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Sample records for adult autoimmune enteropathy

  1. Glutamine-Supplemented Parenteral Nutrition and Probiotics in Four Adult Autoimmune Enteropathy Patients

    PubMed Central

    Xu, Ren-Ying; Zhou, Yi-Quan; Lu, Li-Ping; Chen, Zhi-Qi; Wu, Ying-Jie; Cai, Wei

    2014-01-01

    To evaluate the effects of glutamine-supplemented parenteral nutrition (PN) and probiotics in adult autoimmune enteropathy (AIE) patients. Four adult AIE patients were identified from April 2006 to January 2012. Clinical and nutritional data were obtained from the patients' medical records. Glutamine-supplemented PN started immediately when the AIE diagnosis was confirmed. The total PN duration was 351 days. According to the PN prescription, the average caloric intake ranged from 20 to 25 kcal/kg/day, and the protein intake ranged from 1.2 to 1.5 g/kg/day. Alanyl-glutamine (20 g/day) was administered to AIE patients for 4 weeks followed by a 2-week break, and this treatment schedule was repeated when PN lasted for more than 6 weeks. Body weight gain and an increased serum albumin level were achieved after PN, and defecation frequency and quality also improved. Each patient received oral supplements, 250 mL of Ensure and two probiotics capsules (each capsule containing 0.5×108 colonies) three times a day when enteral nutrition started. Three AIE patients were successfully weaned off PN, and one patient died of pneumonia. Glutamine-supplemented PN and probiotics show promise in managing patients with AIE and related malnutrition. PMID:24827631

  2. Diffuse Autoimmune Enteropathy and Colopathy in an Adult Patient Successfully Treated With Adalimumab and a Review of the Literature.

    PubMed

    Hasan, Syed Shafae; Siddiqui, Nauman Saleem; Chaitanya Arudra, Sri Krishna; de Las Casas, Luis; Akpunonu, Basil; Nawras, Ali

    2016-01-01

    Autoimmune enteropathy (AIE) is a rare disease that causes intractable diarrhea not responsive to a gluten free diet and must be distinguished from refractory sprue. It is associated with circulating autoantibodies against goblet cells and enterocytes. AIE mainly involves the small intestines, with very few cases reported in adults. Because of the paucity of cases, the epidemiology of the disease remains unclear, and treatment is based on the cases found in the literature. Of the 35 adult cases reported, only 4 involved the colon. Because of the low number of cases, there have been no clear recommendations on treatment modalities with most reports heavily emphasizing steroids as the mainstay of treatment. We present the case of adult female patient who developed postpartum AIE and colopathy with profuse diarrhea successfully treated with adalimumab and a review of the literature. To the best of our knowledge, this case is only the fourth case of a tumor necrosis factor alpha antagonist being used in the treatment of AIE and the first case of adalimumab being used. PMID:25379737

  3. A Difficult and Rare Diagnosis of Autoimmune Enteropathy in a Patient Affected by Down Syndrome.

    PubMed

    Depince-Berger, Anne; Cremilieux, Clara; Rinaudo-Gaujous, Melanie; Genin, Christian; de Freminville, Benedicte; Lambert, Claude; Bruneau, J; Paul, Stephane

    2016-07-01

    Patients with Down syndrome are more susceptible to autoimmune pathologies, in particular endocrine or digestive diseases such as celiac disease. Autoimmune enteropathy is another form of digestive autoimmune disease, non-gluten-dependant, more often diagnosed in male neonates with immunodysregulation and polyendocrinopathy such as the Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome. It also exists in the adult, but this pathology is less known and therefore frequently under-diagnosed. Clinical manifestations are similar to celiac disease, but not improved after a gluten-free diet. Autoimmune enteropathy is frequently associated with other autoimmune diseases, such as thyroiditis, myasthenia gravis, lupus or immune deficiencies, as Common Variable Immunodeficiency. Pathological analysis of intestinal biopsies can frequently distinguish autoimmune enteropathy and celiac disease. Autoimmune enteropathy usually has an important lymphoplasmacytic infiltration of the mucosa and a lack of intraepithelial lymphocytes in the gastrointestinal mucosal surface, while celiac disease usually has a polymorph infiltration of the mucosa and an important intraepithelial lymphocytes infiltration. Nevertheless, the two pathological patterns may overlap. Here we report the first case of a patient with Down syndrome associated to autoimmune enteropathy (initially diagnosed as celiac disease), chronic pancreatitis and cutaneous lupus erythematosus. Even if autoimmune pathologies are much more common in patients with Down syndrome, we would like to report on this rare and original association found in our patient. PMID:27072857

  4. Autoimmune enteropathy: not all flat mucosa mean coeliac disease

    PubMed Central

    Volta, Umberto; Mumolo, Maria Gloria; Caio, Giacomo; Boschetti, Elisa; Latorre, Rocco; Giancola, Fiorella; Paterini, Paola; Giorgio, Roberto De

    2016-01-01

    A 62-year-old woman complaining of severe malabsorption was diagnosed with celiac disease based on the findings of flat, small intestinal mucosa and HLA-DQ2 positivity, although celiac serology was negative. This diagnosis was questioned due to the lack of clinical and histological improvement after a long period of strict gluten-free diet. The detection of enterocyte autoantibodies guided to the correct diagnosis of autoimmune enteropathy, leading to a complete recovery of the patient following an appropriate immunosuppressive treatment. Autoimmune enteropathy should be considered in the differential diagnosis of malabsorption with severe villous atrophy, including those cases with negative celiac-related serology. PMID:27099674

  5. Shwachman-Diamond syndrome with autoimmune-like liver disease and enteropathy mimicking celiac disease.

    PubMed

    Veropalumbo, Claudio; Campanozzi, Angelo; De Gregorio, Fabiola; Correra, Antonio; Raia, Valeria; Vajro, Pietro

    2015-02-01

    Liver abnormalities that normalize during infancy as well an enteropathy are reported in Shwachman-Diamond syndrome (SDS). The pathogenesis of both conditions is unknown. We report two SDS cases with autoimmune-like (antismooth muscle and/or antinuclear antibody positivity) liver disease and antigliadin antibody positive inflammatory enteropathy. Hypertransaminasemia did not resolve after immunosuppressive therapy and/or a gluten-free diet. These transient autoimmune phenomena and gut-liver axis perturbations may have played a role in transient SDS hepatopathy and enteropathy. Our report may stimulate other studies to define the relationship between the SDS genetic defect and intestinal permeability as the pathogenic mechanism underlying SDS related liver and intestinal inflammation. PMID:25129842

  6. High dose multiple micronutrient supplementation improves villous morphology in environmental enteropathy without HIV enteropathy: results from a double-blind randomised placebo controlled trial in Zambian adults

    PubMed Central

    2014-01-01

    Background Environmental enteropathy (EE) is an asymptomatic abnormality of small bowel structure and function, which may underlie vaccine inefficacy in the developing world. HIV infection co-exists in many of these populations. There is currently no effective treatment. We conducted a secondary analysis of a randomised controlled trial of high dose multiple micronutrient (MM) supplementation on small bowel architecture in EE in participants with or without HIV infection. Methods In a double-blind parallel-group trial of the effect of MM on innate immune responses to oral vaccines, consenting Zambian adults were randomised to receive 6 weeks of 24 micronutrients as a daily capsule or placebo. HIV status was established after randomisation. Proximal jejunal biopsies were obtained after the supplementation period. Villous height, crypt depth, villous width, villous perimeter per 100 μm muscularis mucosa (a measure of epithelial surface area), and villous cross sectional area per 100 μm muscularis mucosa (a measure of villous compartment volume) were measured in orientated biopsy sections using semi-automated image analysis. Analysis was by intention to treat. Results 18 patients received MM and 20 placebo. 6/18 MM and 9/20 placebo patients had HIV. In HIV negative patients given MM compared to placebo, mean villous height was 24.0% greater (293.3 v. 236.6 μm; 95% CI of difference 17.7–95.9 μm; P = 0.006), mean villous area was 27.6% greater (27623 v. 21650 μm2/100 μm; 95% CI of difference 818–11130 μm2/100 μm; P = 0.03), and median villous perimeter was 29.7% greater (355.0 v. 273.7 μm/100 μm; 95% CI of difference 16.3–146.2 μm/100 μm; P = 0.003). There was no significant effect on crypt depth or villous width. No effect was observed in HIV positive patients. There were no adverse events attributable to MM. Conclusions MM improved small bowel villous height and absorptive area, but not crypt depth, in adults with EE without HIV. Nutritional

  7. [Primary immunodeficiencies presenting with autoimmune cytopenias in adults].

    PubMed

    Sève, P; Broussolle, C; Pavic, M

    2013-03-01

    Although primary immunodeficiencies (PID) are typically marked by increased susceptibility to infections, autoimmune manifestations have increasingly been recognized as an important component of several forms of PID. Here, we discuss two forms of PID in which autoimmune cytopenias are particularly common and may be the first manifestation of the disease in adults: autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency (CVID). Approximately one fifth of patients with CVID develop autoimmune diseases, and immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AHA) are the most common. Since autoimmune cytopenias frequently precede the diagnosis of CVID, testing for immunoglobulin levels should be performed in patients diagnosed with AITP and AHA. Patients with CVID in association with autoimmune cytopenias have a "particular phenotype" with lower susceptibility to infection and higher susceptibility to autoimmune manifestations and, for patients with AHA, a more frequent development of splenomegaly and lymphoma. Corticosteroids and high doses of intravenous immunoglobulins (IVIg) seem to have the same efficacy as in idiopathic AITP and AHA. Splenectomy and rituximab are as effective as in idiopathic autoimmune cytopenias but are associated with an increased risk of severe infection and should, in our opinion, be considered only for those rare patients with "refractory diseases". The course and outcome of autoimmune cytopenias is not affected by supportive IVIg therapy. Autoimmune destruction of blood cells affects over 70% of ALPS patients. The median age of first presentation is 24 months of age, but with increasing awareness of this condition, adults with autoimmune cytopenias are now being diagnosed more frequently. Testing for ALPS should therefore be considered in young adults with unexplained Evan's syndrome. Patients usually respond to immunosuppressive medications, including corticosteroids. Unlike many patients

  8. Protein-losing enteropathy

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/007338.htm Protein-losing enteropathy To use the sharing features on this page, please enable JavaScript. Protein-losing enteropathy is an abnormal loss of protein ...

