PubMed Central

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

2011-01-01

174

Autoimmunity in 2013.  

PubMed

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

Selmi, Carlo

2014-08-01

175

A Comprehensive Analysis of Shared Loci between Systemic Lupus Erythematosus (SLE) and Sixteen Autoimmune Diseases Reveals Limited Genetic Overlap  

Microsoft Academic Search

In spite of the well-known clustering of multiple autoimmune disorders in families, analyses of specific shared genes and polymorphisms between systemic lupus erythematosus (SLE) and other autoimmune diseases (ADs) have been limited. Therefore, we comprehensively tested autoimmune variants for association with SLE, aiming to identify pleiotropic genetic associations between these diseases. We compiled a list of 446 non–Major Histocompatibility Complex

Paula S. Ramos; Lindsey A. Criswell; Kathy L. Moser; Mary E. Comeau; Adrienne H. Williams; Nicholas M. Pajewski; Sharon A. Chung; Robert R. Graham; Raphael Zidovetzki; Jennifer A. Kelly; Kenneth M. Kaufman; Chaim O. Jacob; Timothy J. Vyse; Betty P. Tsao; Robert P. Kimberly; Patrick M. Gaffney; Marta E. Alarcón-Riquelme; John B. Harley; Carl D. Langefeld

2011-01-01

176

Inverse correlation between the incidences of autoimmune disease and infection predicted by a model of T cell mediated tolerance  

Microsoft Academic Search

The contribution of pathogenic infections to the etiology of autoimmune diseases remains one of the outstanding problems in immunology. According to the classical concept of antigen mimicry, a direct correlation between the incidence of autoimmunity and infections would be expected. This view is supported by a few examples of autoimmune disorders, which are documented as being caused by infection with

Kalet León; Jose Faro; Agustin Lage; Jorge Carneiro

2004-01-01

177

Insights into type 1 diabetes from the autoimmune polyendocrine syndromes  

PubMed Central

Purpose of review: Advances in human genetics and investigations in animal models of autoimmune disease have allowed insight into the basic mechanisms of immunologic tolerance. These advances allow us to understand the pathogenesis of Type 1 diabetes and other autoimmune diseases as never before. Here, we discuss the tolerance mechanisms of the autoimmune polyendocrine syndromes and their relevance to Type 1 diabetes. Recent findings: Defects in central tolerance with alteration of self-antigen expression levels in the thymus are a potent cause of autoimmunity. Peripheral tolerance defects that alter T cell activation and signaling also play an important role in the pathogenesis of diabetes and other associated autoimmune disorders, with multiple modest defects working in concert to produce disease. Regulation of the immune response through the action of regulatory T cells is a potent mode of tolerance induction in autoimmunity that is important in Type 1 diabetes. Summary: Rare syndromes of autoimmunity provide a valuable window into the breakdown of tolerance and identify multiple checkpoints that are critical for generation of autoimmunity. Understanding the application of these in Type 1 diabetes will allow the development of future immunomodulatory therapies in the treatment and prevention of disease. PMID:23770732

Cheng, Mickie; Anderson, Mark S.

2014-01-01

178

Autoimmune polyendocrine syndromes: clues to type 1 diabetes pathogenesis  

PubMed Central

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

Husebye, Eystein S.; Anderson, Mark S.

2010-01-01

179

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

180

[Research update on pathogenesis of autoimmune thyroid diseases].  

PubMed

Autoimmune thyroid disease (AITD) is the typical organ-specific autoimmune disorder. However, the underlying molecular mechanisms by which immune reactions against specific thyroid proteins are induced are still largely unknown. Accumulated evidence from animal models has generated new insights into the pathogenesis of AITD. Recent studies have indicated that innate immune responses induced by both exogenous and endogenous factors affect the phenotype and severity of autoimmune reactions. One of the recent topics is the effect of self genomic DNA fragments on immune activation. Here we review by focusing on the possible role of innate immune activation in the development of AITD. PMID:23214056

Suzuki, Koichi; Kawashima, Akira; Kimura, Hiroaki

2012-11-01

181

Kriterier for diagnose og behandling av autoimmune leversykdommer. Gjennomgang av pasientmateriale i tiden 2000-2006 ved Gastromedisinsk avdeling, Ullevål Universitetssykehus.  

E-print Network

??Abstract Objectives/background/method Autoimmune liver disorders include autoimmune hepatitis (AIH), primary biliary cirrosis (PBC) and primary sclerosing cholangitis (PSC). The purpose of this study was to… (more)

Grøndalen, Ingvild Marie

2008-01-01

182

Resolution of Autoimmune Oophoritis after Thymectomy in a Myasthenia Gravis Patient  

PubMed Central

Myasthenia gravis (MG) is an autoimmune disorder characterized by autoantibodies against acetylcholine receptors. MG is generally an isolated disorder but may occur concomitantly with other autoimmune diseases. We describe an eighteen-year-old girl with MG who was admitted to our clinic with secondary amenorrhea and diagnosed as autoimmune oophoritis. Since her myasthenic symptoms did not resolve with anticholinesterase therapy, thymectomy was performed. After thymectomy, her menses have been regular without any hormonal replacement therapy. To our knowledge, this is the first report on a patient with autoimmune ovarian insufficiency and MG in whom premature ovarian insufficiency resolved after thymectomy, without hormonal therapy. Conflict of interest:None declared. PMID:22155465

Ozdemir, Ozlem; Eren, Erdal; Saglam, Halil; Okan, Mehmet; Tar?m, Omer Faruk

2011-01-01

183

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

184

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

185

Interferon-? and Systemic Autoimmunity  

PubMed Central

The term interferon describes a family of proteins consisting of three major types (I, II, III) which differ in their primary protein sequences, cognate receptors, genetic loci, and cell types responsible for their production. The interferons, especially types I and II, overlap significantly in the genes they control resulting in a shared spectrum of diverse biological effects which includes regulation of both the innate and adaptive immune responses. As such, the interferons are major effectors in the pathogenesis of autoimmunity, especially systemic autoimmunity. The type I IFNs, because they are produced during the early stages of the innate immune response, are thought to play the foremost role in autoimmune responses. However, numerous studies have found that the single type II IFN, IFN-?, plays an essential role in the development and severity of systemic autoimmunity, particularly systemic lupus erythematosus. This is supported by animal studies where IFN-? is uniformly required in both spontaneous and induced models of lupus. Although expression of IFN-? in cells of the innate immune system is almost immediate after activation, expression in adaptive immunity requires a complex orchestration of cellular interactions, signaling events and epigenetic modifications. The multifaceted nature of IFN-? in adaptive immunity identifies numerous possible therapeutic targets that, because of the essential contribution of IFN-? to systemic autoimmunity, have the potential for producing significant benefits. PMID:23998448

Pollard, K.M.; Cauvi, D.M.; Toomey, C.B; Morris, K.V.; Kono, D.H.

2014-01-01

186

Autoimmunity and asbestos exposure.  

PubMed

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

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

2014-01-01

187

Autoimmunity and Asbestos Exposure  

PubMed Central

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

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

2014-01-01

188

American Autoimmune Related Diseases Association  

MedlinePLUS

... MA – “What Every American Need to Know About Autoimmune Disease” on Saturday, November 15, 2014 from 10:00- ... speakers are Dr. Noel Rose, head of the Autoimmune Disease Research Center at Johns Hopkins, speaking about “What ...

189

Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation.  

PubMed

Autologous stem cell transplantation with or without in vitro lymphocyte depletion has been suggested as a new treatment option for severe autoimmune diseases. We describe five patients with autoimmune diseases (CREST syndrome, myasthenia gravis and Hashimoto's thyroiditis, systemic lupus erythematosus, atopic dermatitis, and rheumatoid arthritis) who underwent autologous bone marrow (n = 1) or peripheral blood progenitor cell (n = 4) transplantation with unmanipulated grafts as treatment for the autoimmune disease in one case or as treatment for a malignant disorder with a concomitant autoimmune disorder in four cases. In all patients serological and clinical signs of the autoimmune disease recurred early or persisted. These observations should be regarded as a cautionary note concerning the efficacy of high-dose therapy followed by transplantation of unmanipulated autologous stem cells for treatment of severe autoimmune diseases. PMID:8896432

Euler, H H; Marmont, A M; Bacigalupo, A; Fastenrath, S; Dreger, P; Hoffknecht, M; Zander, A R; Schalke, B; Hahn, U; Haas, R; Schmitz, N

1996-11-01

190

Autoimmune blistering skin diseases.  

PubMed

Emergency physicians, at the front line of patient care, are often confronted with a wide variety of dermatologic conditions. Prompt recognition is essential, especially for the autoimmune blistering skin diseases, many of which have considerable morbidity and mortality. Therefore, an accurate diagnosis is imperative for appropriate referral and initiation of therapy. This review article provides a concise yet thorough discussion of the clinical presentation, incidence, differential diagnosis and management of the commonly encountered autoimmune blistering skin diseases, some of which include pemphigus, bullous pemphigoid, and epidermolysis bullosa acquisita. PMID:10830686

Cotell, S; Robinson, N D; Chan, L S

2000-05-01

191

B cells in autoimmunity  

PubMed Central

B-cell development is tightly regulated, including the induction of B-cell memory and antibody-secreting plasmablasts and plasma cells. In the last decade, we have expanded our understanding of effector functions of B cells as well as their roles in human autoimmune diseases. The current review addresses the role of certain stages of B-cell development as well as plasmablasts/plasma cells in immune regulation under normal and autoimmune conditions with particular emphasis on systemic lupus erythematosus. Based on preclinical and clinical data, B cells have emerged increasingly as both effector cells as well as cells with immunoregulatory potential. PMID:19849820

2009-01-01

192

Immunologic Endocrine Disorders  

PubMed Central

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

Michels, Aaron W.; Eisenbarth, George S.

2010-01-01

193

Programmed death-1 (PD-1)/PD-1 ligand pathway-mediated immune responses against human T-lymphotropic virus type 1 (HTLV-1) in HTLV-1-associated myelopathy/tropical spastic paraparesis and carriers with autoimmune disorders.  

PubMed

Human T-lymphotropic virus-1 (HTLV-1) causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia-lymphoma in individuals with dysfunctional immune responses. In this study, to characterize the HTLV-1-specific cytotoxic T lymphocyte (CTL) populations in asymptomatic HTLV-1 carriers (ACs), HAM/TSP patients, and carriers with autoimmune disorders (CAIDs), we examined the role of programmed death-1 and its ligand (PD-1/PD-L1) in HTLV-1-specific CTL functions using an HTLV-1 Tax/HLA-A*0201 tetramer and an HTLV-1 Tax/HLA-A*2402 tetramer. Interestingly, the percentage of HTLV-1 Tax301-309/HLA-A*2402 tetramer(+)CD8(+) cells expressing PD-1 in ACs was significantly higher than the percentage of HTLV-1 Tax11-19/HLA-A*0201 tetramer(+)CD8(+) cells expressing PD-1. PD-1 expression was significantly downregulated on HTLV-1-specific CTLs in HAM/TSP compared with ACs. PD-L1 expression was observed in a small proportion of unstimulated lymphocytes from ACs and was greater in ACs than in HAM/TSP and CAIDs after short-term culture. Furthermore, CTL degranulation was impaired in HAM/TSP, whereas anti-PD-L1 blockade significantly increased CTL function in ACs. Downregulation of PD-1 on HTLV-1-specific CTLs and loss of PD-L1 expression in HAM/TSP and CAIDs, along with impaired function of HTLV-1-specific CTLs in HAM/TSP, may underlie the apparently dysfunctional immune response against HTLV-1. PMID:21851845

Kozako, Tomohiro; Yoshimitsu, Makoto; Akimoto, Masaki; White, Yohann; Matsushita, Kakushi; Soeda, Shinji; Shimeno, Hiroshi; Kubota, Ryuji; Izumo, Shuji; Arima, Naomichi

2011-11-01

194

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

195

Thyroid Disorders Overview  

MedlinePLUS

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

196

Autoimmune blistering skin diseases  

Microsoft Academic Search

Emergency physicians, at the front line of patient care, are often confronted with a wide variety of dermatologic conditions. Prompt recognition is essential, especially for the autoimmune blistering skin diseases, many of which have considerable morbidity and mortality. Therefore, an accurate diagnosis is imperative for appropriate referral and initiation of therapy. This review article provides a concise yet thorough discussion

Stephanie Cotell; Neha D Robinson; Lawrence S Chan

2000-01-01

197

Autoimmune hepatitis, cryoglobulinaemia and untreated coeliac disease: a case report.  

PubMed

The clinical presentation of adult coeliac disease is often uncharacteristic, with extraintestinal symptoms being the main findings. We report a 48-year-old woman who presented with type II, hepatitis-C-negative cryoglobulinaemia, elevated liver enzymes, and iron deficiency. Antinuclear antibodies were positive, and immunoglobulin G (IgG) levels were elevated. On liver biopsy, a diagnosis of type I autoimmune hepatitis with a possible autoimmune cholangitis overlap syndrome was made. Immunosuppressive treatment led to a normalization of transaminase levels and resolved the cryoglobulinaemic vasculitis. In addition, the patient exhibited low ferritin and iron levels, which led to the diagnosis of coeliac disease. Long-standing, untreated coeliac disease is recognized to be a trigger for autoimmune disorders and is known to be associated with other autoimmune diseases, but the association with autoimmune hepatitis or autoimmune cholangitis is reported rarely. We conclude that in patients with autoimmune liver disease and unspecific clinical signs, such as iron deficiency, coeliac disease must be ruled out. PMID:12655265

Biecker, Erwin; Stieger, Muriel; Zimmermann, Arthur; Reichen, Jürg

2003-04-01

198

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

199

The Open Autoimmunity Journal, 2009, 1, 00-00 1 1876-8946/09 2009 Bentham Open  

E-print Network

in different diseases such as autoimmune diseases [5-8], cardiovascular disorders [9, 10] and cancer [11The Open Autoimmunity Journal, 2009, 1, 00-00 1 1876-8946/09 2009 Bentham Open Open Access Blood. They were suggested to play an important role in many diseases including autoim- mune disorders, however

Iglic, Ales

200

Modulation of autoimmune diseases by iPS cells.  

PubMed

Autoimmune disease is typically caused by the activated self-reacted immune cells. The mainstream treatment to autoimmune disorders is composed of different mechanisms of immunosuppression. In recent years, a new subtype of T cells called regulatory T (Treg) cells have been identified to maintain the immune homeostasis in terms of suppressing the activated immune components. According to this discovery, it is suggested that treating autoimmune patients by supplementing Treg cells would be a good choice. However, due to their natural scarcity, it is difficult to isolate a desired number of Treg for this therapeutical approach. Here, we report that by using stem cells, especially the induced pluripotent stem (iPS) cells, we are able to generate a significant amount of Treg cells for the autoimmune prevention and treatment. PMID:25173398

Lei, Fengyang; Haque, Rizwanul; Xiong, Xiaofang; Song, Jianxun

2014-01-01

201

Recurrence of autoimmunity in pancreas transplant patients: research update  

PubMed Central

SUMMARY Type 1 diabetes is an autoimmune disorder leading to loss of pancreatic ?-cells and insulin secretion, followed by insulin dependence. Islet and whole pancreas transplantation restore insulin secretion. Pancreas transplantation is often performed together with a kidney transplant in patients with end-stage renal disease. With improved immunosuppression, immunological failures of whole pancreas grafts have become less frequent and are usually categorized as chronic rejection. However, growing evidence indicates that chronic islet autoimmunity may eventually lead to recurrent diabetes, despite immunosuppression to prevent rejection. Thus, islet autoimmunity should be included in the diagnostic work-up of graft failure and ideally should be routinely assessed pretransplant and on follow-up in Type 1 diabetes recipients of pancreas and islet cell transplants. There is a need to develop new treatment regimens that can control autoimmunity, as this may not be effectively suppressed by conventional immunosuppression. PMID:21927622

Pugliese, Alberto; Reijonen, Helena K; Nepom, Jerry; Burke, George W

2011-01-01

202

Diagnostic criteria of autoimmune hepatitis.  

PubMed

Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disorder characterised by female preponderance, elevated transaminase and immunoglobulin G levels, seropositivity for autoantibodies and interface hepatitis. Presentation is highly variable, therefore AIH should be considered during the diagnostic workup of any increase in liver enzyme levels. A set of inclusion and exclusion criteria for the diagnosis of AIH have been established by the International Autoimmune Hepatitis Group (IAIHG). There are two main types of AIH: type 1, positive for anti-nuclear (ANA) and/or anti-smooth muscle antibodies (SMAs) and type 2, defined by the presence of anti-liver kidney microsomal antibody type 1 (LKM-1) and/or anti-liver cytosol type 1 (LC-1) autoantibodies. The central role of autoantibodies in the diagnosis of AIH has led the IAIHG to produce a consensus statement detailing appropriate and effective methods for their detection. Autoantibodies should be tested by indirect immunofluorescence at an initial dilution of 1/40 in adults and 1/10 in children on a freshly prepared rodent substrate that includes kidney, liver and stomach sections to allow for the simultaneous detection of all reactivities relevant to AIH. Anti-LKM-1 is often confused with anti-mitochondrial antibody (AMA) if rodent kidney is used as the sole immunofluorescence substrate. The identification of the molecular targets of anti-LKM-1 and AMA has led to the establishment of immuno-assays based on the use of the recombinant or purified autoantigens. Perinuclear anti-nuclear neutrophil antibody (p-ANNA) is an additional marker of AIH-1; anti soluble liver antigen (SLA) antibodies are specific for autoimmune liver disease, can be present in AIH-1 and AIH-2 and are associated with a more severe clinical course. Anti-SLA are detectable by ELISA or radio-immuno-assays, but not by immunofluorescence. AIH is exquisitely responsive to immunosuppressive treatment, which should be instituted promptly to prevent rapid deterioration and promote remission and long-term survival. PMID:24418295

Liberal, Rodrigo; Grant, Charlotte R; Longhi, Maria Serena; Mieli-Vergani, Giorgina; Vergani, Diego

2014-01-01

203

Cutaneous Manifestations as Presenting Sign of Autoimmune Lymphoproliferative Syndrome in Childhood  

Microsoft Academic Search

Autoimmune lymphoproliferative syndrome is a disorder due to a defect of lymphocyte apoptosis, whose clinical manifestations consist of hyperplasia of lymphoid tissues and autoimmune diseases. We report on a 26-month-old child who presented with frequent eruptions of weals and angioedema without any apparent triggering factor, who subsequently developed an erythematopapular rash with a histological pattern of a lymphoplasmacellular infiltrate. Familial

Luigi Auricchio; Laura Vitiello; Marsilio Adriani; Pasqualina Ferri; Annalisa Chiocchetti; Guido Pettinato; Luigi Racioppi; Luigi Maiuri; Umberto Dianzani; Claudio Pignata

2005-01-01

204

Human T-Cell Clones from Autoimmune Thyroid Glands: Specific Recognition of Autologous Thyroid Cells  

Microsoft Academic Search

The thyroid glands of patients with autoimmune diseases such as Graves' disease and certain forms of goiter contain infiltrating activated T lymphocytes and, unlike cells of normal glands, the epithelial follicular cells strongly express histocompatability antigens of the HLA-DR type. In a study of such autoimmune disorders, the infiltrating T cells from the thyroid glands of two patients with Graves'

Marco Londei; G. Franco Bottazzo; Marc Feldmann

1985-01-01

205

Autoimmune thyroiditis presenting as interstitial granulomatous dermatitis.  