  9. Latent autoimmune diabetes of the adult: current knowledge and uncertainty

    PubMed Central

    Laugesen, E; Østergaard, J A; Leslie, R D G

    2015-01-01

    Patients with adult-onset autoimmune diabetes have less Human Leucocyte Antigen (HLA)-associated genetic risk and fewer diabetes-associated autoantibodies compared with patients with childhood-onset Type 1 diabetes. Metabolic changes at diagnosis reflect a broad clinical phenotype ranging from diabetic ketoacidosis to mild non-insulin-requiring diabetes, also known as latent autoimmune diabetes of the adult (LADA). This latter phenotype is the most prevalent form of adult-onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. Although LADA is associated with the same genetic and immunological features as childhood-onset Type 1 diabetes, it also shares some genetic features with Type 2 diabetes, which raises the question of genetic heterogeneity predisposing to this form of the disease. The potential value of screening patients with adult-onset diabetes for diabetes-associated autoantibodies to identify those with LADA is emphasized by their lack of clinically distinct features, their different natural history compared with Type 2 diabetes and their potential need for a dedicated management strategy. The fact that, in some studies, patients with LADA show worse glucose control than patients with Type 2 diabetes, highlights the need for further therapeutic studies. Challenges regarding classification, epidemiology, genetics, metabolism, immunology, clinical presentation and treatment of LADA were discussed at a 2014 workshop arranged by the Danish Diabetes Academy. The presentations and discussions are summarized in this review, which sets out the current ideas and controversies surrounding this form of diabetes. What’s new? Latent autoimmune diabetes of the adult (LADA) is an autoimmune diabetes defined by adult-onset, presence of diabetes associated autoantibodies, and no insulin treatment requirement for a period after diagnosis. Immunologically, glutamic acid decarboxylase 65 autoantibodies are by far the most

  10. PRENATAL TCDD IN MICE INCREASES ADULT AUTOIMMUNITY

    PubMed Central

    Holladay, Steven D.; Gogal, Robert M.

    2010-01-01

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

  11. Cumulative Childhood Stress and Autoimmune Diseases in Adults

    PubMed Central

    Dube, Shanta R.; Fairweather, DeLisa; Pearson, William S.; Felitti, Vincent J.; Anda, Robert F.; Croft, Janet B.

    2012-01-01

    Objective To examine whether childhood traumatic stress increased the risk of developing autoimmune diseases as an adult. Methods Retrospective cohort study of 15,357 adult health maintenance organization members enrolled in the Adverse Childhood Experiences (ACEs) Study from 1995 to 1997 in San Diego, California, and eligible for follow-up through 2005. ACEs included childhood physical, emotional, or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental divorce, and/or an incarcerated household member. The total number of ACEs (ACE Score range = 0–8) was used as a measure of cumulative childhood stress. The outcome was hospitalizations for any of 21 selected autoimmune diseases and 4 immunopathology groupings: T- helper 1 (Th1) (e.g., idiopathic myocarditis); T-helper 2 (Th2) (e.g., myasthenia gravis); Th2 rheumatic (e.g., rheumatoid arthritis); and mixed Th1/Th2 (e.g., autoimmune hemolytic anemia). Results Sixty-four percent reported at least one ACE. The event rate (per 10,000 person-years) for a first hospitalization with any autoimmune disease was 31.4 in women and 34.4 in men. First hospitalizations for any autoimmune disease increased with increasing number of ACEs (p < .05). Compared with persons with no ACEs, persons with ≥2 ACEs were at a 70% increased risk for hospitalizations with Th1, 80% increased risk for Th2, and 100% increased risk for rheumatic diseases (p < .05). Conclusions Childhood traumatic stress increased the likelihood of hospitalization with a diagnosed autoimmune disease decades into adulthood. These findings are consistent with recent biological studies on the impact of early life stress on subsequent inflammatory responses. PMID:19188532

  12. Latent autoimmune diabetes of the adult: current knowledge and uncertainty.

    PubMed

    Laugesen, E; Østergaard, J A; Leslie, R D G

    2015-07-01

    Patients with adult-onset autoimmune diabetes have less Human Leucocyte Antigen (HLA)-associated genetic risk and fewer diabetes-associated autoantibodies compared with patients with childhood-onset Type 1 diabetes. Metabolic changes at diagnosis reflect a broad clinical phenotype ranging from diabetic ketoacidosis to mild non-insulin-requiring diabetes, also known as latent autoimmune diabetes of the adult (LADA). This latter phenotype is the most prevalent form of adult-onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. Although LADA is associated with the same genetic and immunological features as childhood-onset Type 1 diabetes, it also shares some genetic features with Type 2 diabetes, which raises the question of genetic heterogeneity predisposing to this form of the disease. The potential value of screening patients with adult-onset diabetes for diabetes-associated autoantibodies to identify those with LADA is emphasized by their lack of clinically distinct features, their different natural history compared with Type 2 diabetes and their potential need for a dedicated management strategy. The fact that, in some studies, patients with LADA show worse glucose control than patients with Type 2 diabetes, highlights the need for further therapeutic studies. Challenges regarding classification, epidemiology, genetics, metabolism, immunology, clinical presentation and treatment of LADA were discussed at a 2014 workshop arranged by the Danish Diabetes Academy. The presentations and discussions are summarized in this review, which sets out the current ideas and controversies surrounding this form of diabetes. PMID:25601320

  13. [Protein-losing enteropathy].

    PubMed

    Amiot, A

    2015-07-01

    Protein-losing enteropathy is a rare syndrome of gastrointestinal protein loss. The primary causes can be classified into lymphatic leakage due to increased interstitial pressure and increased leakage of protein-rich fluids due to erosive or non-erosive gastrointestinal disorders. The diagnosis of protein-losing enteropathy should be considered in patients with chronic diarrhea and peripheral oedema. The diagnosis of protein-losing enteropathy is most commonly based on the determination of fecal alpha-1 antitrypsin clearance. Most protein-losing enteropathy cases are the result of either lymphatic obstruction or a variety of gastrointestinal disorders and cardiac diseases, while primary intestinal lymphangiectasia (Waldmann's disease) is less common. Treatment of protein-losing enteropathy targets the underlying disease but also includes dietary modification, such as high-protein and low-fat diet along with medium-chain triglyceride supplementation. PMID:25618488

  14. Coeliac disease in endocrine diseases of autoimmune origin.

    PubMed

    Miśkiewicz, Piotr; Kępczyńska-Nyk, Anna; Bednarczuk, Tomasz

    2012-01-01

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

  15. Should There be Concern About Autoimmune Diabetes in Adults? Current Evidence and Controversies.

    PubMed

    Østergaard, Jakob Appel; Laugesen, Esben; Leslie, R David

    2016-09-01

    Autoimmune diabetes has a heterogeneous phenotype. Although often considered a condition starting in childhood, a substantial proportion of type 1 diabetes presents in adult life. This holds important implications for our understanding of the factors that modify the rate of progression through the disease prodrome to clinical diabetes and for our management of the disease. When autoimmune diabetes develops in adulthood, insulin treatment is often not required at the time of diagnosis, and this autoimmune non-insulin requiring diabetes is generally termed latent autoimmune diabetes in adults (LADA). Patients with LADA are generally leaner, younger at diabetes onset; have a greater reduction in C-peptide; and have a greater likelihood of insulin treatment as compared with patients with type 2 diabetes. The LADA subset of patients with adult-onset autoimmune diabetes has highlighted many shortcomings in the classification of diabetes and invokes the case for more personalized data analysis in line with the move towards precision medicine. Perhaps most importantly, the issues highlight our persistent failure to engage with the heterogeneity within the most common form of autoimmune diabetes, that is adult-onset type 1 diabetes, both insulin-dependent and initially non-insulin requiring (LADA). This review discusses characteristics of autoimmune diabetes and specifically aims to illustrate the heterogeneity of the disease. PMID:27457237

  16. Bovine immunoglobulin protein isolates for the nutritional management of enteropathy

    PubMed Central

    Petschow, Bryon W; Blikslager, Anthony T; Weaver, Eric M; Campbell, Joy M; Polo, Javier; Shaw, Audrey L; Burnett, Bruce P; Klein, Gerald L; Rhoads, J Marc

    2014-01-01

    The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management of enteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy. PMID:25206275

  17. Bovine immunoglobulin protein isolates for the nutritional management of enteropathy.

    PubMed

    Petschow, Bryon W; Blikslager, Anthony T; Weaver, Eric M; Campbell, Joy M; Polo, Javier; Shaw, Audrey L; Burnett, Bruce P; Klein, Gerald L; Rhoads, J Marc

    2014-09-01

    The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management of enteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy. PMID:25206275

  18. Neonatal dexamethasone treatment increases susceptibility to experimental autoimmune disease in adult rats.

    PubMed

    Bakker, J M; Kavelaars, A; Kamphuis, P J; Cobelens, P M; van Vugt, H H; van Bel, F; Heijnen, C J

    2000-11-15

    Major concern has emerged about the possible long term adverse effects of glucocorticoid treatment, which is frequently used for the prevention of chronic lung disease in preterm infants. Here we show that neonatal glucocorticoid treatment of rats increases the severity (p< or = 0.01) and incidence (p< or =0.01) of the inflammatory autoimmune disease experimental autoimmune encephalomyelitis in adult life. In search of possible mechanisms responsible for the increased susceptibility to experimental autoimmune encephalomyelitis, we investigated the reactivity of the hypothalamo-pituitary-adrenal axis and of immune cells in adult rats after neonatal glucocorticoid treatment. We observed that neonatal glucocorticoid treatment reduces the corticosterone response after an LPS challenge in adult rats (p< or =0.001). Interestingly, LPS-stimulated macrophages of glucocorticoid-treated rats produce less TNF-alpha and IL-1beta in adult life than control rats (p<0.05). In addition, splenocytes obtained from adult rats express increased mRNA levels of the proinflammatory cytokines IFN-gamma (p<0.01) and TNF-beta (p<0.05) after neonatal glucocorticoid treatment. Apparently, neonatal glucocorticoid treatment has permanent programming effects on endocrine as well as immune functioning in adult life. In view of the frequent clinical application of glucocorticoids to preterm infants, our data demonstrate that neonatal glucocorticoid treatment may be a risk factor for the development of (auto)immune disease in man. PMID:11067955

  19. Olmesartan: sprue-like enteropathy.

    PubMed

    2016-05-01

    A cohort study conducted in 2014, using data from France's mandatory health insurance system, has shown a 10-fold increased risk of hospitalisation for enteropathy with olmesartan in comparison with other ARBs (sartans) or ACE inhibitors. The increased incidence of enteropathy with olmesartan compared with other ARBs or ACE inhibitors is well documented. The French drug regulatory agency, ANSM, informed healthcare professionals of these risks in 2014. Yet prescription rates for olmesartan remain high, and new cases of olmesartan-associated enteropathy continue to be reported. Patients would be better served if health professionals stopped using olmesartan and regulators withdrew this drug from the market. PMID:27280200

  20. Lawsonia intracellularis proliferative enteropathy in a foal.

    PubMed

    Feary, D J; Gebhart, C J; Pusterla, N

    2007-03-01

    A weanling foal was diagnosed with proliferative enteropathy caused by Lawsonia intracellularis based on history, clinical findings of depression, anorexia, weight loss, colic, diarrhea, and ventral edema, and a combination of serology and fecal PCR. An epidemiological investigation on the premises revealed that many of the other foals and adult horses were seropositive for L. intracellularis, despite being clinically normal, and identified a dog as a potential carrier and source of infection for the foal. The foal was successfully treated with a combination of azithromycin and rifampin. PMID:17410971

  1. Portal hypertensive enteropathy

    PubMed Central

    Mekaroonkamol, Parit; Cohen, Robert; Chawla, Saurabh

    2015-01-01

    Portal hypertensive enteropathy (PHE) is a condition that describes the pathologic changes and mucosal abnormalities observed in the small intestine of patients with portal hypertension. This entity is being increasingly recognized and better understood over the past decade due to increased accessibility of the small intestine made possible by the introduction of video capsule endoscopy and deep enteroscopy. Though challenged by its diverse endoscopic appearance, multiple scoring systems have been proposed to classify the endoscopic presentation and grade its severity. Endoscopic findings can be broadly categorized into vascular and non-vascular lesions with many subtypes of both categories. Clinical manifestations of PHE can range from asymptomatic incidental findings to fatal gastrointestinal hemorrhage. Classic endoscopic findings in the setting of portal hypertension may lead to a prompt diagnosis. Occasionally histopathology and cross sectional imaging like computed tomography or magnetic resonance imaging may be helpful in establishing a diagnosis. Management of overt bleeding requires multidisciplinary approach involving hepatologists, endoscopists, surgeons, and interventional radiologists. Adequate resuscitation, reduction of portal pressure, and endoscopic therapeutic intervention remain the main principles of the initial treatment. This article reviews the existing evidence on PHE with emphasis on its classification, diagnosis, clinical manifestations, endoscopic appearance, pathological findings, and clinical management. A new schematic management of ectopic variceal bleed is also proposed. PMID:25729469

  2. Combined treatment with sitagliptin and vitamin D in a patient with latent autoimmune diabetes in adults

    PubMed Central

    Rapti, E; Karras, S; Grammatiki, M; Mousiolis, A; Tsekmekidou, X; Potolidis, E; Zebekakis, P; Daniilidis, M

    2016-01-01

    Summary Latent autoimmune diabetes in adults (LADA) is a relatively new type of diabetes with a clinical phenotype of type 2 diabetes (T2D) and an immunological milieu characterized by high titers of islet autoantibodies, resembling the immunological profile of type 1 diabetes (T1D). Herein, we report a case of a young male, diagnosed with LADA based on both clinical presentation and positive anti-glutamic acid decarboxylase antibodies (GAD-abs), which were normalized after combined treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4) (sitagliptin) and cholecalciferol. Learning points Anti-glutamic acid decarboxylase antibodies (GAD-abs) titers in young patients being previously diagnosed as type 2 diabetes (T2D) may help establish the diagnosis of latent autoimmune diabetes in adults (LADA). Sitagliptin administration in patients with LADA might prolong the insulin-free period. Vitamin D administration in patients with LADA might have a protective effect on the progression of the disease. PMID:27252860

  3. Evidence for a Cystic Fibrosis Enteropathy

    PubMed Central

    Adriaanse, Marlou P. M.; van der Sande, Linda J. T. M.; van den Neucker, Anita M.; Menheere, Paul P. C. A.; Dompeling, Edward; Buurman, Wim A.; Vreugdenhil, Anita C. E.

    2015-01-01

    Background Previous studies have suggested the existence of enteropathy in cystic fibrosis (CF), which may contribute to intestinal function impairment, a poor nutritional status and decline in lung function. This study evaluated enterocyte damage and intestinal inflammation in CF and studied its associations with nutritional status, CF-related morbidities such as impaired lung function and diabetes, and medication use. Methods Sixty-eight CF patients and 107 controls were studied. Levels of serum intestinal-fatty acid binding protein (I-FABP), a specific marker for enterocyte damage, were retrospectively determined. The faecal intestinal inflammation marker calprotectin was prospectively studied. Nutritional status, lung function (FEV1), exocrine pancreatic insufficiency (EPI), CF-related diabetes (CFRD) and use of proton pump inhibitors (PPI) were obtained from the medical charts. Results Serum I-FABP levels were elevated in CF patients as compared with controls (p<0.001), and correlated negatively with FEV1 predicted value in children (r-.734, p<0.05). Faecal calprotectin level was elevated in 93% of CF patients, and correlated negatively with FEV1 predicted value in adults (r-.484, p<0.05). No correlation was found between calprotectin levels in faeces and sputum. Faecal calprotectin level was significantly associated with the presence of CFRD, EPI, and PPI use. Conclusion This study demonstrated enterocyte damage and intestinal inflammation in CF patients, and provides evidence for an inverse correlation between enteropathy and lung function. The presented associations of enteropathy with important CF-related morbidities further emphasize the clinical relevance. PMID:26484665

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

    PubMed Central

    Sategna, G; Solerio, E; Scaglione, N; Aimo, G; Mengozzi, G

    2001-01-01

    BACKGROUND AND AIMS—Duration of gluten exposure seems to predispose adolescents with coeliac disease to autoimmune diseases. In a retrospective cohort study, we assessed the relationship between autoimmune disorders and actual gluten exposure in patients in whom coeliac disease was diagnosed in adult life (⩾16 years).
METHODS—We screened for the presence of autoimmunity in 605 controls (16-84 years) and 422 patients (16-84 years), all of whom had been on gluten withdrawal for at least one year (median follow up 9.5 years). A logistic regression analysis, setting the prevalence of autoimmunity as the dependent variable, was employed to control for independent covariates as predictors of the risk of autoimmunity.
RESULTS—The prevalence of autoimmunity was threefold higher (p<0.00001) in patients than in controls. Mean duration of gluten exposure was 31.2 and 32.6 years for patients with or without autoimmunity. Logistic regression showed that increased age at diagnosis of coeliac disease was related to the prevalence of autoimmune disease while "actual gluten exposure" which takes into account diet compliance, follow up, and age at diagnosis of autoimmune disorders were not predictive for the risk of developing autoimmune diseases (odds ratio 0.82 per year).
CONCLUSION—The prevalence of autoimmune diseases in patients with a late coeliac disease diagnosis does not correlate with duration of gluten intake. Early exposure to gluten may modify the immunological response. Gluten withdrawal does not protect patients with a late diagnosis from autoimmune diseases.


Keywords: coeliac disease; autoimmune disorders; prevalence PMID:11559646

  5. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome associated with neonatal epidermolysis bullosa acquisita.