PubMed

A 54-year-old female presented with recurrent, widespread, erythematous, painful plaques, over a 3-month period. Skin biopsy was compatible with interstitial granulomatous dermatitis. Additional investigation revealed hypothyroidism and positive anti-thyroid antibodies. Normalization of thyroid function and high-potency topical corticosteroids provided only transitory improvement of the dermatosis. Interstitial granulomatous dermatitis is a histologic inflammatory reaction, with variable cutaneous expression. It has been reported in association with several drugs, lymphoproliferative diseases and autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus and vasculitis, but association with autoimmune thyroiditis is rare. Optimal therapy for this condition is yet to be established, but topical corticosteroids have been a mainstay of treatment. In most cases, this disease is characterized by flares and remissions. PMID:23044569

Antunes, Joana; Pacheco, David; Travassos, Ana Rita; Soares-Almeida, Luís Miguel; Filipe, Paulo; Sacramento-Marques, Manuel

2012-01-01

206

Immunotherapeutic strategies in autoimmune uveitis.  

PubMed

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

2014-09-01

207

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

208

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

209

Targeting Dendritic Cell Function during Systemic Autoimmunity to Restore Tolerance  

PubMed Central

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

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

2014-01-01

210

Targeting dendritic cell function during systemic autoimmunity to restore tolerance.  

PubMed

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

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

2014-01-01

211

High Prevalence of Antinuclear Antibodies in Children with Thyroid Autoimmunity  

PubMed Central

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

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

2014-01-01

212

The Immunopathogenesis of Chronic Autoimmune Thyroiditis One Century after Hashimoto  

PubMed Central

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

Weetman, Anthony P

2013-01-01

213

Acute Hemorrhagic Leukoencephalitis Associated With Autoimmune Myopathy  

PubMed Central

Introduction Acute hemorrhagic leukoencephalitis is a rare acute inflammatory myelinopathy of central nervous system with high mortality. We report a case of an unusual presentation of acute hemorrhagic leukoencephalitis with autoimmune myopathy and a complete recovery with steroids and plasmapheresis. Methods A 24-year-old female admitted with generalized seizure, lethargy, but no focal neurological signs. Head scans revealed right frontal hypodensity with loss of basal cisterns, mild transfalcine shift to the left, a mass lesion with abnormal signal and multiple small hemorrhages. Biopsy pathology showed white matter demyelinating lesions with necrotizing destruction of small vessels and acute inflammation. EMG was consistent with demyelinating diffuse polyneuropathy and myopathy. Pathology of muscle showed myopathic changes suggestive of autoimmune myopathy. Results Patient was initially treated with Dexamethasone, Mannitol, Keppra, Antibiotics and Acyclovir. Later when she developed diffuse polyneuropathy and myopathy, she was given plasmapheresis. The patient responded to the treatment and made a full recovery. Conclusion Acute hemorrhagic leukoencephalitis is a rare and usually fatal disorder. The etiology of AHLE remains clear; cross-reactivity between human myelin antigens and viral or bacterial antigens is thought to initiate an immune process causing demyelination. Usually the autoimmune process targets CNS myelin and spares the peripheral; however, in this case there was diffuse involvement of central and peripheral myelin and muscle.

2014-01-01

214

Referral Centres for Systemic Autoimmune Diseases, Fondazione  

E-print Network

S-18 1 Referral Centres for Systemic Autoimmune Diseases, Fondazione IRCCS Ospedale Maggiore correspondence to: Dr Lorenzo Beretta, Referral Centres for Systemic Autoimmune Diseases, Fondazione IRCCS sclerosis (SSc) is a complex autoimmune disease with multiorgan involvement that results in significant

Chawla, Nitesh V.

215

Treatment of autoimmune hemolytic anemias.  

PubMed

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

2014-10-01

216

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 Herran-Arita, Alberto K.; Mignot, Emmanuel

2013-01-01

217

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

218

Fueling Autoimmunity: Type I Interferon in Autoimmune Diseases  

PubMed Central

Summary In recent years, active research using genomic, cellular and animal modeling approaches has revealed the fundamental forces driving the development of autoimmune diseases. Type I IFN (IFN) imprints unique molecular signatures in a list of autoimmune diseases. IFN is induced by diverse nucleic acid-containing complexes, which trigger innate immune activation of plasmacytoid dendritic cells (pDCs). IFN primes, activates or differentiates various leukocyte populations to promote autoimmunity. Accordingly, IFN signaling is essential for the initiation and/or progression of lupus in several experimental models. However, the heterogeneous nature of SLE requires better characterization on how IFN pathways are activated and subsequently promote the advancement of autoimmune diseases. Given the central role of type I IFN, various strategies are devised to target these cytokines or related pathways to curtail the progression of autoimmune diseases. PMID:23445195

Di Domizio, Jeremy; Cao, Wei

2013-01-01

219

Autoimmune Liver Diseases in Canterbury, New Zealand.  

E-print Network

??Autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are progressive autoimmune liver diseases (AiLD) that can lead to liver cirrhosis, hepatic… (more)

Ngu, Jing Hieng

2013-01-01

220

Immunoregulatory T cells in autoimmunity  

Microsoft Academic Search

The aim of this work was to discuss the current knowledge concerning regulatory T cells in the pathogenesis of autoimmune diseases. CD4+ T cells that constitutively express CD25 exhibit powerful suppressive properties. Such cells have been denominated regulatory T cells (TR). Alterations in TR cells are known to cause organ-specific autoimmune disease in animal models. These cells are anergic when

Jose C Crispin; Maria Ines Vargas; Jorge Alcocer-Varela

2004-01-01

221

Environmental Triggers of Autoimmune Thyroiditis  

PubMed Central

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

Burek, C. Lynne; Talor, Monica V.

2009-01-01

222

Immune Checkpoints in CNS Autoimmunity  

PubMed Central

Summary A number of autoimmune diseases, including multiple sclerosis, are mediated by self-reactive T cells that have escaped the deletional mechanisms of central tolerance. Usually, these T cells are kept at bay through peripheral tolerance mechanisms including regulation through coinhibitory receptors and suppression by regulatory T cells (Tregs). However, if these mechanisms fail, self-reactive T cells are activated and autoimmune responses ensue. This review outlines how the coinhibitory receptors CTLA-4, PD-1, Tim-3 and TIGIT act at different checkpoints to inhibit autoreactive T cells and suppress the development of CNS autoimmunity. Loss of each of these receptors predisposes to autoimmunity, indicating a non-redundant role in maintaining peripheral tolerance. At the same time, their functional patterns seem to overlap to a large degree. We therefore propose that only the concerted action of a combination of inhibitory receptors is able to maintain peripheral tolerance and prevent autoimmunity. PMID:22725958

Joller, Nicole; Peters, Anneli; Anderson, Ana C.; Kuchroo, Vijay K.

2013-01-01

223

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

224

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

2014-04-16

225

Autoimmunity in chronic lymphocytic leukaemia.  

PubMed Central

The prevalence of autoantibodies in B cell chronic lymphocytic leukaemia (B-CLL) was investigated. A lower prevalence of autoimmune haemolytic anaemia than that found in other series was found: large numbers of non-progressive stage A disease cases were included, in which the prevalence of autoimmune haemolytic anaemia is low. Non-haematological autoantibodies were no commoner than in age matched controls. Whatever explanation is offered for autoimmune phenomena in B-CLL it must take account of the fact that those phenomena are virtually confined to autoantibodies against the formed elements of the blood. PMID:3488334

Hamblin, T J; Oscier, D G; Young, B J

1986-01-01

226

"Thyroid Disorders" Deaf Health Talks  

E-print Network

"Thyroid Disorders" Deaf Health Talks Rochester Recreation Club for the Deaf October 21, 2010 #12 do for us? What are common types of thyroid disorders? What are causes for thyroid disorders? How can cause of hypothyroidism ("slow thyroid") in the world? A. Infection B. Autoimmune- body attacks itself

Goldman, Steven A.

227

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

228

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

PubMed

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

Cunningham, Madeleine W

2014-01-01

229

P-Glycoprotein and Drug Resistance in Systemic Autoimmune Diseases  

PubMed Central

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

Picchianti-Diamanti, Andrea; Rosado, Maria Manuela; Scarsella, Marco; Lagana, Bruno; D'Amelio, Raffaele

2014-01-01

230

Neurobehavioral alterations in autoimmune mice  

Microsoft Academic Search

Inbred MRL, NZB and BXSB strains of mice spontaneously develop a systemic, lupus-like autoimmune disease. The progress of autoirnmunity is accompanied with a cascade of behavioral changes, most consistently observed in tasks reflective of emotional reactivity and the two-way avoidance learning task. Given the possibility that behavioral alterations may reflect a detrimental consequence of autoimmune-inflammatory processes and\\/or an adaptive response

Boris Šaki?; Henry Szechtivian; Judah A Denburg

1997-01-01

231

Autoimmunity in Common Variable Immunodeficiency  

Microsoft Academic Search

Background  Autoimmunity has been increasingly recognized as a major issue in patients with common variable immunodeficiency (CVID), the\\u000a most common symptomatic primary immunodeficiency in adulthood. Different authors report high prevalences of autoimmune diseases\\u000a in CVID, and several mechanisms have been proposed to explain this apparent paradox. Genetic predisposition, under current\\u000a surveillance, innate and adaptive immunity deficiencies leading to persistent\\/recurrent infections, variable

Susana Lopes-da-Silva; Luiz Vicente Rizzo

2008-01-01

232

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

233

Anti-inflammatory effects of bromocriptine in a patient with autoimmune polyglandular syndrome type 2.  

PubMed

Excessive prolactin release and/or receptor action may be implicated in the pathogenesis of many autoimmune disorders. We report here a case of a woman who developed Graves' disease and subclinical autoimmune adrenal failure, and was diagnosed as having autoimmune polyglandular syndrome type 2. Because of coexisting microprolactinoma she was treated with bromocriptine for 24 months. This treatment resulted in a normalization of thyroid and adrenal function tests (with the exception of 21-hydroxylase antibodies) and reduced monocyte cytokine release. Our study indicates that bromocriptine and probably also the remaining prolactin-lowering agents produce anti-inflammatory effects and may prevent or delay the progression of autoimmune disorders of endocrine glands. PMID:24977964

Krysiak, Robert; Samborek, Malgorzata; Stojko, Rafal

2014-01-01

234

SOCS, Inflammation, and Autoimmunity  

PubMed Central

Cytokines play essential roles in innate and adaptive immunity. However, excess cytokines or dysregulation of cytokine signaling will cause a variety of diseases, including allergies, autoimmune diseases, inflammation, and cancer. Most cytokines utilize the so-called Janus kinase–signal transducers and activators of transcription pathway. This pathway is negatively regulated by various mechanisms including suppressors of cytokine signaling (SOCS) proteins. SOCS proteins bind to JAK or cytokine receptors, thereby suppressing further signaling events. Especially, suppressor of cytokine signaling-1 (SOCS1) and SOCS3 are strong inhibitors of JAKs, because these two contain kinase inhibitory region at the N-terminus. Studies using conditional knockout mice have shown that SOCS proteins are key physiological as well as pathological regulators of immune homeostasis. Recent studies have also demonstrated that SOCS1 and SOCS3 are important regulators of helper T cell differentiation and functions. This review focuses on the roles of SOCS1 and SOCS3 in T cell mediated inflammatory diseases. PMID:22566904

Yoshimura, Akihiko; Suzuki, Mayu; Sakaguchi, Ryota; Hanada, Toshikatsu; Yasukawa, Hideo

2011-01-01

235

Somatic Mutagenesis in Autoimmunity  

PubMed Central

Our laboratory investigates systemic autoimmune disease in the context of mouse models of systemic lupus erythematosus (SLE). SLE is associated with high titers of serum autoantibodies of the IgG class that are predominantly directed against nuclear antigens, with pathological manifestations that are considered by many to be characteristic of an immune-complex mediated disease. In this review, we focus on the known and potential roles of somatic mutagenesis in SLE. We will argue that antinuclear antibodies (ANA) arise predominantly from nonautoreactive B cells that are transformed into autoreactive cells by the process of somatic hypermutation (SHM), which is normally associated with affinity maturation during the germinal center reaction. We will also discuss the role of SHM in creating antigenic peptides in the V region of the B cell receptor (BCR) and its potential to open an avenue of unregulated T cell help to autoreactive B cells. Finally, we will end this review with new experimental evidence suggesting that spontaneous somatic mutagenesis of genes that regulate B cell survival and activation is a rate-limiting causative factor in the development of ANA. PMID:23249093

Detanico, Thiago; St Clair, James B.; Aviszus, Katja; Kirchenbaum, Greg; Guo, Wenzhong; Wysocki, Lawrence J

2013-01-01

236

Heparanase and Autoimmune Diabetes  

PubMed Central

Heparanase (Hpse) is the only known mammalian endo-?-d-glucuronidase that degrades the glycosaminoglycan heparan sulfate (HS), found attached to the core proteins of heparan sulfate proteoglycans (HSPGs). Hpse plays a homeostatic role in regulating the turnover of cell-associated HS and also degrades extracellular HS in basement membranes (BMs) and the extracellular matrix (ECM), where HSPGs function as a barrier to cell migration. Secreted Hpse is harnessed by leukocytes to facilitate their migration from the blood to sites of inflammation. In the non-obese diabetic (NOD) model of autoimmune Type 1 diabetes (T1D), Hpse is also used by insulitis leukocytes to solubilize the islet BM to enable intra-islet entry of leukocytes and to degrade intracellular HS, an essential component for the survival of insulin-producing islet beta cells. Treatment of pre-diabetic adult NOD mice with the Hpse inhibitor PI-88 significantly reduced the incidence of T1D by ~50% and preserved islet HS. Hpse therefore acts as a novel immune effector mechanism in T1D. Our studies have identified T1D as a Hpse-dependent disease and Hpse inhibitors as novel therapeutics for preventing T1D progression and possibly the development of T1D vascular complications. PMID:24421779

Simeonovic, Charmaine J.; Ziolkowski, Andrew F.; Wu, Zuopeng; Choong, Fui Jiun; Freeman, Craig; Parish, Christopher R.

2013-01-01

237

Progesterone and Autoimmune Disease  

PubMed Central

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

Hughes, Grant C.

2011-01-01

238

Coeliac disease in 2013: new insights in dietary-gluten-induced autoimmunity.  

PubMed

Coeliac disease comprises intolerance against dietary wheat, rye and barley gluten and is one of the most common food-related life-long disorders in Western countries. In 2013, new knowledge of the clinical diversity of coeliac disease and further details about the autoimmune aspects of this disorder have emerged. PMID:24322900

Kaukinen, Katri; Mäki, Markku

2014-02-01

239

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

240

Co-inherited mutations of Fas and caspase-10 in development of the autoimmune lymphoproliferative syndrome  

Microsoft Academic Search

BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder characterized by defective function of Fas, autoimmune manifestations that predominantly involve blood cells, polyclonal accumulation of lymphocytes in the spleen and lymph nodes with lymphoadenomegaly and\\/or splenomegaly, and expansion of TCR??+ CD4\\/CD8 double-negative (DN) T cells in the peripheral blood. Most frequently, it is due to Fas gene mutations, causing

Elisa Cerutti; Maria F Campagnoli; Massimo Ferretti; Emanuela Garelli; Nicoletta Crescenzio; Angelo Rosolen; Annalisa Chiocchetti; Michael J Lenardo; Ugo Ramenghi; Umberto Dianzani

2007-01-01

241

Frequency and Significance of Anti-gliadin and Anti-endomysial Antibodies in Autoimmune Hepatitis  

Microsoft Academic Search

Celiac disease has been associated withautoimmune disorders, but its frequency in autoimmunehepatitis is unknown. Sera from 157 patients with type1 autoimmune hepatitis, 24 patients with type 2autoimmune hepatitis, 62 patients with primary biliarycirrhosis, 30 patients with chronic hepatitis B, and 80patients with chronic hepatitis C were tested forimmunoglobulin A anti-endomysial antibodies by indirect immunofluorescence and immunoglobulin A and Gantibodies to

U. Volta; L. De Franceschi; N. Molinaro; F. Cassani; L. Muratori; M. Lenzi; F. B. Bianchi; A. J. Czaja

1998-01-01

242

The Role of NK Cells in the Autoimmune Thyroid Disease-associated Pregnancy Loss  

Microsoft Academic Search

Pregnancy loss is a frequent event. Autoimmune thyroid disorders and altered natural killer (NK) cell functions are two distinct\\u000a risk factors, which independently could induce adverse pregnancy outcome. Thyroid autoimmunity has been an object of increased\\u000a attention by investigators in the context of pregnancy loss. Peripheral NK cells and uNK cells comprise distinct cell populations\\u000a in terms of phenotype and

Emiliana Konova

2010-01-01

243

Increased sleep fragmentation in experimental autoimmune encephalomyelitis.  

PubMed

Sleep disturbance in patients with multiple sclerosis is prevalent and has multifactorial causes. In mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, we determined the dynamic changes of sleep architecture and the interactions between sleep changes and EAE symptoms. The changes of sleep patterns were mainly reflected by altered sleep stage distribution and increased sleep fragmentation. Increased waking and decreased non-rapid eye movement sleep occurred after EAE onset and persisted through the symptomatic phase. There also was increased sleep state transition, indicating a reduction of sleep cohesiveness. Furthermore, the extent of sleep fragmentation correlated with the severity of disease. This is the first study of sleep characteristics in EAE mice demarcating specific changes related to the autoimmune disorder without confounding factors such as psychosocial impact and treatment effects. The reduction of sleep efficiency and cohesiveness supports the notion that enhancing sleep might facilitate the recovery of mice from EAE, pertinent to the multimodality treatment of multiple sclerosis. PMID:24566387

He, Junyun; Wang, Yuping; Kastin, Abba J; Pan, Weihong

2014-05-01

244

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

245

GENETIC AND EPIGENETIC MECHANISMS IN THYROID AUTOIMMUNITY  

PubMed Central

Autoimmune thyroid diseases (AITD), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are amongst the commonest autoimmune disorders, affecting approximately 5% of the population. Epidemiological data support strong genetic influences on the development of AITD. Since the identification of HLA-DR3 as a major AITD susceptibility gene, there have been significant advances made in our understanding of the genetic mechanisms leading to AITD. We have shown that an amino acid substitution of alanine or glutamine with arginine at position 74 in the HLA-DR peptide-binding pocket is a critical factor in the development of AITD, and we are continuing to dissect these mechanisms at the molecular level. In addition to the MHC class II genes, there are now several other confirmed gene-loci associated with AITD, including immune-regulatory (CD40, CTLA-4, PTPN22, FOXP3, and CD25) and thyroid-specific genes (thyroglobulin and TSHR). Mechanistically, it is postulated that susceptibility genes interact with certain environmental triggers to induce AITD through epigenetic effects. In this review, we summarize some of the recent advances made in our lab dissecting the genetic-epigenetic interactions underlying AITD. As shown in our recent studies, epigenetic modifications offer an attractive mechanistic possibility which can provide further insight into the etiology of AITD. PMID:22457094

Hasham, Alia; Tomer, Yaron

2013-01-01

246

Genetic and epigenetic mechanisms in thyroid autoimmunity.  