    PubMed

    Bis, Sabina; Maguiness, Sheilagh M; Gellis, Stephen E; Schneider, Lynda C; Lee, Pui Y; Notarangelo, Luigi D; Keles, Sevgi; Chatila, Talal A; Schmidt, Birgitta A; Miller, Daniel D

    2015-01-01

    We report the case of a 2-week-old boy who presented with a vesiculopustular, bullous eruption in the setting of autoimmune enteropathy, hypothyroidism, membranous nephropathy, Coombs-positive hemolytic anemia, and persistent eosinophilia. Immunologic testing revealed a deficiency of FOXP3-expressing regulatory T cells, and a diagnosis of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome was made. Histologic analysis, immunofluorescence, and enzyme-linked immunosorbent assay confirmed the bullous eruption as epidermolysis bullosa acquisita with associated collagen VII autoantibody production. The skin lesions responded to systemic immunosuppressant therapy and have regressed after allogeneic bone marrow transplantation. PMID:25790289

  6. Diabetic ketoacidosis as first presentation of latent autoimmune diabetes in adult.

    PubMed

    Nadhem, Omar; Nakhla, Essam; Smalligan, Roger D

    2015-01-01

    A 54-year-old white female with hypothyroidism presented with abdominal pain, nausea, vomiting, and diarrhea. She was found to have diabetic ketoacidosis (DKA) and admitted to our hospital for treatment. Laboratory workup revealed positive antiglutamic acid decarboxylase antibodies and subsequently she was diagnosed with latent onset autoimmune diabetes in adult (LADA). She was successfully treated with insulin with clinical and laboratory improvement. Diagnosis of LADA has been based on three criteria as given by The Immunology of Diabetes Society: (1) adult age of onset (>30 years of age); (2) presence of at least one circulating autoantibody (GADA/ICA/IAA/IA-2); and (3) initial insulin independence for the first six months. The importance of this case is the unlikely presentation of LADA. We believe that more research is needed to determine the exact proportion of LADA patients who first present with DKA, since similar cases have only been seen in case reports. Adult patients who are obese and have high blood sugar may deserve screening for LADA, especially in the presence of other autoimmune diseases. Those patients once diagnosed with LADA need extensive diabetic education including potentially serious events such as diabetic ketoacidosis. PMID:25834574

  7. Enteropathy associated T cell lymphoma: common in coeliac disease.

    PubMed

    Colleran, Gabrielle Christina; Cronin, Kevin Christopher; Casey, Mary; Bennani, Fadel; Tobbia, Iqdam; Barry, Kevin

    2009-01-01

    A 56-year-old male admitted with haematemesis and epigastric pain and severe weight loss on a background of coeliac disease. Computed tomography (CT) abdomen revealed a thickening of the mucosal folds of a short segment of jejunum. He deteriorated and had an exploratory laparotomy and bowel resection with side-side jejojejunal stapled anastomosis and extended right hemicolectomy and ileocolic anastomosis. Histology demonstrated multifocal high-grade malignant T cell lymphoma. Coeliac disease is a very common lifelong disorder. It is associated with osteoporosis, infertility, autoimmune disorders and increased risk of malignancy including an increased risk of non-Hodgkin's lymphoma (NHL) especially of the T cell type. Enteropathy-type T cell lymphoma is associated with a very poor prognosis. There is significant evidence that adherence to a gluten-free diet decreases the risk of developing enteropathy-type T cell lymphoma and helps to prevent development of autoimmune diseases, diabetes mellitus and osteoporosis in patients with coeliac disease. PMID:21686880

  8. Maternal deprivation of rat pups increases clinical symptoms of experimental autoimmune encephalomyelitis at adult age.

    PubMed

    Teunis, Marc A T; Heijnen, Cobi J; Sluyter, Frans; Bakker, Joost M; Van Dam, Anne-Marie M W; Hof, Maleen; Cools, Alexander R; Kavelaars, Annemieke

    2002-12-01

    Maternal deprivation of neonatal animals has been shown to induce long-lasting changes in the reactivity of the neuroendocrine system. The aim of the present study was to investigate whether maternal deprivation also affects susceptibility to immune-mediated diseases such as experimental autoimmune encephalomyelitis (EAE) in adult life. To this end, 9-day-old rat pups were subjected to a short-lasting maternal deprivation for a period of 24 h. At the age of 8 weeks, we induced EAE in these rats by immunization with myelin basic protein (MBP) in complete Freund's adjuvant. Our data demonstrate that short-lasting maternal deprivation induces a marked increase in the severity of EAE in the animals in later life. The histopathological evaluation of spinal cord and cerebellum corresponded with the observed differences in clinical symptoms of EAE. Moreover, neonatal maternal deprivation affects macrophage functioning at adult age. In contrast, no differences were observed in in vitro mitogen- and MBP-induced cytokine production by splenocytes. LPS-induced corticosterone release did not differ either between maternally deprived and control animals. We conclude that short-lasting neonatal maternal deprivation of rat pups has long-lasting consequences for macrophage activity and for susceptibility to the inflammatory autoimmune disease EAE. PMID:12446005

  9. Few Foxp3⁺ regulatory T cells are sufficient to protect adult mice from lethal autoimmunity.

    PubMed

    Mayer, Christian T; Ghorbani, Peyman; Kühl, Anja A; Stüve, Philipp; Hegemann, Maike; Berod, Luciana; Gershwin, M Eric; Sparwasser, Tim

    2014-10-01

    Foxp3 specifies the Treg cell lineage and is indispensable for immune tolerance. Accordingly, rare Foxp3 mutations cause lethal autoimmunity. The mechanisms precipitating more prevalent human autoimmune diseases are poorly understood, but involve a combination of genetic and environmental factors. Many autoimmune diseases associate with a partial Treg-cell dysfunction, yet mouse models reflecting such complex pathophysiological processes are rare. Around 95% of Foxp3(+) Treg cells can be specifically depleted in bacterial artifical chromosome (BAC)-transgenic Depletion of REGulatory T cells (DEREG) mice through diphtheria toxin (DT) treatment. However, Treg-cell depletion fails to cause autoimmunity in adult DEREG mice for unclear reasons. By crossing Foxp3(GFP) knock-in mice to DEREG mice, we introduced additional genetic susceptibility that does not affect untreated mice. Strikingly, DT treatment of DEREG × Foxp3(GFP) mice rapidly causes autoimmunity characterized by blepharitis, tissue damage, and autoantibody production. This inflammatory disease is associated with augmented T-cell activation, increased Th2 cytokine production and myeloproliferation, and is caused by defective Treg-cell homeostasis, preventing few DT-insensitive Treg cells from repopulating the niche after Treg-cell depletion. Our study provides important insights into self-tolerance. We further highlight DEREG × Foxp3(GFP) mice as a model to investigate the role of environmental factors in precipitating autoimmunity. This may help to better understand and treat human autoimmunity. PMID:25042334

  10. Severe Enteropathy From Mycophenolate Mofetil

    PubMed Central

    Shaikh, Bilal; Hunt, Jettie; Spiegel, Adam

    2016-01-01

    The adverse effects of mycophenolate mofetil on the colon are well known. However, isolated small intestinal involvement resulting in diarrhea and severe weight loss is infrequently reported in the literature. We present the case of a 45-year-old woman on mycophenolate mofetil following renal transplant, who presented with abdominal pain and weight loss. An esophagogastroduodenoscopy and colonoscopy with biopsies were normal. A small bowel capsule study revealed extensive enteropathy of jejunum and ileum that was confirmed on a push enteroscopy with biopsies. Her symptoms completely resolved after being switched to enteric-coated mycophenolic acid. PMID:26958559

  11. Changing aspects of radiation enteropathy

    SciTech Connect

    Morgenstern, L.; Hart, M.; Lugo, D.; Friedman, N.B.

    1985-11-01

    Fifty-two patients with radiation enteropathy secondary to radiation for abdominal or pelvic malignant neoplasms are described. This series (1977 to 1984) is compared with a series of 50 patients from the same institution over an earlier period (1961 to 1977). Intestinal obstruction was the principal complication in both series; 96% of the patients underwent either intestinal resection or anastomotic bypass of the affected segment. Changes that have occurred since the last report are as follows: changes in source of radiation energy (linear accelerator); less evidence of mucosal damage; increased serosal reaction (''serosal peel''); and increased use of elemental diets, parenteral nutrition, and long intestinal tubes in surgical management. Since postoperative radiation injury occurs most frequently in the pelvis, new developments for the exclusion of small bowel from the pelvis during radiation are reviewed. Changes in fractionation of radiation dosage should also be considered in patients with enteric symptoms during radiation therapy.

  12. Intestinal epithelial dysplasia (tufting enteropathy).

    PubMed

    Goulet, Olivier; Salomon, Julie; Ruemmele, Frank; de Serres, Natacha Patey-Mariaud; Brousse, Nicole

    2007-01-01

    Intestinal epithelial dysplasia (IED), also known as tufting enteropathy, is a congenital enteropathy presenting with early-onset severe intractable diarrhea causing sometimes irreversible intestinal failure. To date, no epidemiological data are available, however, the prevalence can be estimated at around 1/50,000-100,000 live births in Western Europe. The prevalence seems higher in areas with high degree of consanguinity and in patients of Arabic origin. Infants develop within the first days after birth a watery diarrhea persistent in spite of bowel rest and parenteral nutrition. Some infants are reported to have associated choanal rectal or esophageal atresia. IED is thought to be related to abnormal enterocytes development and/or differentiation. Nonspecific punctuated keratitis was reported in more than 60% of patients. Histology shows various degree of villous atrophy, with low or without mononuclear cell infiltration of the lamina propria but specific histological abnormalities involving the epithelium with disorganization of surface enterocytes with focal crowding, resembling tufts. Several associated specific features were reported, including abnormal deposition of laminin and heparan sulfate proteoglycan (HSPG) in the basement membrane, increased expression of desmoglein and ultrastructural changes in the desmosomes, and abnormal distribution of alpha2beta1 integrin adhesion molecules. One model of transgenic mice in which the gene encoding the transcription factor Elf3 is disrupted have morphologic features resembling IED. Parental consanguinity and/or affected siblings suggest an autosomal recessive transmission but the causative gene(s) have not been yet identified making prenatal diagnosis unavailable. Some infants have a milder phenotype than others but in most patients, the severity of the intestinal malabsorption even with enteral feeding make them totally dependent on daily long-term parenteral nutrition with a subsequent risk of complications

  13. Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes.