PubMed

Autoimmune thyroid diseases (AITD), including Graves' disease and Hashimoto's thyroiditis, are among the commonest autoimmune disorders, affecting approximately 5 % of the population. Epidemiological data support strong genetic influences on the development of AITD. Since the identification of HLA-DR3 as a major AITD susceptibility gene, there have been significant advances made in our understanding of the genetic mechanisms leading to AITD. We have shown that an amino acid substitution of alanine or glutamine with arginine at position 74 in the HLA-DR peptide binding pocket is a critical factor in the development of AITD, and we are continuing to dissect these mechanisms at the molecular level. In addition to the MHC class II genes, there are now several other confirmed gene loci associated with AITD, including immune-regulatory (CD40, CTLA-4, PTPN22, FOXP3, and CD25) and thyroid-specific genes (thyroglobulin and TSHR). Mechanistically, it is postulated that susceptibility genes interact with certain environmental triggers to induce AITD through epigenetic effects. In this review, we summarize some of the recent advances made in our laboratory dissecting the genetic-epigenetic interactions underlying AITD. As shown in our recent studies, epigenetic modifications offer an attractive mechanistic possibility that can provide further insight into the etiology of AITD. PMID:22457094

Hasham, Alia; Tomer, Yaron

2012-12-01

247

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

248

Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis: a descriptive study  

Microsoft Academic Search

Methods A total of 176 families (386 individuals and 1107 fi rst-degree relatives) were characterised for a history of other autoimmune disorders. Family-based or case-control analyses were done to assess the association of cytotoxic T-lymphocyte-antigen 4 (CTLA4) and protein tyrosine phosphatase (PTPN22) variants with susceptibility to multiple sclerosis. Findings 46 (26%) index cases reported at least one coexisting autoimmune disorder.

Lisa F Barcellos; Brinda B Kamdar; Patricia P Ramsay; Cari DeLoa; Robin R Lincoln; Stacy Caillier; Silke Schmidt; Jonathan L Haines; Margaret A Pericak-Vance; Jorge R Oksenberg; Stephen L Hauser

2006-01-01

249

Identification of masqueraders of autoimmune disease in the office.  

PubMed

There are several rheumatologic and autoimmune disorders that can masquerade as allergic disease. Identification of these conditions in an office setting can be a challenge for the practicing allergist-immunologist. These conditions include rheumatoid and juvenile arthritis, Sjogren's syndrome, systemic lupus erythematosus, Behcet's and antiphospholipid syndromes, systemic sclerosis, vasculitis, sarcoidosis, chronic fatigue syndrome, and fibromyalgia. The article will address these topics and include clinical uses of immunologic tests for diagnosis. PMID:14763244

Frieri, Marianne

2003-01-01

250

Drug-induced autoimmunity: experience of the French Pharmacovigilance system  

Microsoft Academic Search

Spontaneous reporting of suspected adverse drug reactions to a pharmacovigilance structure is a reasonable tool to detect new associations between drugs and a given toxic effect. An analysis of the French national database of pharmacovigilance was undertaken to evaluate how such a system is relevant to survey and\\/or detect drug-associated autoimmune disorders. Only 0.2% of reports were coded with terms

Thierry Vial; Brigitte Nicolas; Jacques Descotes

1997-01-01

251

Relevance of protein nitration in brain injury: a key pathophysiological mechanism in neurodegenerative, autoimmune, or inflammatory CNS diseases and stroke  

Microsoft Academic Search

Summary. This review has focused on the evidence for the involvement of nitrative oxidation in certain neurodegenerative disorders (Parkinson’s Disease, Alzheimer’s Disease, Amyotrophic Lateral Sclerosis), stroke, and inflammatory and autoimmune disorders (with particular attention devoted to multiple sclerosis). The relationship between protein peroxidation and pathological changes observed in the above disorders has been reported. Whereas many of the findings are

P. Sarchielli; F. Galli; Ar. Floridi; Al. Floridi; V. Gallai

2003-01-01

252

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

253

Autoimmune Thyroiditis Presenting as Palmoplantar Keratoderma  

PubMed Central

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, Claudia; Barata Feio, Ana

2010-01-01

254

Th17 Cells in Immunity and Autoimmunity  

PubMed Central

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

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

2013-01-01

255

Targeting apoptosis in autoimmune hepatitis.  

PubMed

Apoptosis is the predominant mechanism of liver cell death in autoimmune hepatitis, and interventions that can modulate this activity are emerging. The aim of this review was to describe the apoptotic mechanisms, possible aberrations, and opportunities for intervention in autoimmune hepatitis. Studies cited in PubMed from 1972 to 2014 for autoimmune hepatitis, apoptosis in liver disease, apoptosis mechanisms, and apoptosis treatment were examined. Apoptosis is overactive in autoimmune hepatitis, and the principal pathway of cell death is receptor mediated. Surface death receptors are activated by extrinsic factors including liver-infiltrating cytotoxic T cells and the cytokine milieu. The executioner caspases 3 and 7 cleave nuclear deoxyribonucleic acid, and the release of apoptotic bodies can stimulate inflammatory, immune, and fibrotic responses. Changes in mitochondrial membrane permeability can be initiated by caspase 8, and an intrinsic pathway of apoptosis can complement the extrinsic pathway. Defects in the apoptosis of activated effector cells can prolong their survival and sustain the immune response. Caspase inhibitors have been used in diverse experimental and human diseases to retard apoptosis. Oligonucleotides that inhibit the signaling of toll-like receptors can limit the presentation of auto-antigens, and inhibitors of apoptosis that extend the survival of effector cells can be blocked by antisense oligonucleotides. Mechanisms that enhance the clearance of apoptotic bodies and affect key signaling pathways are also feasible. Interventions that influence the survival of liver and effector cells by altering their apoptosis are candidates for study in autoimmune hepatitis. PMID:25038736

Czaja, Albert J

2014-12-01

256

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

257

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

PubMed Central

Background The significance of hypergammaglobulinemia as a marker of immune activation is unknown, as a differential diagnosis for hypergammaglobulinemia in children has not been adequately established. The goal of this study was to identify conditions associated with hypergammaglobulinemia in children, with the hypothesis that elevated immunoglobulin levels may precede or predict the development of autoimmune conditions. Methods We reviewed the medical records for all children with IgG level ?2000 mg/dL treated at a tertiary care children’s hospital from January 1, 2000 through December 31, 2009. We compared clinical and laboratory features of these patients, and developed an algorithm to predict the likelihood of underlying autoimmunity based on these characteristics. Results After excluding children who had received IVIG, a total of 442 patients with hypergammaglobulinemia were identified. Of these, nearly half had autoimmune conditions, most frequently systemic lupus erythematosus and lupus-related disorders. Autoimmune gastrointestinal disorders such as inflammatory bowel disease were also common. Infectious diseases were the next largest category of diseases, followed with much less frequency by malignant, drug-related, and other conditions. In comparison with non-autoimmune conditions, patients with autoimmune disease had higher IgG levels, lower white blood cell counts, lower hemoglobin values, and lower C-reactive protein (CRP) levels. Multivariable logistic regression confirmed that CRP (P?=?0.002), white blood cell count (P?autoimmune disease in patients with high IgG levels. Conclusions In a cohort of pediatric patients at a tertiary care children’s hospital, hypergammaglobulinemia was most commonly associated with autoimmune diseases. In female patients with hypergammaglobulinemia, the presence of leukopenia, anemia, and normal CRP was 95% predictive of underlying autoimmune disease. PMID:24180594

2013-01-01

258

RNAi Therapeutics in Autoimmune Disease  

PubMed Central

Since the discovery of RNA interference (RNAi), excitement has grown over its potential therapeutic uses. Targeting RNAi pathways provides a powerful tool to change biological processes post-transcriptionally in various health conditions such as cancer or autoimmune diseases. Optimum design of shRNA, siRNA, and miRNA enhances stability and specificity of RNAi-based approaches whereas it has to reduce or prevent undesirable immune responses or off-target effects. Recent advances in understanding pathogenesis of autoimmune diseases have allowed application of these tools in vitro as well as in vivo with some degree of success. Further research on the design and delivery of effectors of RNAi pathway and underlying molecular basis of RNAi would warrant practical use of RNAi-based therapeutics in human applications. This review will focus on the approaches used for current therapeutics and their applications in autoimmune diseases, including rheumatoid arthritis and Sjögren’s syndrome. PMID:24276020

Pauley, Kaleb M.; Cha, Seunghee

2013-01-01

259

Type 1 autoimmune pancreatitis  

PubMed Central

Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of regulatory T-cells are assumed to be involved in the underlying immune reaction. IgG4 antibodies have two unique biological functions, Fab-arm exchange and a rheumatoid factor-like activity, both of which may play immune-defensive roles. However, the exact role of IgG4 in this disease still remains to be clarified. It seems important to recognize this unique entity given that the disease is treatable with steroids. PMID:22151922

2011-01-01

260

In silico study of potential autoimmune threats from rotavirus infection.  

PubMed

Rotavirus, the major cause of infantile nonbacterial diarrhea, was found to be associated with development of diabetes-associated auto-antibodies. In our study we tried to find out further potential autoimmune threats of this virus using bioinformatics approach. We took rotaviral proteins to study similarity with Homo sapiens proteome and found most conserved structural protein VP6 matches at two regions with ryanodine receptor, an autoimmune target associated with myasthenia gravis. Myasthenia gravis, a chronic neurodegenerative autoimmune disorder with no typical known reason, is characterized by fluctuating muscle weakness which is typically enhanced during muscular effort. Affected patients generate auto antibodies against mainly acetyl choline receptor and sarcoplasmic reticulum calcium-release channel protein ryanodine receptor. Further, we observed that two regions which matched with ryanodine receptor remain conserved in all circulating rotaviral strains and showed significant antigenecity with respect to myasthenia gravis associated HLA haplotypes. Overall, our study detected rotaviral VP6 as a potential threat for myasthenia gravis and enlighten an area of virus associated autoimmune research. PMID:24929545

Sarkar, Tapati; Das, Sukhen; Nandy, Papiya; Bhowmick, Rahul; Nandy, Ashesh

2014-08-01

261

Therapy of Autoimmune Connective Tissue Diseases  

Microsoft Academic Search

\\u000a The autoimmune diseases can be divided into two basic categories: organ specific and systemic. Organ specific autoimmune disease can affect virtually any tissue of the body and is associated most often with evidence\\u000a of both T and B cell autoimmune responses directed against the cells of the affected organ. Examples of organ specific autoimmune\\u000a disease include multiple sclerosis, Type I

Timothy M. Wright; Dana P. Ascherman

262

Autoimmune manifestations in primary immune deficiencies  

Microsoft Academic Search

Autoimmune manifestations have long been perceived as paradoxical in patients with primary immune deficiencies (PID). However, a defect in the mechanisms of control of self-reactive B and T cells may favour these manifestations.Three PID are defined by the occurrence of autoimmune manifestations: APECED (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy), autoimmune lymphoproliferative syndrome (ALPS) and IPEX syndrome (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). In these

Guillaume Bussone; Luc Mouthon

2009-01-01

263

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

264

Invited Review Autoimmunity in Chagas heart disease  

E-print Network

Invited Review Autoimmunity in Chagas heart disease J.S. Leon, D.M. Engman* Northwestern University the genesis of autoimmunity in Chagas heart disease: (i) What mechanism(s) are potentially responsible for Parasitology Inc. Keywords: Myocarditis; Chagas heart disease Myosin; Autoimmunity 1. Introduction After

Engman, David M.

265

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

266

[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

267

Toward molecular pathogenesis of an autoimmune disease: Refined genetic mapping of autoimmune polyglandular disease type I (APECED)  

SciTech Connect

Autoimmune reactions encoupled to many human diseases are still only partially understood. Unravelling the molecular pathogenesis of inherited diseases with a strong autoimmune component in their clinical expression could help to dissect individual components in the molecular background of abnormal immune response. One such genetic disorder is autosomal recessive autoimmune polyglandular disease type I (PGD I), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, MIM 240300). The disease is especially enriched in the genetically isolated population of Finland and we have assigned the APECED locus to human chromosome 21q22.3 in 14 Finnish families by linkage analyses. The best positional lod score of 6.49 was observed with marker D21S49. Based on the history of the Finns, the gene pool of this population clearly demonstrates the consequences of a founder effect and consequent isolation. In the Finnish population, we can take advantage of linkage disequilibrium and allelic association studies to more precisely define the critical DNA region for our disease gene of interest than would be possible by linkage analyses alone. We are now able to define the chromosomal region of interest between two flanking markers locating 1 cM apart. Linkage disequilibrium is observed with three of the markers used in the analyses and this suggests a distance of less than 500 kb to the disease locus, well approachable with molecular cloning techniques. Overlapping YAC and cosmid clones spanning our region of interest will facilitate the cloning of APECED gene in the near future.

Aaltonen, J.; Bjoerses, P.; Peltonen, L. [National Public Health Institute, Helsinki (Finland)] [and others

1994-09-01

268

Rat Models of Autoimmune Uveitis  

Microsoft Academic Search

Experimental autoimmune uveitis (EAU) in Lewis rats is a well-established model for human uveitis. During the last years we used this model to demonstrate extraocular induction of uveitis by antigenic mimicry of environmental antigens with retinal autoantigen and investigated the migration and intraocular reactivation of autoreactive green fluorescent protein (GFP)+ T cells. We could also elaborate several differences between EAU

Gerhild Wildner; Maria Diedrichs-Möhring; Stephan R. Thurau

2008-01-01

269

Cytokine inhibitors in autoimmune disease  

Microsoft Academic Search

The cytokine network participates in the modulation of the immune system. Furthermore, the formation of the cytokine-receptor complex, as well as the transcription, translation, secretion, or degradation of cytokines interfere with the functions of cytokines. Cytokine inhibitors include antagonists, soluble receptors, cytokine-binding proteins, and cytokines that block other cytokines. In autoimmune diseases, an abnormal production of proinflammatory cytokines, or a

Ana Luisa Weckmann; Jorge Alcocer-Varela

1996-01-01

270

Historical reflections on autoimmune hepatitis  

PubMed Central

Autoimmune hepatitis (AIH), initially known as chronic active or active chronic hepatitis (and by various other names), first came under clinical notice in the late 1940s. However, quite likely, chronic active hepatitis (CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver. An earlier (and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E. cell test positivity and emphasized accompanying multisystem features and immunological aberrations. Young women featured prominently in early descriptions of CAH. AIH was first applied in 1965 as a descriptive term. Disease-characteristic autoantibodies were defined from the early 1960s, notably antinuclear antibody (ANA), smooth muscle antibody (SMA) and liver-kidney microsomal (LKM) antibody. These are still widely used diagnostically but their relationship to pathogenesis is still not evident. A liver and disease specific autoantigen has long been searched for but unsuccessfully. Prolonged immunosuppressive therapy with prednisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today. AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the “ancestral” B8, DR3 haplotype, and also with DR4. Looking forwards, AIH is one of the several enigmatic autoimmune diseases that, despite being (relatively) organ specific, are marked by autoimmune reactivities with non-organ-specific autoantigens. New paradigms are needed to explain the occurrence, expressions and pathogenesis of such diseases. PMID:18528926

Mackay, Ian R

2008-01-01

271

Mast cells in autoimmune disease  

Microsoft Academic Search

Mast cells are known to be the primary responders in allergic reactions, orchestrating strong responses to minute amounts of allergens. Several recent observations indicate that they may also have a key role in coordinating the early phases of autoimmune diseases, particularly those involving auto-antibodies.

Christophe Benoist; Diane Mathis

2002-01-01

272

Th17 Cells in Autoimmune and Infectious Diseases  

PubMed Central

The view of CD4 T-cell-mediated immunity as a balance between distinct lineages of Th1 and Th2 cells has changed dramatically. Identification of the IL-17 family of cytokines and of the fact that IL-23 mediates the expansion of IL-17-producing T cells uncovered a new subset of Th cells designated Th17 cells, which have emerged as a third independent T-cell subset that may play an essential role in protection against certain extracellular pathogens. Moreover, Th17 cells have been extensively analyzed because of their strong association with inflammatory disorders and autoimmune diseases. Also, they appear to be critical for controlling these disorders. Similar to Th1 and Th2 cells, Th17 cells require specific cytokines and transcription factors for their differentiation. Th17 cells have been characterized as one of the major pathogenic Th cell populations underlying the development of many autoimmune diseases, and they are enhanced and stabilized by IL-23. The characteristics of Th17 cells, cytokines, and their sources, as well as their role in infectious and autoimmune diseases, are discussed in this review. PMID:25152827

Zambrano-Zaragoza, Jose Francisco; Romo-Martinez, Enrique Jhonatan; Duran-Avelar, Ma. de Jesus; Garcia-Magallanes, Noemi; Vibanco-Perez, Norberto

2014-01-01

273

The role of infections in autoimmune disease  

PubMed Central

Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious pathogens) are thought to play a major role in the development of autoimmune diseases. In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity. PMID:19076824

Ercolini, A M; Miller, S D

2009-01-01

274

Experimental autoimmune encephalomyelitis repressed by microglial paralysis.  

PubMed

Although microglial activation occurs in inflammatory, degenerative and neoplastic central nervous system (CNS) disorders, its role in pathogenesis is unclear. We studied this question by generating CD11b-HSVTK transgenic mice, which express herpes simplex thymidine kinase in macrophages and microglia. Ganciclovir treatment of organotypic brain slice cultures derived from CD11b-HSVTK mice abolished microglial release of nitrite, proinflammatory cytokines and chemokines. Systemic ganciclovir administration to CD11b-HSVTK mice elicited hematopoietic toxicity, which was prevented by transfer of wild-type bone marrow. In bone marrow chimeras, ganciclovir blocked microglial activation in the facial nucleus upon axotomy and repressed the development of experimental autoimmune encephalomyelitis. We conclude that microglial paralysis inhibits the development and maintenance of inflammatory CNS lesions. The microglial compartment thus provides a potential therapeutic target in inflammatory CNS disorders. These results validate CD11b-HSVTK mice as a tool to study the impact of microglial activation on CNS diseases in vivo. PMID:15665833

Heppner, Frank L; Greter, Melanie; Marino, Denis; Falsig, Jeppe; Raivich, Gennadij; Hövelmeyer, Nadine; Waisman, Ari; Rülicke, Thomas; Prinz, Marco; Priller, Josef; Becher, Burkhard; Aguzzi, Adriano

2005-02-01

275

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

276

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

277

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

278

From single nucleotide polymorphisms to constant immunosuppression: mesenchymal stem cell therapy for autoimmune diseases.  

PubMed

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

Chinnadurai, Raghavan; Waller, Edmund K; Galipeau, Jacques; Nooka, Ajay K

2013-01-01

279

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

280

Animal models of autoimmune neuropathy.  

PubMed

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

281

Autoimmune diseases and reproductive aging  

PubMed Central

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

Bove, Riley

2013-01-01

282

Autoimmunity in common variable immunodeficiency  

Microsoft Academic Search

Common variable immunodeficiency (CVID) is the most common clinically significant primary immune defect. Although the hallmark\\u000a of CVID is hypogammaglobulinemia, the intrinsic dysregulation of the immune system leads to defective T-cell activation and\\u000a proliferation, as well as dendritic cell and cytokine defects. Although 70% to 80% of patients have had recurrent sinopulmonary\\u000a infections, autoimmunity and inflammatory complications are also common.

Shradha Agarwal; Charlotte Cunningham-Rundles

2009-01-01

283

Schizophrenia: prenatal influenza and autoimmunity.  

PubMed

The schizophrenic syndrome may represent a stereotyped response by the developing brain to various insults, including micro-organisms. We review studies that have examined the association between schizophrenia and infectious agents, and examine the current evidence for the hypothesis that exposure to influenza during fetal life increases the risk of later schizophrenia. A prenatal autoimmune basis for some cases of schizophrenia is proposed. PMID:8251151

Wright, P; Murray, R M

1993-10-01

284

Characterizing T-Cell Autoimmunity  

Microsoft Academic Search

\\u000a Immunological mechanisms which precipitate autoimmune diabetes involve the influence of a genetic footprint on the phenotype\\u000a of the T-cell response to self-antigens, and on development of pathological outcomes in immune responses resulting in T1D.\\u000a For one of the human diabetes antigens, proinsulin, recent findings allow the emergence of a model in which elements of genetically\\u000a biased T-cell development and peptide

Ivana Durinovic-Belló; Gerald T. Nepom

285

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

PubMed Central

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

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

2013-01-01

286

Pancreatic Tuberculosis or Autoimmune Pancreatitis  

PubMed Central

Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis. PMID:24839445

Saif, Muhammad Wasif

2014-01-01

287

The Autoimmune Model of Schizophrenia  

PubMed Central

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

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

2012-01-01

288

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

289

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

290

Immuno-neuro-endocrine networks: A study on the inflammatory state of circulating monocytes and CD4+ T cells in psychiatric and endocrine autoimmune disease  

Microsoft Academic Search

This thesis deals with immune aspects of bipolar disorder, schizophrenia, autoimmune\\u000athyroid disease and type 1 diabetes mellitus and therefore we give a short introduction to\\u000aeach disease.

R. C. Drexhage

2011-01-01

291

[The role of hereditary and environmental factors in autoimmune thyroid diseases].  

PubMed

Autoimmune thyroid diseases are the most common organ-specific autoimmune disorders affecting 5% to 10% of the population in Western countries. The clinical presentation varies from hyperthyroidism in Graves' disease to hypothyroidism in Hashimoto's thyroiditis. While the exact etiology of thyroid autoimmunity is not known, the interaction between genetic susceptibility and environmental factors appears to be of fundamental importance to initiate the process of thyroid autoimmunity. The identified autoimmune thyroid disease susceptibility genes include immune-modulating genes, such as the major histocompatibility complex, and thyroid-specific genes, including TSH receptor, thyroglobulin and thyroid peroxidase. The majority of the anti-TSH-receptor antibodies have a stimulating capacity and are responsible for hyperthyroidism. The anti-thyroglobulin- and anti-thyroid peroxidase antibodies belonging to the catalytic type of antibodies destroy the thyrocytes resulting in hypothyroidism. The appearance of anti-thyroid peroxidase antibodies precedes the induction of thyroiditis and the manifestation of hypothyroidism. The molecular analysis of thyroglobulin gene polymorphism is important in the mechanism of autoimmune thyroiditis. The autoantigen presentation by major histocompatibility complex molecules is a key point of the autoimmune mechanism. It has been shown that a HLA-DR variant containing arginine at position 74 of the DR?1 chain confers a strong genetic susceptibility to autoimmune thyroid diseases, Graves' disease and Hashimoto's thyroiditis, while glutamine at position DR?1-74 is protective. Human thyroglobulin 2098 peptide represents a strong and specific DR?1-Arg74 binder, while a non-binding control peptide, thyroglobulin 2766 fails to induce this response. Moreover, thyroglobulin 2098 stimulated T-cells from individuals who were positive for thyroglobulin antibodies, demonstrating that thyroglobulin 2098 is an immunogenic peptide capable of being presented in vivo and activating T-cells in autoimmune thyroid diseases. Taken together these findings suggest that thyroglobulin 2098, a strong and specific binder to the disease-associated HLA-DR?1-Arg74, is a major human T-cell epitope and it participates in the pathomechanism of the autoimmune thyroid disease. The exact nature of the role of environmental factors in the autoimmune thyroid disease is still not well known, but the importance of several factors such as iodine, drugs and infections has been reported. Further knowledge of the precise mechanisms of interaction between environmental factors and genes in inducing thyroid autoimmunity could result in the development of new strategies for diagnosis, prevention and treatment. PMID:22735372

Balázs, Csaba

2012-07-01

292

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

Microsoft Academic Search

An increased prevalence of autoimmune diseases in family members of children with autism spectrum disorders (ASD) has been\\u000a previously reported. ASD is also a common problem co-occurring in children with fragile X syndrome (FXS). Why ASD occurs in\\u000a some individuals with FXS, but not all, is largely unknown. Furthermore, in premutation carrier mothers, there is an increased\\u000a risk for autoimmune

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

2010-01-01

293

Understanding the pathogenesis of autoimmune hepatitis  

Microsoft Academic Search

OBJECTIVES:The aim of this study was to review the pathogenic mechanisms of autoimmune hepatitis, identify gaps in knowledge, and focus future investigative efforts.METHODS:The study was based on a review of all relevant articles on the mechanisms of autoimmunity in autoimmune liver disease from 1980 to 2000, extraction of pertinent concepts from the medical literature; and integration of evolving paradigms of

Albert J. Czaja

2001-01-01

294

Research paper Mineralocorticoid receptor mediates glucocorticoid treatment effects in the autoimmune mouse ear  

Microsoft Academic Search

The standard treatment for many hearing disorders is glucocorticoid therapy, although the cochlear mechanisms involved in steroid- responsive hearing loss are poorly understood. Cochlear dysfunction in autoimmune mice has recently been shown to be controlled with the mineralocorticoid aldosterone as effectively as with the glucocorticoid prednisolone. Because aldosterone regulates sodium, potas- sium, and other electrolyte homeostasis, this implied the restoration

Dennis R. Trune; J. Beth Kempton; Neil D. Gross

295

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

296

Common variable immune deficiency (CVID) presenting as an autoimmune disease: role of memory B cells  

Microsoft Academic Search

Common variable immunodeficiency (CVID) is a clinically heterogeneous disorder. Most often patients present with recurrent sinopulmonary infections, although it may present with autoimmune manifestations. Immune cytopenias, particularly thrombocytopenia and hemolytic anemia, are the most commonly observed. While the pathophysiology of CVID remains elusive, in many patients it may be due to an intrinsic B cell defect. Memory B cells (CD27+)

Bret R. Haymore; Cecilia P. Mikita; George C. Tsokos

2008-01-01

297

An evaluation of two new haemagglutination tests for the rapid diagnosis of autoimmune thyroid diseases.  

PubMed Central

Two haemagglutination tests using preserved turkey erythrocytes are described for the detection of thyroglobulin and microsomal antibodies, respectively. Comparative studies with the more traditional sheep cell techniques show good correlation of titres when testing sera from patients with autoimmune thyroid disorders. PMID:748386

Cayzer, I; Chalmers, S R; Doniach, D; Swana, G

1978-01-01

298

An evaluation of two new haemagglutination tests for the rapid diagnosis of autoimmune thyroid diseases.  

PubMed

Two haemagglutination tests using preserved turkey erythrocytes are described for the detection of thyroglobulin and microsomal antibodies, respectively. Comparative studies with the more traditional sheep cell techniques show good correlation of titres when testing sera from patients with autoimmune thyroid disorders. PMID:748386

Cayzer, I; Chalmers, S R; Doniach, D; Swana, G

1978-12-01

299

A Genomewide Screen in Multiplex Rheumatoid Arthritis Families Suggests Genetic Overlap with Other Autoimmune Diseases  

Microsoft Academic Search

† Rheumatoid arthritis (RA) is an autoimmune\\/inflammatory disorder with a complex genetic component. We report the first major genomewide screen of multiplex families with RA gathered in the United States. The North American Rheumatoid Arthritis Consortium, using well-defined clinical criteria, has collected 257 families containing 301 affected sibling pairs with RA. A genome screen for allele sharing was performed, using

Damini Jawaheer; Michael F. Seldin; Christopher I. Amos; Wei V. Chen; Russell Shigeta; Joanita Monteiro; Marlene Kern; Lindsey A. Criswell; Salvatore Albani; J. Lee Nelson; Daniel O. Clegg; Richard Pope; Harry W. Schroeder; S. Louis Bridges; David S. Pisetsky; Ryk Ward; Daniel L. Kastner; Ronald L. Wilder; Theodore Pincus; Leigh F. Callahan; Donald Flemming; Mark H. Wener; Peter K. Gregersen

2001-01-01

300

Aryl Hydrocarbon Receptor and Kynurenine: Recent Advances in Autoimmune Disease Research  

PubMed Central

Aryl hydrocarbon receptor (AHR) is thought to be a crucial factor in the regulation of immune responses. Many AHR-mediated immunoregulatory mechanisms have been discovered, and this knowledge may enhance our understanding of the molecular pathogenesis of autoimmune inflammatory syndromes such as collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental colitis. Recent findings have elucidated the critical link between AHR and indoleamine 2,3-dioxygenase (IDO) in the development of regulatory T cells and Th17 cells, which are key factors in a variety of human autoimmune diseases. Induction of IDO and IDO-mediated tryptophan catabolism, together with its downstream products such as kynurenine, is an important immunoregulatory mechanism underlying immunosuppression, tolerance, and immunity. Recent studies revealed that induction of IDO depends on AHR expression. This review summarizes the most current findings regarding the functions of AHR and IDO in immune cells as they relate to the pathogenesis of autoimmune diseases in response to various stimuli. We also discuss the potential link between AHR and IDO/tryptophan metabolites, and the involvement of several novel related factors (such as microRNA) in the development of autoimmune diseases. These novel factors represent potential therapeutic targets for the treatment of autoimmune disorders. PMID:25400638

Nguyen, Nam Trung; Nakahama, Taisuke; Le, Duc Hoang; Van Son, Le; Chu, Ha Hoang; Kishimoto, Tadamitsu

2014-01-01

301

Aryl hydrocarbon receptor and kynurenine: recent advances in autoimmune disease research.  

PubMed

Aryl hydrocarbon receptor (AHR) is thought to be a crucial factor in the regulation of immune responses. Many AHR-mediated immunoregulatory mechanisms have been discovered, and this knowledge may enhance our understanding of the molecular pathogenesis of autoimmune inflammatory syndromes such as collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental colitis. Recent findings have elucidated the critical link between AHR and indoleamine 2,3-dioxygenase (IDO) in the development of regulatory T cells and Th17 cells, which are key factors in a variety of human autoimmune diseases. Induction of IDO and IDO-mediated tryptophan catabolism, together with its downstream products such as kynurenine, is an important immunoregulatory mechanism underlying immunosuppression, tolerance, and immunity. Recent studies revealed that induction of IDO depends on AHR expression. This review summarizes the most current findings regarding the functions of AHR and IDO in immune cells as they relate to the pathogenesis of autoimmune diseases in response to various stimuli. We also discuss the potential link between AHR and IDO/tryptophan metabolites, and the involvement of several novel related factors (such as microRNA) in the development of autoimmune diseases. These novel factors represent potential therapeutic targets for the treatment of autoimmune disorders. PMID:25400638

Nguyen, Nam Trung; Nakahama, Taisuke; Le, Duc Hoang; Van Son, Le; Chu, Ha Hoang; Kishimoto, Tadamitsu

2014-01-01

302

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

303

Premature atherosclerosis in systemic autoimmune diseases.  

E-print Network

??Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and Wegener’s granulomatosis (WG) are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared… (more)

Leeuw, Karina de

2008-01-01

304

Autoantibodies in pre-clinical autoimmune disease.  

PubMed

The presence of autoantibodies is characteristic of autoimmune diseases. It is widely accepted that autoantibodies provide crucial diagnostic and prognostic information for autoimmune diseases. Indeed, numerous studies have demonstrated that the appearance of autoantibodies precedes the clinical onset of autoimmune diseases. We performed a literature review regarding the appearance of autoantibodies that preceded the clinical onset of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, primary biliary cirrhosis, inflammatory bowel disease, and multiple sclerosis. Herein we review and comment on the major findings of these studies. PMID:24972003

Hu, Zhi-De; Deng, An-Mei

2014-11-01

305

Unmet needs in autoimmunity and potential new tools.  

PubMed

The term "autoimmunity" refers to a pathological condition in which the immunological tolerance of self-antigens is broken through, cross-reactive T cells are activated, and autoantibodies are produced by B cells. The intricate interplay among those aberrantly activated immune cells as well as inflammatory cytokines secreted by them contributes to the development of proinflammatory cascade which eventually leads to the occurrence of autoimmune diseases (AIDs) and organ damage. Autoimmune diseases occupy a broad spectrum of human diseases with more than 70 different disorders and afflict approximately 5-8 % of the world's population. AIDs can be categorized into organ-specific and systemic. Although the exact mechanism of AIDs remains elusive, it is generally believed that both genetic polymorphism and environmental exposure are involved in the development of AIDs. Aberrant epigenetic marks are also identified in patients with AIDs. In addition, dysregulation of innate immune system and molecular mimicry are indicated to play important roles in the initiation and maintenance of autoreactive inflammation. Based on the progress made in elucidating molecular mechanisms underlying AIDs, novel biomarkers for prediction, early diagnosis, prognosis and treatment response, and therapeutic strategies are proposed, which represents a promising future in the battle against AIDs. However, challenges remain regarding the clinical application of these potential new tools. PMID:24595881

Lu, Qianjin

2014-10-01

306

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

307

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

308

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

309

Autoimmune hemolytic anemia in chronic mucocutaneous candidiasis.  

PubMed Central

Chronic mucocutaneous candidiasis is an immunodeficiency disease characterized by T-cell dysregulation and chronic superficial candidal infections. We report on three patients with chronic mucocutaneous candidiasis who developed autoantibodies to erythrocytes. Our first patient, a 19-year-old female, developed autoimmune hemolytic anemia (AIHA) that required multiple courses of treatment, including corticosteroids, intravenous immunoglobulin, and danazol. During the last exacerbation of AIHA, intensive treatment with corticosteroids and intravenous immunoglobulin failed and yet the patient responded to plasmapheresis. Our second patient, a 21-year-old male, developed AIHA which responded to oral corticosteroid therapy. Our third patient, a 6-year-old female without evidence of hemolysis, was found to have erythrocyte autoantibodies on routine screening. These three patients had positive direct antiglobulin tests, and the first patient had both immunoglobulin G (IgG) and IgM erythrocyte autoantibodies, while the remaining two patients had only IgG autoantibody. This is the first report of the association of AIHA with chronic mucocutaneous candidiasis. We suggest that all patients with chronic mucocutaneous candidiasis be screened periodically for erythrocyte autoantibodies. Plasmapheresis, a safe ancillary procedure in the management of AIHA, may be life-saving in some cases. The occurrence of erythrocyte autoantibodies in mucocutaneous candidiasis may be related to immunoregulatory disorders in this disease. PMID:7496919

Oyefara, B I; Kim, H C; Danziger, R N; Carroll, M; Greene, J M; Douglas, S D

1994-01-01

310

T-Cell-Mediated Autoimmunity  

PubMed Central

Histological samples of autopsy or biopsy tissue provide the best available evidence that autoreactive T cells are involved in the immunopathogenesis of many autoimmune diseases. However, morphology alone does not provide information on the antigen-specific T-cell receptor (TCR) of these cells, let alone on their antigen specificity. In this review article we discuss a number of emerging possibilities for identifying TCR sequences directly from biopsy tissue. We also review the methods for expressing presumably autoreactive TCR molecules and speculate on how the expressed TCR might be used to identify target antigens. Such information should eventually provide new insights into disease pathogenesis which lead to better therapies. PMID:14507631

Dornmair, Klaus; Goebels, Norbert; Weltzien, Hans-Ulrich; Wekerle, Hartmut; Hohlfeld, Reinhard

2003-01-01

311

Toxic multinodular goiter: a variant of autoimmune hyperthyroidism.  

PubMed

The aim of this study was to examine whether at least a subgroup of patients with toxic multinodular goiter may have autoimmune thyroid disease. Thyroid-stimulating immunoglobulin (TSI) activity, measured by a sensitive bioassay employing cultured human thyroid cells, was determined in patients with toxic multinodular goiter and other thyroid disorders. All patients with active Graves' disease (n = 47) had detectable serum TSI activity, whereas TSI was undetectable in patients with thyroid disease not believed to be of autoimmune origin: toxic adenoma (n = 13), cold nodule (n = 5), and nontoxic goiter (n = 19), with a single exception in the latter group. Toxic multinodular goiter (n = 26) was diagnosed based on clinical and laboratory evidence of hyperthyroidism associated with a multinodular goiter on palpation and scintiscan. The toxic multinodular goiter group was then subclassified according to scintiscan pattern (type A, diffuse but uneven distribution of technetium uptake; type B, multiple discrete nodules of varying size and function). All but 1 of the 11 TSI-positive toxic multinodular goiter patients had a type A scintiscan pattern. The patients with the type A scintiscan pattern were younger and more often had elevated antithyroid antibody titers, ophthalmopathy, and concurrent development of goiter and hyperthyroidism (rather than long-standing goiter preceding hyperthyroidism) compared to the type B patients. Thus, a subgroup of patients with clinically defined toxic multinodular goiter (type A) probably have autoimmune hyperthyroidism (a variant of Graves' disease), while in another subgroup (type B) hyperthyroidism is not related to an autoimmune etiology (a variant of toxic adenoma). PMID:2888784

Kraiem, Z; Glaser, B; Yigla, M; Pauker, J; Sadeh, O; Sheinfeld, M

1987-10-01

312

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

313

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

314

Helicobacter pylori and skin autoimmune diseases  

PubMed Central

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

Magen, Eli; Delgado, Jorge-Shmuel

2014-01-01

315

Eur J Dermatol . Author manuscript Plasmacytoid dendritic cells and dermatological disorders: focus on their  

E-print Network

disorders: focus on their role in autoimmunity and cancer Julie Charles 1 2 3 , Laurence Chaperot 1 2 been observed in inflammatory immunoallergic dermatological disorders, in malignant cutaneous tumours of the pathological process of autoimmune diseases such as lupus or psoriasis. Their function within a tumour context

Paris-Sud XI, Université de

316

Diagnosis and classification of autoimmune gastritis.  

PubMed

Autoimmune gastritis is a silent and highly prevalent disease that only becomes clinically manifested with progression to corpus atrophy and development of iron deficient or B12-deficient (pernicious) anaemia. Autoimmune gastritis is associated with autoimmune thyroiditis and type 1 diabetes mellitus. Corpus atrophy may be complicated by gastric carcinoids and gastric cancer. Laboratory diagnosis of autoimmune gastritis rests on serum biomarkers of antibody to parietal cell H/K ATPase and intrinsic factor and corpus atrophy on serum biomarkers of gastrin and pepsinogen levels. Subjects with asymptomatic parietal cell antibody should be regularly assessed for serum biomarkers for progression to corpus atrophy, development of iron and B12 deficiency anaemia and for associated autoimmune thyroiditis and type 1 diabetes mellitus. PMID:24424193

Toh, Ban-Hock

2014-01-01

317

Hepatitis C virus infection and autoimmunity.  