    PubMed

    Sepúlveda, Maria; Armangue, Thaís; Martinez-Hernandez, Eugenia; Arrambide, Georgina; Sola-Valls, Nuria; Sabater, Lidia; Téllez, Nieves; Midaglia, Luciana; Ariño, Helena; Peschl, Patrick; Reindl, Markus; Rovira, Alex; Montalban, Xavier; Blanco, Yolanda; Dalmau, Josep; Graus, Francesc; Saiz, Albert

    2016-07-01

    The aim of this study was to report the clinical spectrum associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) in adult patients, and to assess whether phenotypic variants are dependent on recognition of rodent MOG epitopes. We retrospectively analyzed the features, course and outcome of 56 patients whose samples were investigated by brain tissue immunohistochemistry and cell-based assays using human and rodent MOG. The median age at symptom onset was 37 years (range 18-70); 35 patients (63 %) were female. After a median follow-up of 43 months (range 4-554), only 14 patients (25 %) developed a neuromyelitis optica spectrum disorder (NMOSD), 27 patients (47 %) retained the initial diagnosis of isolated optic neuritis, 7 (12 %) of longitudinally extensive transverse myelitis, and 2 (4 %) of acute disseminated encephalomyelitis; 6 patients (11 %) developed atypical demyelinating syndromes (4 had relapsing episodes of short myelitis lesions which in one occurred with optic neuritis; 1 had relapsing brainstem symptoms, and 1 relapsing demyelinating encephalomyelitis). The course was frequently associated with relapses (71 %) and good outcome. Twenty-seven patients (49 %) had antibodies that recognized rodent MOG epitopes, and 9 of them (16 %) showed a myelin staining pattern in rodent tissue. Only the myelin staining pattern was linked to NMOSD (p = 0.005). In conclusion, MOG autoimmunity in adult patients associates with a clinical spectrum wider than the one expected for patients with suspected NMOSD and overall good outcome. Antibodies to rodent MOG epitopes do not associate with any phenotypic variant. PMID:27147513

  14. Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals.

    PubMed

    Miller, A; Lider, O; Abramsky, O; Weiner, H L

    1994-05-01

    Antigen-driven tolerance is an effective method for suppression of autoimmune diseases. Adult animals can be tolerized against the induction of experimental autoimmune encephalomyelitis (EAE) by both oral and parenteral administration of myelin basic protein (MBP). We have found that in contrast to previous studies of neonatal tolerance in which parenterally administered autoantigens induced tolerance, the oral administration of MBP in neonatal rats did not result in tolerization to MBP, but instead, primed for immunologic responses. Proliferative responses to MBP and its encephalitogenic epitope were present in animals fed with MBP as neonates and co-culture of encephalitogenic T cells with cells from neonatal rats fed with MBP were associated with enhanced MBP responses rather than the suppression observed with cells from adult rats fed with MBP. Furthermore, neonates fed with MBP and immunized 6-8 weeks later with MBP in adjuvant to induce EAE revealed enhancement of disease severity, and were not protected from a second attack upon active reinduction of EAE. Subcutaneous injection of soluble MBP into neonates had no effect on EAE induction as adults, whereas intraperitoneal injection of MBP in neonates was associated with marked suppression of disease in adults. Suppression of EAE began to appear in animals fed with MBP at 4 weeks of age, and was similar to oral tolerance in adult animals when animals were fed at 6 weeks of age. These results suggest that immaturity of the immunoregulatory network associated with oral tolerance and sensitization to autoantigens via the gut in the neonatal period may contribute to the pathogenesis of autoimmune diseases. PMID:7514126

  15. An association analysis of the HLA gene region in latent autoimmune diabetes in adults

    PubMed Central

    2011-01-01

    Aims/hypothesis Pathophysiological similarities between latent autoimmune diabetes in adults (LADA) and type 1 diabetes indicate an overlap in genetic susceptibility. HLA-DRB1 and HLA-DQB1 are major susceptibility genes for type 1 diabetes but studies of these genes in LADA have been limited. Our aim was to define patterns of HLA-encoded susceptibility/protection in a large, well characterised LADA cohort, and to establish association with disease and age at diagnosis. Materials and methods Patients with LADA (n=387, including 211 patients from the UK Prospective Diabetes Study) and non-diabetic control subjects (n=327) were of British/Irish European origin. The HLA-DRB1 and -DQB1 genes were genotyped by sequence-specific PCR. Results As in type 1 diabetes mellitus, DRB1*0301_DQB1*0201 (odds ratio [OR]=3.08, 95% CI 2.32–4.12, p=1.2× 10−16) and DRB1*0401_DQB1*0302 (OR=2.57, 95% CI 1.80–3.73, p=4.5×10−8) were the main susceptibility haplotypes in LADA, and DRB1*1501_DQB1*0602 was protective (OR=0.21, 95% CI 0.13–0.34, p=4.2×10−13). Differential susceptibility was conferred by DR4 subtypes: DRB1*0401 was predisposing (OR=1.79, 95% CI 1.35–2.38, p=2.7×10−5) whereas DRB1*0403 was protective (OR=0.37, 95% CI 0.13–0.97, p=0.033). The highest-risk genotypes were DRB1*0301/DRB1*0401 and DQB1*0201/DQB1*0302 (OR=5.14, 95% CI 2.68–10.69, p=1.3×10−8; and OR=6.88, 95% CI 3.54–14.68, p=1.2×10−11, respectively). These genotypes and those containing DRB1*0401 and DQB1*0302 associated with a younger age at diagnosis in LADA, whereas genotypes containing DRB1*1501 and DQB1*0602 associated with an older age at diagnosis. Conclusions/interpretation Patterns of susceptibility at the HLA-DRB1 and HLA-DQB1 loci in LADA are similar to those reported for type 1 diabetes, supporting the hypothesis that autoimmune diabetes occurring in adults is an age-related extension of the pathophysiological process presenting as childhood-onset type 1 diabetes. PMID

  16. Involvement of heat shock proteins in gluten-sensitive enteropathy

    PubMed Central

    Sziksz, Erna; Pap, Domonkos; Veres, Gábor; Fekete, Andrea; Tulassay, Tivadar; Vannay, Ádám

    2014-01-01

    Gluten-sensitive enteropathy, also known as coeliac disease (CD), is an autoimmune disorder occurring in genetically susceptible individuals that damages the small intestine and interferes with the absorption of other nutrients. As it is triggered by dietary gluten and related prolamins present in wheat, rye and barley, the accepted treatment for CD is a strict gluten-free diet. However, a complete exclusion of gluten-containing cereals from the diet is often difficult, and new therapeutic strategies are urgently needed. A class of proteins that have already emerged as drug targets for other autoimmune diseases are the heat shock proteins (HSPs), which are highly conserved stress-induced chaperones that protect cells against harmful extracellular factors. HSPs are expressed in several tissues, including the gastrointestinal tract, and their levels are significantly increased under stress circumstances. HSPs exert immunomodulatory effects, and also play a crucial role in the maintenance of epithelial cell structure and function, as they are responsible for adequate protein folding, influence the degradation of proteins and cell repair processes after damage, and modulate cell signalling, cell proliferation and apoptosis. The present review discusses the involvement of HSPs in the pathophysiology of CD. Furthermore, HSPs may represent a useful therapeutic target for the treatment of CD due to the cytoprotective, immunomodulatory, and anti-apoptotic effects in the intestinal mucosal barrier. PMID:24914370

  17. Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia.

    PubMed

    Ureshino, Hiroshi; Shindo, Takero; Nishikawa, Hiroyoshi; Watanabe, Nobukazu; Watanabe, Eri; Satoh, Natsuko; Kitaura, Kazutaka; Kitamura, Hiroaki; Doi, Kazuko; Nagase, Kotaro; Kimura, Hiromi; Samukawa, Makoto; Kusunoki, Susumu; Miyahara, Masaharu; Shin-I, Tadasu; Suzuki, Ryuji; Sakaguchi, Shimon; Kimura, Shinya

    2016-08-01

    The regulatory T cells (Treg) with the most potent immunosuppressive activity are the effector Tregs (eTreg) with a CD45RA(-)Foxp3(++)CCR4(+) phenotype. Adult T-cell leukemia (ATL) cells often share the Treg phenotype and also express CCR4. Although mogamulizumab, a monoclonal antibody to CCR4, shows marked antitumor effects against ATL and peripheral T-cell lymphoma, concerns have been raised that it may induce severe autoimmune immunopathology by depleting eTregs. Here, we present case reports for two patients with ATL who responded to mogamulizumab but developed a severe skin rash and autoimmune brainstem encephalitis. Deep sequencing of the T-cell receptor revealed that ATL cells and naturally occurring Tregs within the cell population with a Treg phenotype can be clearly distinguished according to CADM1 expression. The onset of skin rash and brainstem encephalitis was coincident with eTreg depletion from the peripheral blood, whereas ATL relapses were coincident with eTreg recovery. These results imply that eTreg numbers in the peripheral blood sensitively reflect the equilibrium between antitumor immunity and autoimmunity, and that mogamulizumab might suppress ATL until the eTreg population recovers. Close monitoring of eTreg numbers is crucial if we are to provide immunomodulatory treatments that target malignancy without severe adverse events. Cancer Immunol Res; 4(8); 644-9. ©2016 AACR. PMID:27215229

  18. NSAID enteropathy and bacteria: a complicated relationship.

    PubMed

    Syer, Stephanie D; Blackler, Rory W; Martin, Rebeca; de Palma, Giada; Rossi, Laura; Verdu, Elena; Bercik, Premek; Surette, Michael G; Aucouturier, Anne; Langella, Philippe; Wallace, John L