PubMed

Hepatitis C virus (HCV) infection has been associated with a plethora of immune and autoimmune perturbations. We review serological and clinical autoimmune manifestations associated with HCV infection, discuss treatment regimens for HCV-related autoimmune diseases, and present a framework for understanding HCV-associated autoimmune disease by performing a computerized literature search from which representative articles were used and referenced. The immune response to HCV may include the development of cryoglobulins, rheumatoid factor, antinuclear antibodies (ANA), anticardiolipin, antithyroid, anti-liver/kidney/microsomal antibodies (anti-LKM), as well as HCV/anti-HCV immune complex formation and deposition. HCV infection is a significant cause of mixed essential cryoglobulinemia, which may then be complicated by cryoglobulinemic glomerulonephritis, vasculitis, or neuropathy. It has also been associated with membranous and membranoproliferative glomerulonephritis. Subsets of autoimmune hepatitis patients are infected with HCV and evidence suggests that HCV is a causative agent of antithyroid antibodies and autoimmune thyroid disease. Although cause-and-effect remain to be proved, there are reports of HCV infection preceding or coincident with polyarthritis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and polymyositis/dermatomyositis (PM/DM). HCV-infected patients also have a high incidence of sialoadenitis, and reports of low-grade lymphoproliferative malignancies have emerged. However, HCV is not a major causative factor for most autoimmune diseases. Optimal treatment for HCV-related autoimmune disease remains to be determined. Interferon alpha (IFN alpha) has successfully reduced viremia/transaminitis, cryoglobulins, proteinuria, and nephritis, but recurrent disease manifestations are frequent after discontinuation of therapy. Moreover, IFN alpha may precipitate or exacerbate autoimmune disease symptoms. HCV-related autoimmune disease also has been treated successfully with corticosteroids, azathioprine, and cyclophosphamide, although HCV viremia persists and may worsen. PMID:9062950

McMurray, R W; Elbourne, K

1997-02-01

318

Low dose combination steroids control autoimmune mouse hearing loss.  

PubMed

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 dose fludrocortisone, a synthetic mineralocorticoid that also has a slight glucocorticoid effect. MRL/MpJ-Fas(lpr) mice were tested for baseline ABR thresholds at 3 months of age and then treated with aldosterone (3.0 ?g/kg) or prednisolone (1.0 mg/kg) to determine the lowest effective dose of each. Other mice were given the two steroids in combination at doses of Pred 0.5 mg+Aldo 1.5 ?g; Pred 1.0 mg+Aldo 3.0 ?g; or Pred 1.5 mg+Aldo 5.0 ?g. Mice were retested with ABR at 1 and 2 months to determine the efficacy of the different steroid treatments in controlling hearing loss. Another series of mice were given the synthetic mineralocorticoid fludrocortisone at low (2.8 ?g/kg) or high (10 ?g/kg) doses and retested at monthly intervals for 3 months. Autoimmune mouse hearing loss developed in untreated controls. This threshold elevation was not prevented by prednisolone at 1 mg/kg or by aldosterone at 3 ?g/kg when each was given alone. However, the two steroids combined at these doses effectively controlled hearing loss. The fludrocortisone treatments also were effective at low doses in preventing or reversing the autoimmune mouse hearing loss. This efficacy of combined steroids at low doses suggests the potential for reducing the side effects of glucocorticoids in the therapeutic control of hearing disorders. PMID:20800906

Trune, Dennis R; Kempton, J Beth

2010-12-15

319

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

320

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

321

Autoimmune pancreatitis: a case report.  

PubMed

Autoimmune pancreatitis is a fibro-inflammatory form of chronic pancreatitis. It is diagnosed by the combination of imaging studies such as a CT scan and pancreatography, laboratory analyses that include IgG4 and/or autoantibodies, histopathological evaluations and positive response to corticosteroid therapy. We report the case of a 41-year-old female with a history of jaundice and increasing abdominal pain for two weeks prior to her clinic visit. Laboratory results were significant for an increase in alkaline phosphatase (ALP) and erythrocyte sedimentation rate (ESR). Magnetic resonance cholangiopancreatography (MRCP) confirmed areas of stenosis and dilatation in the pancreatic duct and in the intra- and extra-hepatic bile ducts similar to primary sclerosantcholangitis. Laboratory analyses showed increased levels of IgG4 with thepresence of antinuclear antibodies. PMID:24829705

Salari, Masoumeh; Hosseini, Mousareza; Nekooei, Sirous; Ataei Azimi, Sajad; Farzanehfar, Mohammad Reza

2014-01-01

322

Autoimmune Pancreatitis: A Case Report  

PubMed Central

Autoimmune pancreatitis is a fibro-inflammatory form of chronic pancreatitis. It is diagnosed by the combination of imaging studies such as a CT scan and pancreatography, laboratory analyses that include IgG4 and/or autoantibodies, histopathological evaluations and positive response to corticosteroid therapy. We report the case of a 41-year-old female with a history of jaundice and increasing abdominal pain for two weeks prior to her clinic visit. Laboratory results were significant for an increase in alkaline phosphatase (ALP) and erythrocyte sedimentation rate (ESR). Magnetic resonance cholangiopancreatography (MRCP) confirmed areas of stenosis and dilatation in the pancreatic duct and in the intra- and extra-hepatic bile ducts similar to primary sclerosantcholangitis. Laboratory analyses showed increased levels of IgG4 with thepresence of antinuclear antibodies. PMID:24829705

Salari, Masoumeh; Hosseini, Mousareza; Nekooei, Sirous; Ataei Azimi, Sajad; Farzanehfar, Mohammad Reza

2014-01-01

323

Is hypertension an autoimmune disease?  

PubMed

T cells are required for significant blood pressure elevation in mouse models of hypertension. Recent evidence suggests that the treatments that raise blood pressure in these animal models also cause oxidation within DCs, resulting in formation of isoketal adducts of self-proteins, which activate antigen-presenting functions of these cells and serve as a source of modified self-antigens. T cells specific for these modified self-antigens then produce cytokines that promote blood pressure elevation, consistent with the idea that hypertension is an autoimmune response to altered self. Here, I will review the new evidence for this idea put forth by Kirabo and colleagues in this issue of the JCI, identify a number of as yet unanswered questions, and discuss some of the therapeutic implications. PMID:25244091

Pober, Jordan S

2014-10-01

324

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

325

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

326

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

327

Is Multiple Sclerosis an Autoimmune Disease?  

PubMed Central

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS. PMID:22666554

Wootla, Bharath; Eriguchi, Makoto; Rodriguez, Moses

2012-01-01

328

Cutting edge issues in autoimmune gastritis.  

PubMed

Autoimmune gastritis is the outcome of a pathological CD4 T cell-mediated autoimmune response directed against the gastric H/K-ATPase. Silent initially, the gastric lesion becomes manifest in humans by the development of megaloblastic pernicious anemia arising from vitamin B12 deficiency. Cutting edge issues in this disease relate to its epidemiology, immunogenetics, a role for Helicobacter pylori as an infective trigger through molecular mimicry, its immunopathogenesis, associated organ-specific autoimmune diseases, laboratory diagnosis, and approaches to curative therapy. PMID:21174235

Toh, Ban-Hock; Chan, James; Kyaw, Tin; Alderuccio, Frank

2012-06-01

329

Autoimmune cytopenias in chronic lymphocytic leukemia.  

PubMed

Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary autoimmune cytopenias (AIC) represented by autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia, and autoimmune granulocytopenia. The distinction of immune cytopenias from cytopenias due to bone marrow infiltration, usually associated with a worse outcome and often requiring a different treatment, is mandatory. AIHA and ITP are more frequently found in patients with unfavorable biological risk factors for CLL. AIC secondary to CLL respond less favorably to standard treatments than their primary forms, and treating the underlying CLL with chemotherapy or monoclonal antibodies may ultimately be necessary. Am. J. Hematol. 89:1055-1062, 2014. © 2014 Wiley Periodicals, Inc. PMID:24912821

Visco, Carlo; Barcellini, Wilma; Maura, Francesco; Neri, Antonino; Cortelezzi, Agostino; Rodeghiero, Francesco

2014-11-01

330

Validation of scoring system for diagnosis of autoimmune hepatitis  

Microsoft Academic Search

To assess the validity of a scoring system developed by the International Autoimmune Hepatitis Group for the definite diagnosis of autoimmune hepatitis, 119 patients with autoimmune hepatitis by standard clinical criteria and 131 patients with other chronic liver diseases were evaluated. Each patient was graded on 35 items in 13 clinical categories. Ninety-seven patients diagnosed as having autoimmune hepatitis by

Albert J. Czaja; Herschel A. Carpenter

1996-01-01

331

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

PubMed Central

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

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

2006-01-01

332

Pityriasis rubra pilaris presenting with an abnormal autoimmune profile: two case reports  

PubMed Central

Introduction Pityriasis rubra pilaris is an uncommon inflammatory and hyperproliferative dermatosis of juvenile or adult onset. The etiology of the disease is still unknown. Case presentation We present the cases of two Caucasian men aged 53 and 48 who presented with pityriasis rubra pillaris type 1; both patients also exhibited an abnormal immunological profile. Conclusion Pityriasis rubra pillaris is currently classified as a keratinization disorder. The abnormal immunological profile reported in our patients along with the comorbidity of pityriasis rubra pilaris with autoimmune disorders reported in the literature poses the question of a possible pathogenetic role for the immune response in this disorder. PMID:19946540

2009-01-01

333

Autoimmune and autoinflammatory mechanisms in uveitis  

PubMed Central

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.

2014-01-01

334

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

335

Celiac disease and autoimmune-associated conditions.  

PubMed

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

336

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

337

[Cross-autoimmune syndromes in hepatology].  

PubMed

Along with the traditional autoimmune liver diseases--autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC)--in clinical practice there are syndromes of autoimmune decussating. The term cross-syndrome means that in one patient there are signs of two different autoimmune liver diseases, that probably have a common pathogenesis. In line with the literature data and own experience of the diagnostic criteria there are different cross-syndromes: AIH and PBC, AIH and PSC; and also a combination of AIH and chronic hepatitis C. The most appropriate combinations and doses of prednisolone (budesonid), azathioprine and ursodesoxycholic acid, recommended for treatment of various options of cross-syndrome, as well as medical tactics in view of the conjunction of AIH and chronic hepatitis C, have been considered. PMID:24294777

Podymova, S D

2013-01-01

338

Is schizophrenia an autoimmune disease? A review.  

PubMed

Autoimmunity has been shown to be the basis of an ever-increasing number of human diseases. Schizophrenia shares a number of genetic features with these autoimmune diseases and therefore could be an autoimmune disease itself. Several lines of evidence suggest that overactivity of dopaminergic pathways in some areas of the brain are involved in schizophrenia, but the apparent absence of an increase in dopamine turnover suggests that this hyperactivity could be mediated by a dopamine agonist rather than by dopamine itself. Schizophrenia is reviewed in the light of precedents from the field of autoimmune diseases in which autoantibodies have been shown to be able to interact with, and sometimes stimulate hormone receptors, thereby causing disease. PMID:6390022

Knight, J G

1984-07-01

339

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

340

Heat shock proteins and autoimmunity in humans  

Microsoft Academic Search

Summary T cells and antibodies against self and non-self hsp are present in both patients and healthy controls. T cells responding to hsp65 can be involved in autoimmune diseases, this was demonstrated for two site-specific animal autoimmune diseases: AA in Lewis rats and diabetes (IDDM) in NOD mice. In human ReA there is evidence for a direct stimulation of joint

Pieter Res; Jelle Thole; René de Vries

1991-01-01

341

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

342

Natural antibody mediated innate autoimmune response  

Microsoft Academic Search

Recent advance in autoimmunity research reveals that the innate immune system is able to recognize self-targets and initiate inflammatory response in a similar way as with pathogens. This review describes one novel example of this innate autoimmunity, ischemia–reperfusion (I\\/R) injury. Studies of intestinal, skeletal muscle, and heart I\\/R models showed that reperfusion of ischemic tissues elicits an acute inflammatory response

Ming Zhang; Michael C. Carroll

2007-01-01

343

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

344

NK Cell Autoreactivity and Autoimmune Diseases  

PubMed Central

Increasing evidences have pointed out the relevance of natural killer (NK) cells in organ-specific and systemic autoimmune diseases. NK cells bear a plethora of activating and inhibiting receptors that can play a role in regulating reactivity with autologous cells. The activating receptors recognize natural ligands up-regulated on virus-infected or stressed or neoplastic cells. Of note, several autoimmune diseases are thought to be linked to viral infections as one of the first event in inducing autoimmunity. Also, it is conceivable that autoimmunity can be triggered when a dysregulation of innate immunity occurs, activating T and B lymphocytes to react with self-components. This would imply that NK cells can play a regulatory role during adaptive immunity; indeed, innate lymphoid cells (ILCs), comprising the classical CD56+ NK cells, have a role in maintaining or alternating tissue homeostasis secreting protective and/or pro-inflammatory cytokines. In addition, NK cells display activating receptors involved in natural cytotoxicity and the activating isoforms of receptors for HLA class I that can interact with healthy host cells and induce damage without any evidence of viral infection or neoplastic-induced alteration. In this context, the interrelationship among ILC, extracellular-matrix components, and mesenchymal stromal cells can be considered a key point for the control of homeostasis. Herein, we summarize evidences for a role of NK cells in autoimmune diseases and will give a point of view of the interplay between NK cells and self-cells in triggering autoimmunity. PMID:24550913

Poggi, Alessandro; Zocchi, Maria Raffaella

2014-01-01

345

Involvement of endocrine system in a patient affected by glycogen storage disease 1b: speculation on the role of autoimmunity.  

PubMed

Glycogen storage disease type 1b (GSD1b) is an inherited metabolic defect of glycogenolysis and gluconeogenesis due to mutations of the SLC37A4 gene and to defective transport of glucose-6-phosphate. The clinical presentation of GSD1b is characterized by hepatomegaly, failure to thrive, fasting hypoglycemia, and dyslipidemia. Patients affected by GSD1b also show neutropenia and/or neutrophil dysfunction that cause increased susceptibility to recurrent bacterial infections. GSD1b patients are also at risk for inflammatory bowel disease. Occasional reports suggesting an increased risk of autoimmune disorders in GSD1b patients, have been published. These complications affect the clinical outcome of the patients. Here we describe the occurrence of autoimmune endocrine disorders including thyroiditis and growth hormone deficiency, in a patient affected by GSD1b. This case further supports the association between GSD1b and autoimmune diseases. PMID:24646511

Melis, Daniela; Della Casa, Roberto; Balivo, Francesca; Minopoli, Giorgia; Rossi, Alessandro; Salerno, Mariacarolina; Andria, Generoso; Parenti, Giancarlo

2014-01-01

346

Involvement of endocrine system in a patient affected by Glycogen storage disease 1b: speculation on the role of autoimmunity  

PubMed Central

Glycogen storage disease type 1b (GSD1b) is an inherited metabolic defect of glycogenolysis and gluconeogenesis due to mutations of the SLC37A4 gene and to defective transport of glucose-6-phosphate. The clinical presentation of GSD1b is characterized by hepatomegaly, failure to thrive, fasting hypoglycemia, and dyslipidemia. Patients affected by GSD1b also show neutropenia and/or neutrophil dysfunction that cause increased susceptibility to recurrent bacterial infections. GSD1b patients are also at risk for inflammatory bowel disease. Occasional reports suggesting an increased risk of autoimmune disorders in GSD1b patients, have been published. These complications affect the clinical outcome of the patients. Here we describe the occurrence of autoimmune endocrine disorders including thyroiditis and growth hormone deficiency, in a patient affected by GSD1b. This case further supports the association between GSD1b and autoimmune diseases. PMID:24646511

2014-01-01

347

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

348

Autoimmune Dementia: Clinical Course and Predictors of Immunotherapy Response  

PubMed Central

OBJECTIVE: To define the diagnostic characteristics and predictors of treatment response in patients with suspected autoimmune dementia. PATIENTS AND METHODS: Between January 1, 2002, and January 1, 2009, 72 consecutive patients received immunotherapy for suspected autoimmune dementia. Their baseline clinical, radiologic, and serologic characteristics were reviewed and compared between patients who were responsive to immunotherapy and those who were not. Patients were classified as responders if the treating physician had reported improvement after immunotherapy (documented in 80% by the Kokmen Short Test of Mental Status, neuropsychological testing, or both). RESULTS: Initial immunotherapeutic regimens included methylprednisolone in 56 patients (78%), prednisone in 12 patients (17%), dexamethasone in 2 patients (3%), intravenous immune globulin in 1 patient (1%), and plasma exchange in 1 patient (1%). Forty-six patients (64%) improved, most in the first week of treatment. Thirty-five percent of these immunotherapy responders were initially diagnosed as having a neurodegenerative or prion disorder. Pretreatment and posttreatment neuropsychological score comparisons revealed improvement in almost all cognitive domains, most notably learning and memory. Radiologic or electroencephalographic improvements were reported in 22 (56%) of 39 patients. Immunotherapy responsiveness was predicted by a subacute onset (P<.001), fluctuating course (P<.001), tremor (P=.007), shorter delay to treatment (P=.005), seropositivity for a cation channel complex autoantibody (P=.01; neuronal voltage-gated potassium channel more than calcium channel or neuronal acetylcholine receptor), and elevated cerebrospinal fluid protein (>100 mg/dL) or pleocytosis (P=.02). Of 26 immunotherapy-responsive patients followed up for more than 1 year, 20 (77%) relapsed after discontinuing immunotherapy. CONCLUSION: Identification of clinical and serologic clues to an autoimmune dementia allows early initiation of immunotherapy, and maintenance if needed, thus favoring an optimal outcome. PMID:20884824

Flanagan, Eoin P.; McKeon, Andrew; Lennon, Vanda A.; Boeve, Bradley F.; Trenerry, Max R.; Tan, K. Meng; Drubach, Daniel A.; Josephs, Keith A.; Britton, Jeffrey W.; Mandrekar, Jayawant N.; Lowe, Val; Parisi, Joseph E.; Pittock, Sean J.

2010-01-01

349

Transplantation in autoimmune liver diseases  

PubMed Central

Liver transplantation remains an effective treatment for those with end-stage disease and with intractable liver-related symptoms. The shortage of organs for transplantation has resulted in the need for rationing. A variety of approaches to selection and allocation have been developed and vary from country to country. The shortage of donors has meant that new approaches have to be adopted to make maximal use of the available organs; these include splitting grafts, use of extended criteria livers, livers from non-heart-beating donors and from living donors. Post transplantation, most patients will need life-long immunosuppression, although a small proportion can have immunosuppression successfully withdrawn. Newer immunosuppressive drugs and different strategies may allow a more targeted approach with a reduction in side-effects and so improve the patient and graft survival. For autoimmune diseases, transplantation is associated with significant improvement in the quality and length of life. Disease may recur after transplantation and may affect patient and graft survival. PMID:18528936

Mottershead, Marcus; Neuberger, James

2008-01-01

350

Tic disorders: neural circuits, neurochemistry, and neuroimmunology.  