    2015-04-01

    The clinical significance of small intestinal damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs) remains under-appreciated. It occurs with greater frequency than the damage caused by these drugs in the upper gastrointestinal tract, but is much more difficult to diagnose and treat. Although the pathogenesis of NSAID enteropathy remains incompletely understood, it is clear that bacteria, bile, and the enterohepatic circulation of NSAIDs are all important factors. However, they are also interrelated with one another. Bacterial enzymes can affect the cytotoxicity of bile and are essential for enterohepatic circulation of NSAIDs. Gram-negative bacteria appear to be particularly important in the pathogenesis of NSAID enteropathy, possibly through release of endotoxin. Inhibitors of gastric acid secretion significantly aggravate NSAID enteropathy, and this effect is due to significant changes in the intestinal microbiome. Treatment with antibiotics can, in some circumstances, reduce the severity of NSAID enteropathy, but published results are inconsistent. Specific antibiotic-induced changes in the microbiota have not been causally linked to prevention of intestinal damage. Treatment with probiotics, particularly Bifidobacterium, Lactobacillus, and Faecalibacteriaum prausnitzii, has shown promising effects in animal models. Our studies suggest that these beneficial effects are due to colonization by the bacteria, rather than to products released by the bacteria. PMID:25572030

  19. Enteropathies in the Developing World: Neglected Effects on Global Health

    PubMed Central

    Prendergast, Andrew; Kelly, Paul

    2012-01-01

    A spectrum of enteropathies, characterized by small intestinal inflammation, reduced absorptive capacity, and increased intestinal permeability, commonly affect people in developing countries. This subclinical intestinal pathology facilitates microbial translocation across the compromised intestinal barrier, leading to chronic systemic inflammation that may adversely impact health. Environmental enteropathy (EE), ubiquitous among people living in unhygienic conditions, likely mediates two interlinked public health problems of childhood, stunting and anemia, and underlies poor oral vaccine efficacy in developing countries. Human immunodeficiency virus (HIV) enteropathy, which frequently overlaps with EE, may contribute to immune activation and modulate HIV disease progression. The interacting effects of infection and enteropathy drive a vicious cycle that can propagate severe acute malnutrition, which underlies almost half of under-5-y deaths. Enteropathies are therefore highly prevalent, interacting causes of morbidity and mortality in developing countries. Interventions to prevent or ameliorate enteropathies have potential to improve the health of millions of people in developing countries. PMID:22556071

  20. Adult coeliac disease.

    PubMed

    Marmouz, F

    2007-01-01

    Coeliac disease is an auto-immune inflammatory reaction characterized by a partial or total villi's atrophy of the proximal small intestine occuring after ingestion of gluten in genetically predisposed patients. The classic form is much more frequent in children. Thereby there has been a misevaluation and improper treatment of coeliac disease in adults who suffer more from asymptomatica and atypical forms. Currently the only effective treatment is a strict gluten free diet for life. However recent researches brought a new light on the matter. Now oats as a causative factor is controvertial. The introduction of some moderate intestinal lesions (pre-atrophic with intra-epithelial hyperlymphocytosis qualified as "weak enteropathies") in the definition of coeliac disease might be possible. Moreover the way to diagnose has evolved as serological tests and markers are more used due to their efficiency. PMID:17375738

  1. Autoimmune cytopenias after umbilical cord blood transplantation in adults with hematological malignancies: a single-center experience.

    PubMed

    Sanz, J; Arango, M; Carpio, N; Montesinos, P; Moscardó, F; Martín, G; López, F; Jarque, I; Lorenzo, I; de la Rubia, J; Solves, P; Boluda, B; Salazar, C; Cañigral, C; Sanz, M A; Sanz, G F

    2014-08-01

    We describe incidence, clinical features, serological data, response to therapy and outcome of autoimmune cytopenias (ACs), including autoimmune hemolytic anemia (AIHA) and autoimmune thrombocytopenia (AIT) in a series of 281 consecutive adults with hematological malignancies that received single-unit umbilical cord blood transplantation (UCBT) at a single institution. AIHA was diagnosed in 15 patients at a median time of 181 days (range, 25-543), 12 of them had cold antibodies (IgM). The 3-year cumulative incidence (CI) of AIHA was 5.4% (CI 95% 2.7-8.1). Concomitant infections at the time of AIHA were present in 10 patients. Five out of nine patients that received corticosteroids achieved either a PR or a CR, whereas six out of eight patients that received rituximab responded. Four patients developed AIT giving a 3-year CI of 1.4% (CI 95% 0-2.8), concomitant infections were present in three of them. Multivariable analysis showed that development of chronic GVHD (relative risk (RR) 4; 95% CI 1.1-13.7; P=0.03) and diagnosis of CML (RR 4.3; 95% CI 1.5-12.7; P=0.008) were associated with an increased risk of AC. In conclusion, AIHA and AIT are relevant and clinically significant complications in UCBT recipients, especially among those that develop chronic GVHD. Response to therapy is sub-optimal, and rituximab should be considered as a therapeutic option, in this setting were most patients had cold AIHA and a serological profile similar to that seen in cold agglutinin disease. PMID:24887383

  2. The biopsy pathology of non-coeliac enteropathy.

    PubMed

    Greenson, Joel K

    2015-01-01

    Tropical sprue (TS) is a malabsorption syndrome of presumed infectious aetiology that affects residents of (or visitors to) the tropics. The histological changes of TS are similar to those of coeliac disease, with increased intraepithelial lymphocytes being central to both. Unlike in coeliac disease, however, a completely flat small bowel biopsy is uncommon in TS. TS typically involves the terminal ileum, whereas coeliac disease does not. Small intestinal bacterial overgrowth (SIBO) has been defined as an increase in number and/or a change in the type of bacteria in the upper gut. Conditions that predispose to SIBO are largely those that decrease or interfere with small bowel motility. The mucosal histology is variable, and may include modest villous blunting accompanied by increased lamina propria and epithelial inflammation. Autoimmune enteropathy (AE) is a family of rare diseases that share common themes such as immunodeficiency states and autoantibodies. AE cases typically have marked villous atrophy similar to that in fully developed coeliac disease, but they lack the intense surface epithelial lymphocytosis. Apoptosis and lymphocyte infiltration at the base of the crypts, crypt abscesses and cryptitis are also seen. Patients with anti-goblet cell antibodies can have a lack of goblet cells, endocrine cells, and Paneth cells. PMID:25234408

  3. Declined plasma sfrp5 concentration in patients with type 2 diabetes and latent autoimmune diabetes in adults

    PubMed Central

    Cheng, Liqing; Zhang, Dongmei; Chen, Bing

    2015-01-01

    Objective: Secreted frizzled-related protein 5 (sfrp5), like adiponectin, has been identified as a novel insulin-sensitising and anti-inflammatory adipokine. Our objective was to determine whether differences of circulating plasma sfrp5 concentration exist among type 2 diabetes (T2D), latent autoimmune diabetes in adults (LADA) and healthy population. Methods: Enzyme-linked immuno sorbent assay was employed to detect the circulating sfrp5 level in plasma, and other lab tests such as fasting glucose and creatinine were also examined. Correlation analysis between sfrp5 and characteristics of subjects was conducted IBM SPSS Statistics and GraphPad Prism. Results: Circulating sfrp5 level was significantly decreased in T2D and LADA patients plasma compared with that in healthy control (14.14±11.91ng/mL, 14.82±11.27ng/mL, 22.98±12.36ng/mL, respectively), although no differences was observed between LADA and T2D groups. Furthermore, we found sfrp5 was correlated with homeostasis model assessment of insulin resistance (HOMA-IR), diabetes duration and BMI. Finally we found sfrp5 was still negatively correlated with HOMA-IR after being adjusted for disease duration and BMI(r= -0.315, P< 0.05). Conclusions: Our results support a role for SFRP5 as a protective factor in the pathogenesis of autoimmune diabetes and facilitate a novel aspect for diabetes research. PMID:26150852

  4. [Autoimmune hemolytic anemia in children].

    PubMed

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

    2015-01-01

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

  5. Lawsonia intracellularis and equine proliferative enteropathy.

    PubMed

    Page, Allen E; Slovis, Nathan M; Horohov, David W

    2014-12-01

    Lawsonia intracellularis is the etiologic agent for equine proliferative enteropathy (EPE), which typically affects weanling and yearling horses. In North America, EPE cases often occur between August and January, although cases outside of this time frame have been reported. Clinical signs of EPE are usually nonspecific and include lethargy, pyrexia, anorexia, peripheral edema, weight loss, colic, and diarrhea. Diagnosis is based on the presence of hypoproteinemia and hypoalbuminemia along with clinical signs and positive commercial serologic and/or molecular testing. Treatment requires the use of antimicrobials with good intracellular penetration and supportive care to prevent or decrease secondary complications. PMID:25300636

  6. Autoimmune Hepatitis

    MedlinePlus

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

  7. Bifidobacterium longum CECT 7347 Modulates Immune Responses in a Gliadin-Induced Enteropathy Animal Model

    PubMed Central

    Laparra, José Moisés; Olivares, Marta; Gallina, Onofrio; Sanz, Yolanda

    2012-01-01

    Coeliac disease (CD) is an autoimmune disorder triggered by gluten proteins (gliadin) that involves innate and adaptive immunity. In this study, we hypothesise that the administration of Bifidobacterium longum CECT 7347, previously selected for reducing gliadin immunotoxic effects in vitro, could exert protective effects in an animal model of gliadin-induced enteropathy. The effects of this bacterium were evaluated in newborn rats fed gliadin alone or sensitised with interferon (IFN)-γ and fed gliadin. Jejunal tissue sections were collected for histological, NFκB mRNA expression and cytokine production analyses. Leukocyte populations and T-cell subsets were analysed in peripheral blood samples. The possible translocation of the bacterium to different organs was determined by plate counting and the composition of the colonic microbiota was quantified by real-time PCR. Feeding gliadin alone reduced enterocyte height and peripheral CD4+ cells, but increased CD4+/Foxp3+ T and CD8+ cells, while the simultaneous administration of B. longum CECT 7347 exerted opposite effects. Animals sensitised with IFN-γ and fed gliadin showed high cellular infiltration, reduced villi width and enterocyte height. Sensitised animals also exhibited increased NFκB mRNA expression and TNF-α production in tissue sections. B. longum CECT 7347 administration increased NFκB expression and IL-10, but reduced TNF-α, production in the enteropathy model. In sensitised gliadin-fed animals, CD4+, CD4+/Foxp3+ and CD8+ T cells increased, whereas the administration of B. longum CECT 7347 reduced CD4+ and CD4+/Foxp3+ cell populations and increased CD8+ T cell populations. The bifidobacterial strain administered represented between 75–95% of the total bifidobacteria isolated from all treated groups, and translocation to organs was not detected. These findings indicate that B. longum attenuates the production of inflammatory cytokines and the CD4+ T-cell mediated immune response in an animal model

  8. Clustering of immunological, metabolic and genetic features in latent autoimmune diabetes in adults: evidence from principal component analysis.