PubMed

The neuroanatomy and neurochemistry underlying tic disorders are thought to involve corticostriatothalamocortical circuits and dysregulation of their component neurotransmitter systems. Tourette syndrome is a tic disorder that begins in childhood and follows a waxing and waning course of tic severity. Although it is generally believed to have a genetic component, its etiology has not been fully elucidated. The clinical entity pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) has led some to suggest that the pathophysiology of tics in some individuals might involve a postinfectious autoimmune component. We review the neural circuits and neurochemistry of Tourette syndrome and evaluate the evidence for and against a role for autoimmunity in the expression of tics. PMID:16970869

Harris, Kendra; Singer, Harvey S

2006-08-01

351

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

352

Platelets contribute to the pathogenesis of experimental autoimmune encephalomyelitis  

PubMed Central

Rationale Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), are inflammatory disorders of the central nervous system (CNS). The function of platelets in inflammatory and autoimmune pathologies is thus far poorly defined. Objective Here we addressed the role of platelets in mediating CNS inflammation in EAE. Results We found that platelets were present in human MS lesions as well as in the CNS of mice subjected to EAE but not in the CNS from control non-diseased mice. Platelet depletion at the effector-inflammatory phase of EAE in mice resulted in significantly ameliorated disease development and progression. EAE suppression upon platelet depletion was associated with reduced recruitment of leukocytes to the inflamed CNS, as assessed by intravital microscopy, and with a blunted inflammatory response. The platelet-specific receptor glycoprotein Ib alpha (GPIb?) promotes both platelet adhesion as well as inflammatory actions of platelets, and, targeting of GPIb? attenuated EAE in mice. Moreover, targeting another platelet adhesion receptor, glycoprotein IIb/IIIa (GPIIb/IIIa) also reduced EAE severity in mice. Conclusions Thus, platelets contribute to the pathogenesis of EAE by promoting CNS inflammation. Targeting platelets may therefore represent an important new therapeutic approach for MS treatment. PMID:22456181

Langer, Harald F.; Choi, Eun Young; Zhou, Hong; Schleicher, Rebecca; Chung, Kyoung-Jin; Tang, Zhongshu; Gobel, Kerstin; Bdeir, Khalil; Chatzigeorgiou, Antonios; Wong, Connie; Bhatia, Sumeena; Kruhlak, Michael J.; Rose, John W.; Burns, James B.; Hill, Kenneth E.; Qu, Hongchang; Zhang, Yongqing; Lehrmann, Elin; Becker, Kevin G.; Wang, Yunmei; Simon, Daniel I.; Nieswandt, Bernhard; Lambris, John D.; Li, Xuri; Meuth, Sven G.; Kubes, Paul; Chavakis, Triantafyllos

2012-01-01

353

Expansion of CD4CD25 regulatory T cells by intravenous immunoglobulin: a critical factor in controlling experimental autoimmune encephalomyelitis  

Microsoft Academic Search

The clinical use of intravenous immuno- globulin (IVIg) based on its immuno- modulatory and anti-inflammatory poten- tial remains an ongoing challenge. Fc receptor-mediated effects of IVIg, al- though well elucidated in certain patholo- gies, cannot entirely account for its proven benefit in several autoimmune disorders mediated by autoreactive T cells. In this study, we show that prophy- lactic infusion of

Amal Ephrem; Catherine Miquel; Sylvain Fisson; Luc Mouthon; Giuseppina Caligiuri; Sandrine Delignat; Sriramulu Elluru; Jagadeesh Bayry; Sebastien Lacroix-Desmazes; Benoît L. Salomon; Michel D. Kazatchkine; Srini V. Kaveri; Namita Misra; Marie Curie-Paris

2010-01-01

354

Immunosuppressive activity of a novel peptide analog of alpha-melanocyte stimulating hormone (?-MSH) in experimental autoimmune uveitis  

Microsoft Academic Search

Autoimmune uveitis is an inflammatory disorder of the eye that can lead to pain and vision loss. Steroids and immunosuppressive drugs are currently the only therapeutics for uveitis and have serious ocular and systemic toxicities. Therefore, safer alternative therapeutics are desired. Alpha-melanocyte stimulating hormone (?-MSH) is a neuropeptide that suppresses effector T cell functions, induces regulatory T cells and has

Andrea E. Edling; Danilo Gomes; Timothy Weeden; John Dzuris; Jim Stefano; Clark Pan; John Williams; Johanne Kaplan; Michael A. Perricone

2011-01-01

355

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

356

Expert panel workshop consensus statement on the role of the environment in the development of autoimmune disease.  

PubMed

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

357

Autoimmune diseases detected in children with primary immunodeficiency diseases: results from a reference centre at middle anatolia.  

PubMed

Primary immunodeficiency diseases (PIDs) are a heterogeneous group of disorders that genetically affect distinct components of the immune system; thus, predispose individuals to recurrent infections, allergy, autoimmunity, and malignancies. In this retrospective study, autoimmune diseases (ADs), which developed during the course of PID in children, were discussed.Twenty-five patients were included in this study. Symptoms related to ADs, such as autoimmune thyroiditis, type 1 diabetes mellitus, coeliac disease, juvenile idiopathic arthritis, dermatomyositis, autoimmune haemolytic anaemia, leukocytoclastic vasculitis, Henoch-Schonlein purpura, hypoparathyroidism, alopecia areata, Addison's disease, vitiligo and systemic lupus erythematosus were detected in these patients, who have been followed with diagnosis of PID including common variable immunodeficiency, selective and partial IgA deficiency, Wiskott-Aldrich syndrome, ataxia telangiectasia, hyperimmunoglobulin E syndrome, chronic mucocutaneous candidiasis, Griscelli syndrome, and partial C4 deficiency.Immunodeficiency and autoimmune phenomenon may concomitantly present in an individual, although they seem to be incompatible ends in the spectrum of the clinical immune response. Patients with primary immune deficiency should be closely monitored for development of autoimmune diseases. PMID:22982638

Patiroglu, Turkan; Gungor, Hatice Eke; Unal, Ekrem

2012-09-01

358

REGULATION OF CENTRAL NERVOUS SYSTEM AUTOIMMUNITY BY THE ARYL HYDROCARBON RECEPTOR  

PubMed Central

The ligand-activated transcription factor aryl hydrocarbon receptor controls the activity of several components of the immune system, many of which play an important role in neuroinflammation. This review discusses the role of AhR in T cells and dendritic cells, its relevance for the control of autoimmunity in the central nervous system, and its potential as a therapeutic target for immune mediated disorders. PMID:23999753

Quintana, Francisco J.

2013-01-01

359

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

360

511ISSN 1745-5057Women's Health (2010) 6(4), 51151610.2217/WHE.10.45 2010 Future Medicine Ltd autoimmune diseases (e.g., rheumatoid arthri-  

E-print Network

autoimmune diseases (e.g., rheumatoid arthri- tis, lupus and multiple sclerosis), asthma and several types mental disorders (e.g., major depressive disor- der, schizophrenia, autism, eating disorders and attention-deficit hyperactivity disorder), PERSPECTIVE Sex and sensitivity: the continued need for sex

Chisholm, Rex L.

361

Autoantibody-associated movement disorders.  

PubMed

Autoantibodies to the extracellular domain of neuronal proteins cause different neurological conditions with movement disorders as a prominent feature. We reviewed the literature of autoantibody-mediated and autoantibody-associated diseases focusing on anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, autoimmune basal ganglia encephalitis, Sydenham chorea, and the rare syndrome of progressive encephalomyelitis with rigidity and myoclonus. NMDAR encephalitis is a diffuse encephalitis with psychiatric and cognitive features associated with autoantibodies against the NR1 subunit of the NMDAR. The movement disorder phenotype is diverse and often generalized in young children. Although orofacial dyskinesia was the initial movement phenotype, chorea, dystonia, catatonia, and stereotypical movements are now described. The stereotypical movements can be bizarre and include cycling movements and compulsive self-injurious behavior. Autoimmune basal ganglia encephalitis is an inflammatory encephalitis localizing to the basal ganglia that is sometimes associated with serum antibodies against dopamine-2 receptor. Although psychiatric features are common, the dominant problem is a movement disorder, with dystonia-parkinsonism being characteristic. Sydenham chorea is the prototypic poststreptococcal autoimmune neuropsychiatric disorder and several autoantibodies may be involved in disease generation. The syndrome is characterized by a pure chorea, although hypotonia, dysarthria, and emotional lability are common. Progressive encephalomyelitis with rigidity and myoclonus is a rare autoimmune disorder causing rigidity, stimulus sensitive spasms, and myoclonus of nonepileptic origin and is associated with autoantibodies of multiple types including those against the glycine receptor. These disorders are important to recognize and diagnose, as immune therapy can shorten disease duration and improve outcome. PMID:24203856

Mohammad, Shekeeb S; Ramanathan, Sudarshini; Brilot, Fabienne; Dale, Russell C

2013-12-01

362

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

363

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

364

Virus-mediated autoimmunity in Multiple Sclerosis  

PubMed Central

Epidemiological data suggest the notion that in Multiple Sclerosis (MS) is an acquired autoimmune disease and the cause may be an environmental factor(s), probably infectious, in genetically susceptible individuals. Several cases of viral induced demyelinatimg encephalomyelitis in human beings and in experimental models as well as the presence of IgG oligoclonal bands in the cerebrospinal fluid indicate that the infectious factor may be viral. However, the absence of a specific virus identification in MS central nervous system may hardly support this notion. On the other hand, the partial response of patients with MS to immunosuppressive and immunomodulatory therapy support the evidence of an autoimmune etiology for MS. However, the autoimmune hypothesis shares the same criticism with the infectious one in that no autoantigen(s) specific to and causative for MS has ever been identified. Nevertheless, the absence of identifiable infectious agent, especially viral does not rule out its presence at a certain time – point and the concomitant long term triggering of an autoimmune cascade of events thereafter. Several concepts have emerged in an attempt to explain the autoimmune mechanisms and ongoing neurodegeneration in MS on the basis of the infectious – viral hypothesis. PMID:16504001

Grigoriadis, Nikolaos; Hadjigeorgiou, Georgios M

2006-01-01

365

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

366

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

367

Immunity and schizophrenia: autoimmunity, cytokines, and immune responses.  

PubMed

As is evident from the present account, there is no single or persuasive argument that signals emanating from the immune system are directly involved in the etiology of schizophrenia. We do not even know if we are dealing with a single disorder with a single causality; almost certainly we are not. The precise etiology of schizophrenia, as with so many neurological disorders, remains obscure. However, there is abundant evidence in schizophrenia of mutual dysregulation of neuronal function and immune system activity. Although this evidence is not always consistent, a pattern emerges suggesting aspects of immune activity being involved in the pathology of neuronal development that characterizes schizophrenia. Exposure to infective agents, HLA associations, autoimmune associations, disturbances in lymphocyte populations, and cytokine imbalances with a skew toward Th2 activity are supportive of this view. That the evidence is not always consistent is a testament to the complexity and heterogeneity of the disorder, to confounding by antipsychotics that themselves are immunomodulatory, and to the multifaceted nature, with all its checks and balances, of the immune system itself. PMID:12498108

Gaughran, Fiona

2002-01-01

368

Is gulf war syndrome an autoimmune disorder of endogenous neuropeptides, exogenous sandfly maxadilan and molecular mimicry? 1 The author declares no grants or financial conflict of interest are relevant in the development of this paper. Abstracts from PubMed, National Library of Medicine, were used in the development of this paper. 1  

Microsoft Academic Search

Gulf war syndrome (GWS) remains a contentious diagnosis with conflicting laboratory investigation and lack of a biologically plausible aetiology. This paper discusses the potential role of maxadilan, a potent sandfly vasoactive peptide, in causing autoimmune responses in susceptible individuals through possible molecular mimicry with pituitary adenylate cyclase activating polypeptide (PACAP) and the PAC1R receptor.Gulf war syndrome may share some causative

Donald R Staines

2004-01-01

369

[Autoimmune liver disease: diagnosis and therapy].  

PubMed

Autoimmune Hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and overlap syndromes of these three disease entities are regarded as autoimmune liver diseases. These conditions are important differential diagnoses of elevated liver function tests as about 10 % of liver transplantations in Europe and North America are for these indications. The diagnosis is often difficult but can be facilitated by sequential measurement of relevant autoantibodies, exclusion of other liver disease, ultrasound, ERCP and liver histology. In AIH immunosuppressive therapy has been shown to prevent or stop the development of cirrhosis and improve the prognosis of the patients decisively. In other autoimmune liver diseases this evidence is missing making individual therapeutic decisions necessary. Ursodesoxycholic acid (UDCA) seems to slow disease progression in particular in early stages of PBC. PMID:14997400

Bayer, E M; Schramm, C; Kanzler, S; Lohse, A W

2004-01-01

370

Autoimmune disease triggered by infection with alphaproteobacteria  

PubMed Central

Despite having long been postulated, compelling evidence for the theory that microbial triggers drive autoimmunity has only recently been reported. A specific association between Novosphingobium aromaticivorans, an ubiquitous alphaproteobacterium, and primary biliary cirrhosis (PBC) has been uncovered in patients with PBC. Notably, the association between Novosphingobium infection and PBC has been confirmed in a mouse model in which infection leads to the development of liver lesions resembling PBC concomitant with the production of anti-PDC-E2 antibodies that cross-react with conserved PDC-E2 epitopes shared by Novosphingobium. The discovery of infectious triggers of autoimmunity is likely to change our current concepts about the etiology of various autoimmune syndromes and may suggest new and simpler ways to diagnose and treat these debilitating diseases. PMID:20161124

Mohammed, Javid P; Mattner, Jochen

2009-01-01

371

Hepatitis B virus (HBV) and autoimmune disease.  

PubMed

The etiology and pathogenesis of autoimmune diseases have long been an enigmatic subject that have involved genetic and environmental factors. Recent intriguing data has contributed to the mechanisms involved, including the relationship of infectious agents and loss of tolerance. This loss of tolerance is illustrated by the data on the immune response to Hepatitis B virus such as the molecular mimicry between HBV antigens and self proteins, the generation of immune complexes between HBV antigens and antibodies, and apoptosis/tissue damage resulting in the exposure of intracellular antigens to the immune system. In this paper, we review the current database related to HBV infection and a variety of autoimmune conditions, including autoimmune hepatitis, systemic lupus erythematosus, aplastic anemia, antiphospholipid syndrome, polyarteritis nodosa, rheumatoid arthritis, type 1 diabetes, multiple sclerosis, thyroid disease and uveitis. PMID:18270862

Maya, Ram; Gershwin, M Eric; Shoenfeld, Yehuda

2008-02-01

372

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

373

[Ludwig van Beethoven: an autoimmune deafness?].  

PubMed

The author reminds us of the great moments of Beethoven's life and of the different stages of his deafness onset, until to last instants. The post-mortem examination, performed by doctor Wagner, and the scientific studies of the remains, during the exhumations, are reported. Beethoven's deafness was clearly a sensorineural impairment and the previously suggested prevalent hypotheses are discussed. A new theory is emphasized, based on modern studies about autoimmune sensorineural hearing losses in relation with chronic inflammatory bowel ailment. Conclusion is that Beethoven's deafness was probably owing to a primary autoimmune degeneration of the organ of Corti, giving rise to atrophy of the auditory nerve. PMID:11615339

Davies, P J

1995-01-01

374

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

375

Autoimmune Manifestations in Common Variable Immunodeficiency  

Microsoft Academic Search

Introduction  About 20% of subjects with common variable immune deficiency (CVID) develop an autoimmune complication, most often immune\\u000a thrombocytopenia or hemolytic anemia. While the pathogenesis of autoreactivity is unknown for CVID subjects in general, and\\u000a to a greater extent in those with autoimmunity, there is a loss of switched memory B cells.\\u000a \\u000a \\u000a \\u000a Discussion  About 7–8% of CVID subjects have mutations in the

C. Cunningham-Rundles

2008-01-01

376

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

PubMed

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

2014-09-21

377

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

378

Lymphatic Disorders  

MedlinePLUS

... com Sections in Patients & Caregivers Blood Disorders Bone, Joint, and Muscle Disorders Brain, Spinal Cord, and Nerve Disorders Cancer Children's Health Issues Digestive Disorders Disorders of Nutrition Drugs ...

379

AntiInterferon Autoantibodies in Autoimmune Polyendocrinopathy Syndrome Type 1  

Microsoft Academic Search

BackgroundThe 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

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

2006-01-01

380

Autoantibodies and their Cytoplasmic Antigens in Autoimmune Chronic Active Hepatitis  

Microsoft Academic Search

\\u000a A loss of tolerance against autologous liver tissue is regarded as the principal pathogenetic mechanism in autoimmune liver\\u000a diseases. Autoimmune type chronic active hepatitis (AI-CAH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis\\u000a (PSC) are the three major autoimmune liver diseases. While the primary target of tissue destruction in autoimmune chronic\\u000a active hepatitis is the hepatocyte, biliary tract epithelia are

M. P. Manns; K.-H. Meyer Zum Büschenfelde

381

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; also known  

E-print Network

of other autoimmune manifestations, including thyroiditis, type 1 diabetes, ovarian failure and hepatitisAutoimmune polyendocrinopathy-candidiasis- ectodermal dystrophy (APECED; also known as APS1 at this locus was termed AIRE (autoimmune regulator). It is a large protein of 545 amino acids with several

Cai, Long

382

Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis  

Microsoft Academic Search

Autoimmune hepatitis is a form of chronic liver disease characterized by progressive hepatocellular inflammation, which usually responds to treatment with corticosteroids. However, 10% of patients with autoimmune hepatitis are refractory to corticosteroids and develop progressive liver disease and cirrhosis. We describe five patients with autoimmune hepatitis who did not respond to conventional corticosteroids and azathioprine therapy who were then treated

Neville F Fernandes; Allan G Redeker; John M Vierling; Federico G Villamil; Tse-Ling Fong

1999-01-01

383

Alteration of the lung parenchyma associated with autoimmune hepatitis  

Microsoft Academic Search

Summary The clinical history, radiological and histomorphological alterations of the lung parenchyma associated with chronic active autoimmune hepatitis are described. A 6-month-old female infant developed chronic active autoimmune hepatitis associated with autoimmune haemolytic anaemia. She was treated with immunosuppressive drugs, including steroids, for more than 6 years and developed symptoms and radiological signs of interstitial pneumonitis 4 years after onset

K. Kayser; K. Paul; D. Feist; W. Hofmann; L. Wille; H.-J. Gabius

1991-01-01

384

Autoimmune diseases in the pedigrees of schizophrenic and control subjects  

Microsoft Academic Search

Autoimmune diseases aggregate in individuals and within pedigrees, and it has been postulated that autoimmune mechanisms may account for a proportion of schizophrenia. Structured questionnaires were used to interview the mothers of 121 DSM-III-R schizophrenic patients and the mothers of 116 controls in order to determine the prevalence of schizophrenia and of autoimmune diseases in their pedigrees. Patients with a

Padraig Wright; Pak C. Sham; Catherine M. Gilvarry; Peter B. Jones; Mary Cannon; Tonmoy Sharma; Robin M. Murray

1996-01-01

385

Requirements for innate immune pathways in environmentally induced autoimmunity  

PubMed Central

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

2013-01-01

386

Gender Bias in Autoimmunity Is Influenced by Microbiota  

E-print Network

of autoimmune diseases. Gene-expression analysis suggested pathways involved in protection of males from T1D autoimmune diseases (Fish, 2008; Whitacre, 2001). In most cases, females have higher incidence andImmunity Article Gender Bias in Autoimmunity Is Influenced by Microbiota Leonid Yurkovetskiy,1

387

Genetic Analysis of Autoimmune and Metabolic Traits in Chickens  

E-print Network

of Publications 7 Abbreviations 8 Introduction 9 Background 13 Metabolic traits 13 Autoimmune diseases 13 SystemicGenetic Analysis of Autoimmune and Metabolic Traits in Chickens Weronica Ek Faculty of Veterinary Cover: Ronald Nelson, SLU #12;Genetic Analysis of Autoimmune and Metabolic Traits in Chickens Abstract

388

Integrating Autoimmune Risk Loci with Gene-Expression Data Identifies  

E-print Network

-associated genetic variants. This challenge is highlighted in autoimmune diseases, such as rheumatoid arthritis pathogenic cell types in autoimmune diseases by using a gene-expression data set of 223 murine-sorted immune and high-quality cell-type-specific gene expression is available. Introduction Autoimmune diseases

Raychaudhuri, Soumya

389

The Suppression of Immune System Disorders by Passive Sean P. Stromberg1,2  

E-print Network

The Suppression of Immune System Disorders by Passive Attrition Sean P. Stromberg1,2 *, Jean M Abstract Exposure to infectious diseases has an unexpected benefit of inhibiting autoimmune diseases the initial proliferation of autoreactive cells, thus preventing autoimmune disease. We see

Carlson, Jean

390

Increased lymphocyte Fas expression and high incidence of common variable immunodeficiency disorder in childhood Evans’ syndrome  

Microsoft Academic Search

Evans’ syndrome (ES) is characterized by autoimmune hemolytic anemia and thrombocytopenia and has been associated with immune deficiency and lymphoproliferation in some cases. Abnormalities of Fas-mediated apoptosis have been reported in various immune dysregulation disorders associated with autoimmunity and lymphoproliferation. We measured lymphocyte Fas expression and Fas-mediated T lymphocyte apoptosis in 7 children with ES, 7 with acute idiopathic thrombocytopenic

Süreyya Sava?an; Indira Warrier; Steven Buck; Joseph Kaplan; Yaddanapudi Ravindranath

2007-01-01

391

Autoimmune-induced glutamatergic receptor dysfunctions: conceptual and psychiatric practice implications.  