    PubMed

    Pes, Giovanni Mario; Delitala, Alessandro Palmerio; Errigo, Alessandra; Delitala, Giuseppe; Dore, Maria Pina

    2016-06-01

    Latent autoimmune diabetes in adults (LADA) which accounts for more than 10 % of all cases of diabetes is characterized by onset after age 30, absence of ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. The principal component (PC) analysis is a statistical approach used for finding patterns in data of high dimension. In this study the PC analysis was applied to a set of variables from a cohort of Sardinian LADA patients to identify a smaller number of latent patterns. A list of 11 variables including clinical (gender, BMI, lipid profile, systolic and diastolic blood pressure and insulin-free time period), immunological (anti-GAD65, anti-IA-2 and anti-TPO antibody titers) and genetic features (predisposing gene variants previously identified as risk factors for autoimmune diabetes) retrieved from clinical records of 238 LADA patients referred to the Internal Medicine Unit of University of Sassari, Italy, were analyzed by PC analysis. The predictive value of each PC on the further development of insulin dependence was evaluated using Kaplan-Meier curves. Overall 4 clusters were identified by PC analysis. In component PC-1, the dominant variables were: BMI, triglycerides, systolic and diastolic blood pressure and duration of insulin-free time period; in PC-2: genetic variables such as Class II HLA, CTLA-4 as well as anti-GAD65, anti-IA-2 and anti-TPO antibody titers, and the insulin-free time period predominated; in PC-3: gender and triglycerides; and in PC-4: total cholesterol. These components explained 18, 15, 12, and 12 %, respectively, of the total variance in the LADA cohort. The predictive power of insulin dependence of the four components was different. PC-2 (characterized mostly by high antibody titers and presence of predisposing genetic markers

  9. [Polyglandular autoimmune syndromes : An overview].

    PubMed

    Komminoth, P

    2016-05-01

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

  10. Association of major histocompatibility complex class 1 chain-related gene a dimorphism with type 1 diabetes and latent autoimmune diabetes in adults in the Algerian population.

    PubMed

    Raache, Rachida; Belanteur, Khadidja; Amroun, Habiba; Benyahia, Amel; Heniche, Amel; Azzouz, Malha; Mimouni, Safia; Gervais, Thibaud; Latinne, Dominique; Boudiba, Aissa; Attal, Nabila; Abbadi, Mohamed Cherif

    2012-04-01

    Major histocompatibility complex class I chain-related gene A (MICA-129) dimorphism was investigated in 73 autoimmune diabetes patients (type 1 diabetes and latent autoimmune diabetes in adults) and 75 controls from Algeria. Only MICA-129 Val allele and MICA-129 Val/Val genotype frequencies were higher among patients than in the control group. Statistical analysis of the estimated extended HLA-DR-DQ-MICA haplotypes shown that individual effects of MICA alleles on HLA-DQ2-DR3-MICA-129 Val/Val and HLA-DQ8-DR4-MICA-129 Val/Val haplotypes were significantly higher in patients than in the control groups. These preliminary data might suggest a relevant role of MICA-129 Val/Val single nucleotide polymorphism (weak/weak binders of NKG2D receptor) in the pathogenesis of T1D and LADA. PMID:22323559

  11. Association of Major Histocompatibility Complex Class 1 Chain-Related Gene A Dimorphism with Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Algerian Population

    PubMed Central

    Belanteur, Khadidja; Amroun, Habiba; Benyahia, Amel; Heniche, Amel; Azzouz, Malha; Mimouni, Safia; Gervais, Thibaud; Latinne, Dominique; Boudiba, Aissa; Attal, Nabila; Abbadi, Mohamed Cherif

    2012-01-01

    Major histocompatibility complex class I chain-related gene A (MICA-129) dimorphism was investigated in 73 autoimmune diabetes patients (type 1 diabetes and latent autoimmune diabetes in adults) and 75 controls from Algeria. Only MICA-129 Val allele and MICA-129 Val/Val genotype frequencies were higher among patients than in the control group. Statistical analysis of the estimated extended HLA-DR-DQ-MICA haplotypes shown that individual effects of MICA alleles on HLA-DQ2-DR3-MICA-129 Val/Val and HLA-DQ8-DR4-MICA-129 Val/Val haplotypes were significantly higher in patients than in the control groups. These preliminary data might suggest a relevant role of MICA-129 Val/Val single nucleotide polymorphism (weak/weak binders of NKG2D receptor) in the pathogenesis of T1D and LADA. PMID:22323559

  12. Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study.

    PubMed

    Ting, Wei-Hsin; Chien, Ming-Nan; Lo, Fu-Sung; Wang, Chao-Hung; Huang, Chi-Yu; Lin, Chiung-Ling; Lin, Wen-Shan; Chang, Tzu-Yang; Yang, Horng-Woei; Chen, Wei-Fang; Lien, Ya-Ping; Cheng, Bi-Wen; Lin, Chao-Hsu; Chen, Chia-Ching; Wu, Yi-Lei; Hung, Chen-Mei; Li, Hsin-Jung; Chan, Chon-In; Lee, Yann-Jinn

    2016-01-01

    Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21-1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15-1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27-2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22-2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D' = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population. PMID:27111218

  13. Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study

    PubMed Central

    Lo, Fu-Sung; Wang, Chao-Hung; Huang, Chi-Yu; Lin, Chiung-Ling; Lin, Wen-Shan; Chang, Tzu-Yang; Yang, Horng-Woei; Chen, Wei-Fang; Lien, Ya-Ping; Cheng, Bi-Wen; Lin, Chao-Hsu; Chen, Chia-Ching; Wu, Yi-Lei; Hung, Chen-Mei; Li, Hsin-Jung; Chan, Chon-In; Lee, Yann-Jinn

    2016-01-01

    Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21–1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15–1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27–2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22–2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D’ = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population. PMID:27111218

  14. Capsule Endoscopy for Portal Hypertensive Enteropathy

    PubMed Central

    2016-01-01

    Portal hypertensive enteropathy (PHE) is a mucosal abnormality of the small bowel that is observed in patients with portal hypertension (PH) and can lead to gastrointestinal bleeding and anemia. The pathogenesis is still not completely understood. The introduction of new endoscopic methods, including capsule endoscopy (CE) or balloon-assisted enteroscopy, has increased the detection of these abnormalities. CE can also serve as a road map for deciding subsequent interventions and evaluating the treatment effect. The prevalence of PHE is reportedly 40–70% in patients with PH. Endoscopic findings can be roughly divided into vascular and nonvascular lesions such as inflammatory-like lesions. Traditionally, PHE-associated factors include large esophageal varices, portal hypertensive gastropathy or colopathy, Child-Turcotte-Pugh class B or C, a history of variceal treatment, and acute gastrointestinal bleeding. More recently, on using scoring systems, a high computed tomography or transient elastography score was reportedly PHE-related factors. However, the prevalence of PHE and its related associated factors remain controversial. The management of PHE has not yet been standardized. It should be individualized according to each patient's situation, the availability of therapy, and each institutional expertise. PMID:26819613

  15. Capsule Endoscopy for Portal Hypertensive Enteropathy.

    PubMed

    Jeon, Seong Ran; Kim, Jin-Oh

    2016-01-01

    Portal hypertensive enteropathy (PHE) is a mucosal abnormality of the small bowel that is observed in patients with portal hypertension (PH) and can lead to gastrointestinal bleeding and anemia. The pathogenesis is still not completely understood. The introduction of new endoscopic methods, including capsule endoscopy (CE) or balloon-assisted enteroscopy, has increased the detection of these abnormalities. CE can also serve as a road map for deciding subsequent interventions and evaluating the treatment effect. The prevalence of PHE is reportedly 40-70% in patients with PH. Endoscopic findings can be roughly divided into vascular and nonvascular lesions such as inflammatory-like lesions. Traditionally, PHE-associated factors include large esophageal varices, portal hypertensive gastropathy or colopathy, Child-Turcotte-Pugh class B or C, a history of variceal treatment, and acute gastrointestinal bleeding. More recently, on using scoring systems, a high computed tomography or transient elastography score was reportedly PHE-related factors. However, the prevalence of PHE and its related associated factors remain controversial. The management of PHE has not yet been standardized. It should be individualized according to each patient's situation, the availability of therapy, and each institutional expertise. PMID:26819613

  16. When uncommon and common coalesce: adult onset Still's disease associated with breast augmentation as part of autoimmune syndrome induced by adjuvants (ASIA).