PubMed

Glutamatergic neurotransmission is mediated via complex receptorial systems including N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) and metabotropic receptor subtypes and plays a critical role in the modulation of synaptic plasticity, mood, cognitive processes and motor behavior. Glutamatergic function deficits are hypothesized to contribute to the pathogenesis of neuropsychiatric disorders, including schizophrenia, mood and movement disorders. Accumulating data are rapidly leading to the characterization of specific types of autoimmune encephalitis in which the receptors and proteins critically involved in glutamatergic neurotransmission, e.g., NMDA, AMPA receptors, are antigen targets. Characteristic of these syndromes, antibodies alter the structure and/or function of the corresponding neuronal antigen resulting in clinical pictures that resemble pharmacological disease models. Presently the best characterized autoimmune glutamatergic disorder is anti-NMDA receptor encephalitis. This disorder manifests with intertwined psychiatric and neurological features, defines a new syndrome, reclassifies poorly defined clinical states and extends previous hypotheses, such as hypo-NMDA receptor function in schizophrenia. The characterization of autoimmune-induced glutamatergic receptor dysfunctions (AGRD) is likely to have a substantial conceptual impact upon our understanding of neuropsychiatric disorders including schizophrenia, affective and movement dysfunctions. Further definition of AGRD will provide additional guidelines for psychiatric diagnoses, identification of homogeneous patient subtypes within broad phenomenological classifications and will contribute to the development of personalized treatments. The body of knowledge already accumulated on anti-NMDA receptor encephalitis highlights the need for wide dissemination of these concepts among psychiatrists, and in suspected cases, for early recognition, prompt clinical and laboratory investigation and efficient interface between mental health and medical teams. PMID:23791073

Rosenthal-Simons, Ayelet; Durrant, Andrea R; Heresco-Levy, Uriel

2013-12-01

392

[Autoimmune hepatitis and overlap syndrome: therapy].  

PubMed

Autoimmune Hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent acute and chronic inflammatory liver diseases in which immune reactions against host antigens are found to be the major pathological mechanism. Only for AIH there is evidence of an autoimmune etiology and humoral and cellular immune reactions are found directed against various liver cell antigens. By diverse autoantibodies several subgroups of autoimmune hepatitis can be distinguished. A very important disease promoting factor seems to be the genetically determined background for autoimmunity characterized by the HLA haplotype A1, B8 and DR3, respectively DR4. Although the histopathology of AIH shows no pathognomonic features distinguishing this type of hepatitis from virus induced chronic hepatitis there are some distinct characteristic morphological lesions. If untreated the prognosis of AIH is unfavourable but the benefit from immunosuppressive therapy with prednisolone and azathioprin is well established. In the last years there was increasing evidence for an overlap syndrome between AIH and PBC and rarely AIH and PSC. These patients are characterized by PBC characteristic bileduct lesions and oftenly antimitochondrial antibodies (AMA). They also show AIH typical inflammatory hepatic lesions in the periportal areas and portal tracts and oftenly the typical genetical background, the HLA haplotype A1, B8, DR3 or DR4. Most of these patients respond probably to a combination therapy containing prednisolon, azathioprine and ursodesoxycholic acid that leads to the reduction of the inflammatory activity. PMID:12233265

Löhr, H F

2002-08-21

393

Difficult treatment decisions in autoimmune hepatitis  

PubMed Central

Treatment decisions in autoimmune hepatitis are complicated by the diversity of its clinical presentations, uncertainties about its natural history, evolving opinions regarding treatment end points, varied nature of refractory disease, and plethora of alternative immunosuppressive agents. The goals of this article are to review the difficult treatment decisions and to provide the bases for making sound therapeutic judgments. The English literature on the treatment problems in autoimmune hepatitis were identified by Medline search up to October 2009 and 32 years of personal experience. Autoimmune hepatitis may have an acute severe presentation, mild inflammatory activity, lack autoantibodies, exhibit atypical histological changes (centrilobular zone 3 necrosis or bile duct injury), or have variant features reminiscent of another disease (overlap syndrome). Corticosteroid therapy must be instituted early, applied despite the absence of symptoms, or modified in an individualized fashion. Pursuit of normal liver tests and tissue is the ideal treatment end point, but this objective must be tempered against the risk of side effects. Relapse after treatment withdrawal requires long-term maintenance therapy, preferably with azathioprine. Treatment failure or an incomplete response warrants salvage therapy that can include conventional medications in modified dose or empirical therapies with calcineurin inhibitors or mycophenolate mofetil. Liver transplantation supersedes empirical drug therapy in decompensated patients. Elderly and pregnant patients warrant treatment modifications. Difficult treatment decisions in autoimmune hepatitis can be simplified by recognizing its diverse manifestations and individualizing treatment, pursuing realistic goals, applying appropriate salvage regimens, and identifying problematic patients early. PMID:20180231

Czaja, Albert J

2010-01-01

394

Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis  

Microsoft Academic Search

Calorie restriction (CR) prevents many age-associated diseases and prolongs the lifespan. CR induces multiple metabolic and physiologic modifications, including anti-inflammatory, antiox- idant, and neuroprotective effects that may be ben- eficial in multiple sclerosis (MS). The present stud- ies sought to determine whether CR or increased calorie intake alters the course of experimental autoimmune encephalomyelitis (EAE), the leading animal model for

Laura Piccio; Jennifer L. Stark; Anne H. Cross

2008-01-01

395

Gene therapy for autoimmune diseases: quo vadis?  

Microsoft Academic Search

Biological therapies using antibodies and cytokines are becoming widespread for the treatment of chronic inflammatory autoimmune diseases. However, these treatments have several limitations — such as expense, the need for repeated injections and unwanted side-effects — that can be overcome by genetic delivery. This review summarizes the ingenuity, sophistication and variety of gene-therapy approaches that have been taken in the

David J. Gould; Osvaldo L. Podhajcer; Yuti Chernajovsky

2004-01-01

396

Mouse Models of Experimental Autoimmune Uveitis  

Microsoft Academic Search

The mouse model of experimental autoimmune uveitis, induced by immunization of mice with the retinal protein IRBP, was developed in our laboratory 20 years ago and published in 1988. Since that time it has been adopted by many investigators and has given rise to many studies that helped elucidate genetic influences, dissect the basic mechanisms of pathogenesis and test novel

Rachel R. Caspi; Phyllis B. Silver; Dror Luger; Jun Tang; Lizette M. Cortes; Giuseppina Pennesi; Mary J. Mattapallil; Chi-Chao Chan

2008-01-01

397

Oral involvement in autoimmune bullous diseases  

Microsoft Academic Search

The oral mucosa is frequently involved by autoimmune bullous diseases and often this is the first site of manifestation. In this site the lesions are very similar, making the clinical diagnosis difficult; therefore, the definition of the immunohistopathologic characteristics of each one becomes essential for a differential diagnosis. The authors review the clinical-pathological and therapeutic aspect of these oral injuries

Marcia Ramos-e-Silva; Adriana Ferreira; Claudio de-Moura-Castro Jacques

2011-01-01

398

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

399

Metabolic Regulation in Progression to Autoimmune Diabetes  

PubMed Central

Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede ?-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes. The mechanisms behind these disturbances are unknown. Here we show the specificity of the pre-autoimmune metabolic changes, as indicated by their conservation in a murine model of type 1 diabetes. We performed a study in non-obese prediabetic (NOD) mice which recapitulated the design of the human study and derived the metabolic states from longitudinal lipidomics data. We show that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, normoglycemia, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum group. Together, the findings indicate that autoimmune diabetes is preceded by a state of increased metabolic demands on the islets resulting in elevated insulin secretion and suggest alternative metabolic related pathways as therapeutic targets to prevent diabetes. PMID:22046124

Sysi-Aho, Marko; Ermolov, Andrey; Gopalacharyulu, Peddinti V.; Tripathi, Abhishek; Seppanen-Laakso, Tuulikki; Maukonen, Johanna; Mattila, Ismo; Ruohonen, Suvi T.; Vahatalo, Laura; Yetukuri, Laxman; Harkonen, Taina; Lindfors, Erno; Nikkila, Janne; Ilonen, Jorma; Simell, Olli; Saarela, Maria; Knip, Mikael; Kaski, Samuel; Savontaus, Eriika; Oresic, Matej

2011-01-01

400

Autism and Autoimmune Disease: A Family Study  

ERIC Educational Resources Information Center

Described in a family in which the youngest boy has early infantile autism, Addison's disease, and moniliasis and two older boys have autoimmune disease with hypoparathyroidism, Addison's disease, moniliasis, and either alopecia totalis or diabetes mellitus, while the oldest boy and parents are symptom free. (KW)

Money, John; And Others

1971-01-01

401

Ultrastructural pathology of the 'barrier sites' in experimental autoimmune uveitis and experimental autoimmune pinealitis  

Microsoft Academic Search

Lewis rats were immunised with retinal S-antigen to induce experimental autoimmune uveitis and experimental autoimmune pinealitis. The blood-retinal and blood-pineal 'barrier sites' were examined by transmission electron microscopy. Inflammatory cell movement through Bruch's membrane involved separation of its constituent layers, cell migration through pores in the membrane, and between retinal pigment epithelial cells without causing significant displacement of the retinal

H. S. Dua; A. McKinnon; P. G. McMenamin; J. V. Forrester

1991-01-01

402

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

403

Imaging combined autoimmune and infectious disease microarrays  

NASA Astrophysics Data System (ADS)

Bacterial and viral pathogens are implicated in many severe autoimmune diseases, acting through such mechanisms as molecular mimicry, and superantigen activation of T-cells. For example, Helicobacter pylori, well known cause of stomach ulcers and cancers, is also identified in ischaemic heart disease (mimicry of heat shock protein 65), autoimmune pancreatitis, systemic sclerosis, autoimmune thyroiditis (HLA DRB1*0301 allele susceptibility), and Crohn's disease. Successful antibiotic eradication of H.pylori often accompanies their remission. Yet current diagnostic devices, and test-limiting cost containment, impede recognition of the linkage, delaying both diagnosis and therapeutic intervention until the chronic debilitating stage. We designed a 15 minute low cost 39 antigen microarray assay, combining autoimmune, viral and bacterial antigens1. This enables point-of-care serodiagnosis and cost-effective narrowly targeted concurrent antibiotic and monoclonal anti-T-cell and anti-cytokine immunotherapy. Arrays of 26 pathogen and 13 autoimmune antigens with IgG and IgM dilution series were printed in triplicate on epoxysilane covalent binding slides with Teflon well masks. Sera diluted 1:20 were incubated 10 minutes, washed off, anti-IgG-Cy3 (green) and anti-IgM-Dy647 (red) were incubated for 5 minutes, washed off and the slide was read in an ArrayWoRx(e) scanning CCD imager (Applied Precision, Issaquah, WA). As a preliminary model for the combined infectious disease-autoimmune diagnostic microarray we surveyed 98 unidentified, outdated sera that were discarded after Hepatitis B antibody testing. In these, significant IgG or IgM autoantibody levels were found: dsDNA 5, ssDNA 11, Ro 2, RNP 7, SSB 4, gliadin 2, thyroglobulin 13 cases. Since control sera showed no autoantibodies, the high frequency of anti-DNA and anti-thyroglobulin antibodies found in infected sera lend increased support for linkage of infection to subsequent autoimmune disease. Expansion of the antigen set with synthetic peptide sequences should reveal the shared bacterial/human epitopes involved.

Ewart, Tom; Raha, Sandeep; Kus, Dorothy; Tarnopolsky, Mark

2006-09-01

404

Antineutrophil Cytoplasmic Antibodies, Autoimmune Neutropenia, and Vasculitis  

PubMed Central

Objectives Reports of an association between antineutrophil cytoplasmic antibodies (ANCA) and autoimmune neutropenia have rarely included cases of proven vasculitis. A case of ANCA-associated vasculitis (AAV) with recurrent neutropenia is described and relevant literature on the association between ANCA, neutropenia, and vasculitis is reviewed. Methods Longitudinal clinical assessments and laboratory findings are described in a patient with AAV and recurrent episodes of profound neutropenia from December 2008 – October 2010. A PubMed database search of the medical literature was performed for papers published from 1960 through October 2010 to identify all reported cases of ANCA and neutropenia. Results A 49 year-old man developed recurrent neutropenia, periodic fevers, arthritis, biopsy-proven cutaneous vasculitis, sensorineural hearing loss, epididymitis, and positive tests for ANCA with specificity for antibodies to both proteinase 3 and myeloperoxidase. Antineutrophil membrane antibodies were detected during an acute neutropenic phase and were not detectable in a post-recovery sample, whereas ANCA titers did not seem to correlate with neutropenia. An association between ANCA and neutropenia has been reported in 74 cases from 24 studies in the context of drug/toxin exposure, underlying autoimmune disease, or chronic neutropenia without underlying autoimmune disease. In these cases, the presence of atypical ANCA patterns and other antibodies were common; however, vasculitis was uncommon and when it occurred was usually limited to the skin and in cases of underlying toxin exposure. Conclusions ANCA is associated with autoimmune neutropenia, but systemic vasculitis rarely occurs in association with ANCA and neutropenia. The interaction between neutrophils and ANCA may provide insight into understanding both autoimmune neutropenia and AAV. PMID:21507463

Grayson, Peter C.; Sloan, J. Mark; Niles, John L.; Monach, Paul A.; Merkel, Peter A.

2011-01-01

405

Autoimmune thyroid disease--a perspective.  

PubMed

Increasing evidence is accruing in favour of the view that autoimmune thyroid disease is due to an organ-specific defect in suppressor T lymphocytes that is genetically induced. While the initial evidence supporting this hypothesis was based on results with the migration inhibition factor test, subsequent investigations from our own and other laboratories have confirmed the presence of such an organ-specific suppressor T lymphocyte defect in autoimmune thyroid disease. Moreover, there is now good evidence that hyperthyroidism per se has an effect on suppressor T lymphocyte function and numbers, and this is superimposed on and is additive to the organ-specific defect while patients are hyperthyroid; this may well act as a self-perpetuating factor in continuing the disease. It has been proposed elsewhere that the expression of HLA-DR antigen on the cell membrane of the thyrocytes (possibly induced by viral infection) represents the initial inductive step in precipitating autoimmune thyroid disease in persons predisposed by virtue of having an immunoregulatory defect in the first place. However, there is now evidence that: (1) normal thyrocytes respond equally well to various stimuli in terms of DR expression when compared to Graves' or Hashimoto's thyrocytes; (2) supernatants from normal T lymphocytes will stimulate DR expression on thyrocytes at least as well as supernatants from Graves' T lymphocytes when stimulated by non-specific lectins; (3) conversely, Graves' T lymphocytes will stimulate thyroid DR expression more markedly than normal T lymphocytes when the lymphocyte-thyrocyte interaction is direct; (4) monocytes and helper T lymphocytes are essential for thyrocyte DR expression; (5) DR expression on thyrocytes does not lead to a self-perpetuating immune response. From all of these observations, it seems evident that DR expression is secondary to the primary immune assault in autoimmune thyroid disease, and is neither an initiating event, nor unique to autoimmune thyroid disease, nor a self-perpetuating phenomenon. PMID:2870410

Volpé, R

1986-02-01

406

Autoantibodies against four kinds of neurotransmitter receptors in psychiatric disorders.  

PubMed

There is a hypothesis that autoimmune abnormalities in neurotransmitter receptors might cause some psychiatric disorders. Using a sensitive radioligand assay, we detected serum autoantibodies to recombinant human muscarinic cholinergic receptor 1 (CHRM1, 34.4%), mu-opioid receptor (OPRM1, 13.1%), 5-hydroxytryptamine receptor 1A (HTR1A, 7.4%), and dopamine receptor D2 (DRD2, 4.9%) in 122 psychiatric patients. Positive antibodies to CHRM1 were found in 34.1%, 34.9%, 33.3%, and 9.1% of patients with schizophrenic disorders (n=44), mood disorders (n=63), other psychiatric disorders (n=15) and autoimmune diseases (n=33), respectively. All three patients with neuroleptic maliganant syndrome had high activities of autoantibodies to CHRM1, OPRM1, and/or HTR1A. Our data suggest that autoimmunity to neurotransmitter receptors might be associated with the induction of psychiatric symptoms and have some relation to neuroleptic malignant syndrome. PMID:12965267

Tanaka, Susumu; Matsunaga, Hidenori; Kimura, Masahiro; Tatsumi, Ke ita; Hidaka, Yoh; Takano, Toru; Uema, Takeshi; Takeda, Masatoshi; Amino, Nobuyuki

2003-08-01

407

Diagnosing and Treating the Predominantly Female Problems of Systemic Autoimmune Diseases.  

PubMed

Autoimmune diseases with rheumatic manifestations are predominantly diseases of women. Any woman with new onset arthralgia or arthritis should have a thorough history and physical to rule out autoimmune connective-tissue disease. Screening serologic tests, however, are not necessarily recommended because of high false-positive rates. Serologic tests are most useful in confirming or ruling out the diagnosis; for example, systemic lupus erythematosus (SLE) is rarely present when antinuclear antibodies (ANAs) are absent; the absence of rheumatoid factor will not rule out rheumatoid arthritis (RA), but its presence confirms it. Most autoantibodies (RF [rheumatoid factor], ANA, ENA [extractable nuclear antigen], anti-Jo-1, etc) do not vary with disease flare-ups and remissions. Plain radiographs of the joints are not useful except as a baseline and in detecting erosion at end of long bones associated with RA. Polymyalgia rheumatica and RA, with an incidence of 1 in 2000 to 3000, are the most common autoimmune disorders. Other autoimmune diseases such as SLE, vasculitis, polymyositis, and dermatomyositis are seen infrequently in general practice. Pregnancy, menopause, or breast implantation may affect disease prognosis and treatment. For example, in pregnancy, RA symptoms generally improve, whereas those of SLE may worsen; both diseases may flare postpartum. Oral contraceptives have been associated with an increase in disease flare-ups, but there is little or no evidence that estrogen in the dose level used for replacement is harmful to SLE patients. Although relatively rare, autoimmune diseases can be devastating to the patient if not promptly recognized and properly treated. PMID:9746680

Davidson; Keiser

1997-02-01

408

Management of thyroid disorders  

PubMed Central

Autoimmune thyroid disease is the predominant form of thyroid dysfunction in the developed world. Although its precise cause is currently unclear, principles of management have been established. There is a vigorous debate about the management of the increasingly commonly recognised subclinical forms of thyroid dysfunction despite recent recommendations. Nodular thyroid disease and thyroid carcinoma have received wide attention. The effects of drugs and pregnancy on thyroid function have also been investigated widely. This short review attempts to give an overview and clarify the current management of common thyroid disorders. PMID:16954449

Premawardhana, L D K E; Lazarus, J H

2006-01-01

409

Glycine Receptor Autoimmune Spectrum With Stiff-Man Syndrome Phenotype  

PubMed Central

Objectives To determine whether glycine receptor ?1 subunit-specific autoantibodies (GlyR?1-IgG) occur in a broader spectrum of brainstem and spinal hyperexcitability disorders than the progressive encephalomyelitis with rigidity and myoclonus phenotype recognized to date, and to ascertain disease specificity. Design Retrospective, case-control study. Settings Mayo Clinic, Rochester, Minnesota, and University of Barcelona, Spain. Patients Eighty-one patients with stiff-man syndrome phenotype, 80 neurologic control subjects, and 20 healthy control subjects. Intervention Glycine receptor ?1–transfected cells to test serum or cerebrospinal fluid from cases and control subjects. Main Outcome Measures Frequency of GlyR?1-IgG positivity among stiff-man syndrome phenotype cases and control subjects. Comparison of GlyR?1-IgG seropositive and seronegative cases. Results Seropositive cases (12% of cases) included 9 with stiff-man syndrome (4 classic; 5 variant; 66% were glutamic acid decarboxylase 65–IgG positive) and 1 with progressive encephalomyelitis with rigidity and myoclonus. Immunotherapy responses were noted more frequently in GlyR?1-IgG–positive cases (6 of 7 improved) than in seronegative cases (7 of 25 improved; P=.02). The single seropositive control patient had steroid-responsive vision loss and optic atrophy with inflammatory cerebrospinal fluid. Conclusions Glycine receptor ?1–IgG aids identification of autoimmune brainstem/spinal cord hyperexcitability disorders and may extend to the glycinergic visual system. PMID:23090334

McKeon, Andrew; Martinez-Hernandez, Eugenia; Lancaster, Eric; Matsumoto, Joseph Y.; Harvey, Robert J.; McEvoy, Kathleen M.; Pittock, Sean J.; Lennon, Vanda A.; Dalmau, Josep

2013-01-01

410

Myasthenia and related disorders of the neuromuscular junction  

Microsoft Academic Search

Our understanding of transmission at the neuromuscular junction has increased greatly in recent years. We now recognise a wide variety of autoimmune and genetic diseases that affect this specialised synapse, causing muscle weakness and fatigue. These disorders greatly affect quality of life and rarely can be fatal. Myasthenia gravis is the most common disorder and is most commonly caused by

Jennifer Spillane; David J Beeson; Dimitri M Kullmann

2010-01-01

411

Inflammatory Disorders of the Skin  

Microsoft Academic Search

\\u000a Inflammatory disorders of the skin, including eczematous, psoriasiform, lichenoid-interface, ­autoimmune, and neutrophilic\\u000a dermatoses, probably represent the group of cutaneous diseases in which molecular pathology currently has the least impact\\u000a in daily clinical practice. Many of these diseases are readily diagnosed through the correlation of clinical features with\\u000a histopathological findings on hematoxylin and eosin (H + E)-stained tissue sections. In general,

Michael J. Murphy; Amanda Phelps; Markus Braun-Falco

412

Recent insights into the role of the PD-1/PD-L1 pathway in immunological tolerance and autoimmunity.  

PubMed

Autoimmune diseases represent a heterogeneous group of conditions whose incidence is increasing worldwide. This has stimulated studies on their etiopathogenesis, derived from a complex interaction between genetic and environmental factors, in order to improve prevention and treatment of these disorders. The relevance of T regulatory cells and of the PD-1/PD-L1 pathway in controlling immune responses has been highlighted. Recent studies have in particular elucidated the putative role of the PD-1/PD-L1 pathway in regulating T cell responses and its effects on immunological tolerance and immune-mediated tissue damage. The role of the PD-1/PD-L1 pathway in autoimmunity has been already investigated in vivo in several experimental animal models including insulin-dependent diabetes mellitus, systemic lupus erythematosus, myocarditis, encephalomyelitis, rheumatoid arthritis and inflammatory bowel diseases. With the advent of candidate gene and genome-wide association studies, single nucleotide polymorphisms (SNPs) in PD-1 gene in humans have demonstrated relevant associations with a higher risk of developing autoimmune diseases in certain ethnic groups. In this review we present recent insights into the role of the PD-1/PD-L1 pathway in regulating lymphocyte activation, promotion of T regulatory cell development and function, breakdown of tolerance and development of autoimmunity. We finally speculate on the possible development of novel therapeutic treatments in human autoimmunity by modulating the PD-1/PD-L1 pathway. PMID:23792703

Gianchecchi, Elena; Delfino, Domenico Vittorio; Fierabracci, Alessandra

2013-09-01

413

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

414

Type-2 diabetes and coronary heart disease: common physiopathology, viewed from autoimmunity.  

PubMed

Two highly prevalent diseases, Type-2 diabetes mellitus and coronary heart disease (CHD), share risk factors. Excess levels of LDL-cholesterol have been overemphasized to uniformly encompass the development of CHD, and the origin of insulin resistance underlying Type-2 diabetes has not been fully elucidated. Autoimmune response has been recognized to be responsible only of a small minority of diabetes. The increasing trend in the worldwide prevalence of diabetes and the risk factors for both diseases are reviewed, the independent mediation for CHD of (central) adiposity in both diseases and the 'hypertriglyceridemic waist' phenotype are outlined. Evidence is described that serum lipoprotein (Lp)(a) concentrations, not only in excess, but also in apparently 'reduced' levels, as a result of autoimmune response, underlie both disorders and are closely related to insulin resistance. PMID:24846677

Onat, Altan; Dönmez, Ibrahim; Karadeniz, Yusuf; Cak?r, Hakan; Kaya, Ay?em

2014-06-01

415

AUTOIMMUNE STIFF PERSON SYNDROME AND RELATED MYELOPATHIES: UNDERSTANDING OF ELECTROPHYSIOLOGICAL AND IMMUNOLOGICAL PROCESSES  

PubMed Central

Stiff Person Syndrome (SPS) is a disabling autoimmune CNS disorder characterized by progressive muscle rigidity and gait impairment with superimposed painful spasms that involve axial and limb musculature, triggered by heightened sensitivity to external stimuli. Impaired synaptic GABAergic inhibition resulting from intrathecal B-cell-mediated clonal synthesis of autoantibodies against various presynaptic and synaptic proteins in the inhibitory neurons of the brain and spinal cord is believed to be an underlying pathogenic mechanism. SPS is most often idiopathic, but it can occur as a paraneoplastic condition. Despite evidence that anti-GAD and related autoantibodies impair GABA synthesis, the exact pathogenic mechanism of SPS is not fully elucidated. The strong association with several MHC-II alleles and improvement of symptoms with immune-modulating therapies support an autoimmune etiology of SPS. In this review, we discuss the clinical spectrum, neurophysiological mechanisms, and therapeutic options, including a rationale for agents that modulate B cell function in SPS. PMID:22499087

Rakocevic, Goran; Floeter, Mary Kay

2011-01-01

416

Obesity as a Risk and Severity Factor in Rheumatic Diseases (Autoimmune Chronic Inflammatory Diseases)  

PubMed Central

The growing body of evidence recognizing the adipose tissue (AT) as an active endocrine organ secreting bioactive mediators involved in metabolic and inflammatory disorders, together with the global epidemic of overweight and obesity, rise obesity as a hot topic of current research. The chronic state of low-grade inflammation present in the obese condition and the multiple pleiotropic effects of adipokines on the immune system has been implicated in the pathogenesis of several inflammatory conditions including rheumatic autoimmune and inflammatory diseases. We will discuss the main relevant evidences on the role of the AT on immune and inflammatory networks and the more recent evidences regarding the effects of obesity on the incidence and outcomes of the major autoimmune chronic inflammatory diseases.

Gremese, Elisa; Tolusso, Barbara; Gigante, Maria Rita; Ferraccioli, Gianfranco

2014-01-01

417

Role of oxidative stress and autoimmunity in onset and progression of vitiligo.  

PubMed

Vitiligo is an acquired depigmentation disorder characterized by the loss of functional melanocytes from the epidermis. Two major theories of vitiligo pathogenesis include autoimmunity and oxidative stress-mediated toxicity in melanocytes. The present study aimed to evaluate both the hypotheses in vitiligo patients and to investigate their role in the disease onset and progression. Antimelanocyte antibody levels and lipid peroxidation (LPO) levels were evaluated in 427 patients and 440 controls; antithyroid peroxidase (TPO) antibody levels were estimated in 102 patients and 72 controls. Patients showed a significant increase in LPO and antimelanocyte antibody levels compared to controls. Antimelanocyte antibody and LPO levels were higher in active vitiligo compared to stable. Only 9.8% of patients showed the presence of anti-TPO antibodies in their circulation. Oxidative stress may be the initial triggering event to precipitate vitiligo in Gujarat population, which is exacerbated by contributing autoimmune factors together with oxidative stress. PMID:24628992

Laddha, Naresh C; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Singh, Mala; Gani, Amina R; Yeola, Asmita P; Panchal, Vipul N; Khan, Fazal; Dave, Darshana J; Patel, Ananddeep; Madhavan, Shajil E; Gupta, Richa; Marfatia, Zarna; Marfatia, Yogesh S; Begum, Rasheedunnisa

2014-05-01

418

Mental Disorders  

MedlinePLUS

Mental disorders include a wide range of problems, including Anxiety disorders, including panic disorder, obsessive-compulsive disorder, post- ... disorders, including schizophrenia There are many causes of mental disorders. Your genes and family history may play a ...

419

Diagnosis and classification of autoimmune diabetes mellitus.  

PubMed

Diabetes mellitus is increasing in prevalence worldwide. The economic costs and burden of the disease are considerable given the cardiovascular complications and co-morbidities that it may entail. Two major groups of diabetes mellitus have been defined, type 1, or immune-based, and type 2. In recent years, other subgroups have been described in-between these major groups. Correct classification of the disease is crucial in order to ascribe the most efficient preventive, diagnostic and treatment strategies for each patient. In the present review, we discuss the epidemiology, etiopathogenesis, diagnostic criteria and clinical classification of what is currently known as autoimmune diabetes. In addition, the other groups of diabetes mellitus will be regarded in relation to their pathogenesis and potential autoimmunity features. PMID:24424179

Canivell, Silvia; Gomis, Ramon

2014-01-01

420

Autoimmunity vs. cancer: predator vs. alien?  

PubMed

"The enemy of my enemy is my friend." According to this motto, the human protagonists in Paul W. S. Anderson's science-fiction movie "Alien vs. Predator" (2004) solidarize with a predator in order to fight the aliens. Can this ancient and simple logic be transferred to the field of oncology and cancer immunotherapy? Can we utilize mechanisms known from the context of autoimmunity to fight cancer? Here, we summarize immune cell-mediated detection of danger and damage, central and peripheral tolerance, immunoregulation and immune privilege--processes known to be deregulated in the context of autoimmunity. We discuss them with special regard towards their misusage by tumors and pathogens and how they might be instrumentalized in the context of anti-cancer immunotherapy. PMID:23706137

Berens, Christian; Lauber, Kirsten; Herrmann, Martin

2013-08-01

421

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

422

MRI of insulitis in autoimmune diabetes.  

PubMed

Development of imaging techniques that would allow the mapping of immune cells in vivo could greatly aid our understanding of a number of inflammatory and autoimmune diseases. The current study focused on imaging of autoimmune destruction of the insulin-producing pancreatic beta-cells by cytotoxic lymphocytes, the cause of insulin-dependent diabetes mellitus (IDDM; Type 1 diabetes). Using high-resolution MR microscopy and a conventional clinical MR imaging system, it was possible to visualize the infiltration of immune cells in the diabetic mouse pancreas. Mouse lymphocytes were visualized by magnetically labeling them with recently developed magnetic nanoparticles (CLIO-Tat). The results from this study could potentially lead to detection of immune infiltration during diabetes formation in vivo, which would be one of the earliest parameters of disease development. PMID:11948737

Moore, Anna; Sun, Phillip Zhe; Cory, David; Högemann, Dagmar; Weissleder, Ralph; Lipes, Myra A

2002-04-01

423

Friendly pathogens: prevent or provoke autoimmunity.  

PubMed

The gut microflora is an immense health asset for human beings. The mammalian gut harbors trillions of commensals. These microbes not only modulate local but also systemic immunity. Recently, various reports are evolving, which signify that the gut microbes can modulate, tune and tame the host immune response. Consequently, it advocates the significance of the microbial composition. Further, the microbiota provides a fine equilibrium to host by regulating immune homeostasis. Furthermore, disturbance in this population can incite imbalance in immune system, leading to molecular mimicry and therefore autoimmunity. Hence, it is imperative to understand the influence of these bugs in preventing or provoking immune system against the self-components. In this article, we highlight the interaction between different gut microbes and cells of immune system and the mechanism involved in controlling and curtailing various autoimmune diseases. PMID:23688247

Sathyabama, Sathyaseelan; Khan, Nargis; Agrewala, Javed N

2014-08-01

424

Autoimmune progesterone dermatitis: a case report.  

PubMed

Background. Autoimmune progesterone dermatitis is a rare cyclic premenstrual allergic reaction to progesterone produced during the luteal phase of a woman's menstrual cycle. Patients present with a variety of conditions including erythema multiforme, eczema, urticaria, angioedema, and progesterone-induced anaphylaxis. Case. Thirty-eight-year-old woman G2P2002 presents with erythema multiforme and urticarial rash one week prior to her menses starting one year after menarche. She was treated with oral contraceptive pills and the symptoms resolved. Conclusion. This is a typical case of progesterone autoimmunity. The diagnosis is based on cyclic nature of the dermatitis. This differentiates the condition from other allergies or systemic diseases with skin manifestations. Inhibition of ovulation in such cases results in decrease in progesterone secretion and prevention of symptoms. PMID:22924142

George, Rachana; Badawy, Shawky Z A

2012-01-01

425

Role of Microglia in CNS Autoimmunity  

PubMed Central

Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS) in the Western world. The disease is characterized histologically by the infiltration of encephalitogenic TH1/TH17-polarized CD4+ T cells, B cells, and a plethora of myeloid cells, resulting in severe demyelination ultimately leading to a degeneration of neuronal structures. These pathological processes are substantially modulated by microglia, the resident immune competent cells of the CNS. In this overview, we summarize the current knowledge regarding the highly diverse and complex function of microglia during CNS autoimmunity in either promoting tissue injury or tissue repair. Hence, understanding microglia involvement in MS offers new exciting paths for therapeutic intervention. PMID:23840238

Prinz, Marco

2013-01-01

426

Osteopontin Is Proinflammatory in Experimental Autoimmune Uveitis  

Microsoft Academic Search

PURPOSE. Osteopontin (OPN) has been implicated in inflamma- tory and wound-healing processes. Increased OPN mRNA lev- els have been reported in experimental autoimmune uveitis (EAU), but the function of OPN in the inflamed eye is un- known. The purpose of this study was to investigate the role of OPN in the pathogenesis of EAU. METHODS. EAU was induced in OPN-null

Sherry T. Hikita; Barbara P. Vistica; Heather R. Jones; Jennifer R. Keswani; Morgan M. Watson; Vivian R. Ericson; George S. Ayoub; Igal Gery; Dennis O. Clegg

2006-01-01

427

Natural regulatory T cells in autoimmunity  

PubMed Central

The suppressive/immunomodulatory function of CD4+CD25+Foxp+ regulatory T (Treg) cells is crucial for the maintenance of immune homeostasis, which helps to prevent autoimmunity and reduce the inflammation induced by pathogens and environmental insults. This review summarizes the current knowledge on the types and mechanisms of action of Treg cells and their role in the immune tolerance to self antigens, with a particular focus on naturally occurring Treg cells. PMID:21091291

Lourenco, Elaine V.; La Cava, Antonio

2010-01-01

428

Empty sella and primary autoimmune hypothyroidism  

Microsoft Academic Search

In order to assess the association between empty sella (ES) and primary autoimmune hypothyroidism, and the possibility of\\u000a a common pathogenesis. We retrospectively studied all patients with presumed ES diagnosed in the last 20 years, most of whom\\u000a were treated by our Endocrinology Department. Subjects with a known etiology were excluded. Incomplete records or those with\\u000a a doubtful diagnosis were also

Rogelio García-Centeno; José Pablo Suárez-Llanos; Elisa Fernández-Fernández; Victor Andía-Melero; Petra Sánchez; Antonino Jara-Albarrán

2010-01-01

429

GM-CSF in inflammation and autoimmunity  

Microsoft Academic Search

Granulocyte macrophage-colony stimulating factor (GM-CSF) is now best viewed as a major regulator governing the functions of granulocyte and macrophage lineage populations at all stages of maturation. There is recent evidence for a key role for GM-CSF in inflammatory and autoimmune diseases, therefore making it worthy of consideration for targetting. Such evidence includes disease exacerbation following its administration and amelioration

John A Hamilton

2002-01-01

430

Experimental Autoimmune Encephalomyelitis in the Mouse  

PubMed Central

This unit details the materials and methods required for both active induction and adoptive transfer of experimental autoimmune encephalomyelitis (EAE) in the SJL mouse strain using intact proteins or peptides from the two major myelin proteins: proteolipid protein (PLP) and myelin basic protein (MBP). Detailed materials and methods required for the purification of both PLP and MBP are also described. Modifications of the specified protocols may be necessary for efficient induction of active or adoptive EAE in other mouse strains. PMID:18432984

Miller, Stephen D.; Karpus, William J.; Davidson, Todd Scott

2010-01-01

431