    PubMed

    Dagan, A; Kogan, M; Shoenfeld, Y; Segal, G

    2016-06-01

    Adult onset Still's disease (AOSD) is an uncommon, multisystemic, auto-inflammatory disorder, while breast augmentation is a very common cosmetic procedure. We describe a case in which these two coalesce, AOSD, manifested with pleuritis and pericarditis, developed after breast mammoplasty. The pathogenetic, missing link, behind the development of AOSD following mammoplasty, is thought to be the autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA). We reviewed other cases of AOSD associated with breast mammoplasty published to date and the literature regarding AOSD and ASIA syndrome. The review is followed by a short debate of whether silicone implants should be explanted in similar, future cases. PMID:25604318

  17. Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy

    PubMed Central

    Kelly, Paul; Besa, Ellen; Zyambo, Kanekwa; Louis-Auguste, John; Lees, James; Banda, Themba; Soko, Rose; Banda, Rosemary; Amadi, Beatrice; Watson, Alastair

    2016-01-01

    Introduction Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE. PMID:27050312

  18. Autoimmunity in visual loss.

    PubMed

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

    2016-01-01

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

  19. Autoimmune hepatitis

    MedlinePlus

    ... diseases. These include: Graves disease Inflammatory bowel disease Rheumatoid arthritis Scleroderma Sjogren syndrome Systemic lupus erythematosus Thyroiditis Type 1 diabetes Ulcerative colitis Autoimmune hepatitis may occur in family ...

  20. Celiac disease and autoimmune thyroid disease.

    PubMed

    Ch'ng, Chin Lye; Jones, M Keston; Kingham, Jeremy G C

    2007-10-01

    Celiac disease (CD) or gluten sensitive enteropathy is relatively common in western populations with prevalence around 1%. With the recent availability of sensitive and specific serological testing, many patients who are either asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD have modest increases in risks of malignancy and mortality compared to controls. The mortality among CD patients who comply poorly with a gluten-free diet is greater than in compliant patients. The pattern of presentation of CD has altered over the past three decades. Many cases are now detected in adulthood during investigation of problems as diverse as anemia, osteoporosis, autoimmune disorders, unexplained neurological syndromes, infertility and chronic hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased prevalence of CD has been found in patients with autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease. Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary biliary cirrhosis in prospective studies. Conversely, there is also an increased prevalence of immune based disorders among patients with CD. The pathogenesis of co-existent autoimmune thyroid disease and CD is not known, but these conditions share similar HLA haplotypes and are associated with the gene encoding cytotoxic T-lymphocyte-associated antigen-4. Screening high risk patients for CD, such as those with autoimmune diseases, is a reasonable strategy given the increased prevalence. Treatment of CD with a gluten-free diet should reduce the recognized complications of this disease and provide benefits in both general health and perhaps life expectancy. It also improves glycemic control in patients with type 1 diabetes mellitus and enhances the absorption of medications for associated hypothyroidism and osteoporosis. It

  1. Autoimmune myelopathies.

    PubMed

    Flanagan, Eoin P

    2016-01-01

    Autoimmune myelopathies are a heterogeneous group of immune-mediated spinal cord disorders with a broad differential diagnosis. They encompass myelopathies with an immune attack on the spinal cord (e.g., aquaporin-4-IgG (AQP4-IgG) seropositive neuromyelitis optica (NMO) and its spectrum disorders (NMOSD)), myelopathies occurring with systemic autoimmune disorders (which may also be due to coexisting NMO/NMOSD), paraneoplastic autoimmune myelopathies, postinfectious autoimmune myelopathies (e.g., acute disseminated encephalomyelitis), and myelopathies thought to be immune-related (e.g., multiple sclerosis and spinal cord sarcoidosis). Spine magnetic resonance imaging is extremely useful in the evaluation of autoimmune myelopathies as the location of signal change, length of the lesion, gadolinium enhancement pattern, and evolution over time narrow the differential diagnosis considerably. The recent discovery of multiple novel neural-specific autoantibodies accompanying autoimmune myelopathies has improved their classification. These autoantibodies may be pathogenic (e.g., AQP4-IgG) or nonpathogenic and more reflective of a cytotoxic T-cell-mediated autoimmune response (collapsin response mediator protein-5(CRMP5)-IgG). The presence of an autoantibody may help guide cancer search, assist treatment decisions, and predict outcome/relapse. With paraneoplastic myelopathies the initial goal is detection and treatment of the underlying cancer. The aim of immunotherapy in all autoimmune myelopathies is to maximize reversibility, maintain benefits (while preventing relapse), and minimize side effects. PMID:27112686

  2. Autoimmune movement disorders.

    PubMed

    Mckeon, Andrew; Vincent, Angela

    2016-01-01

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

  3. Autoimmune hepatitis

    MedlinePlus

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

  4. Autoimmune disorders

    MedlinePlus

    ... exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or viruses) or drugs may trigger changes that confuse the immune system. This may happen ...

  5. [Autoimmune encephalitis].

    PubMed

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

    2015-01-01

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

  6. Increased severity of experimental autoimmune encephalomyelitis in rats tolerized as adults but not neonatally to a protective TCR V beta 8 CDR2 idiotope.

    PubMed

    Offner, H; Malotky, M K; Pope, L; Vainiene, M; Celnik, B; Miller, S D; Vandenbark, A A

    1995-01-15

    The ability of synthetic V region peptides to induce regulatory T cells and Abs in rodents and humans provides clear evidence that these idiotopes do not naturally induce tolerance. In this study, we investigated the ability of TCR V beta 8.2 peptides to experimentally induce specific T cell tolerance, as measured by loss of Ag-specific proliferation and delayed-type hypersensitivity responses, and by increased susceptibility to experimental autoimmune encephalomyelitis (EAE). We found that both neonatal and adult exposure to V beta 8.2-39-59 or V beta 8-44-54 peptides could induce efficient T cell tolerance, resulting in a significant inhibition of peptide-specific proliferative responses. In addition, neonatal tolerance resulted in a partial reduction in delayed-type hypersensitivity response and an inability to vaccinate against EAE after adult immunization with the tolerizing peptide. We further evaluated the contribution of naturally induced TCR-specific responses to EAE resistance induced by challenging neonatally or adult tolerized rats with myelin basic protein in adjuvant. The clinical course of EAE was not significantly altered in rats tolerized neonatally to V beta 8.2 peptides, but both the severity and incidence of mortality from EAE was increased in rats tolerized as adults with V beta 8.2 peptides conjugated to syngeneic splenocytes. These results demonstrate that V beta 8.2 peptides are tolerogenic as well as immunogenic. Moreover, the observation of different effects of neonatal vs adult tolerization on the course of EAE suggests either the emergence of additional protective idiotopes after neonatal tolerization and/or mechanistic differences in the two tolerance-inducing protocols. Most importantly, the enhancement of clinical EAE in rats tolerized as adults with V beta 8.2 peptides provides evidence for an innate regulatory role of the CDR2 idiotope in recovery from EAE. PMID:7529291

  7. Enterococcus hirae enteropathy with ascending cholangitis and pancreatitis in a kitten.

    PubMed

    Lapointe, J M; Higgins, R; Barrette, N; Milette, S

    2000-05-01

    A 2-month-old female Persian cat that had been showing episodes of anorexia and diarrhea for the previous 4 weeks was presented in shock and died 2 days later. Numerous Gram-positive cocci were located along the brush border of small intestinal villi, without significant inflammatory infiltration. Similar bacteria were present within hepatic bile ducts and pancreatic ducts and were associated with suppurative inflammation and exfoliation of epithelial cells. Culture of the liver and lung yielded bacteria identified as Enterococcus hirae. Fecal culture from an asymptomatic adult female from the same cattery also yielded large numbers of E. hirae. To our knowledge, this is the first report of E. hirae enteropathy in a cat and the first report of ascending cholangitis and ductal pancreatitis caused by an Enterococcus spp. PMID:10810996

  8. Autoimmune encephalopathies

    PubMed Central

    Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep

    2014-01-01

    Over the last 10 years the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of twelve autoimmune encephatilic disorders, grouped by syndromes and approached from a clinical perspective. Anti-NMDAR encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases. PMID:25315420

  9. The autoimmune diseases

    SciTech Connect

    Rose, N.R.; Mackay, I.R.

    1985-01-01

    This book contains 25 chapters. Some of the chapter titles are: Genetic Predisposition to Autoimmune Diseases; Systemic Lupus Erythematosus; Autoimmune Aspects of Rheumatoid Arthritis; Immunology of Insulin-Dependent Diabetes; and Adrenal Autoimmunity and Autoimmune Polyglandular Syndromes.

  10. Autoimmune synaptopathies.

    PubMed

    Crisp, Sarah J; Kullmann, Dimitri M; Vincent, Angela

    2016-02-01

    Autoantibodies targeting proteins at the neuromuscular junction are known to cause several distinct myasthenic syndromes. Recently, autoantibodies targeting neurotransmitter receptors and associated proteins have also emerged as a cause of severe, but potentially treatable, diseases of the CNS. Here, we review the clinical evidence as well as in vitro and in vivo experimental evidence that autoantibodies account for myasthenic syndromes and autoimmune disorders of the CNS by disrupting the functional or structural integrity of synapses. Studying neurological and psychiatric diseases of autoimmune origin may provide new insights into the cellular and circuit mechanisms underlying a broad range of CNS disorders. PMID:26806629

  11. HLA antigen expression in enteropathy associated T cell lymphoma.

    PubMed Central

    Ashton-Key, M; Singh, N; Pan, L X; Smith, M E

    1996-01-01

    AIMS: To investigate the occurrence of abnormal patterns of HLA-ABC and HLA-DR expression in enteropathy associated T cell lymphoma and to relate such abnormalities to the Epstein Barr virus (EBV) status of the tumours. METHODS: Eleven enteropathy associated T cell lymphomas were immunostained with HC10 (HLA-ABC heavy chain) and TAL 1B5 (HLA-DR alpha chain) monoclonal antibodies and polyclonal anti-beta 2 microglobulin (beta 2m, the HLA-ABC light chain) antibodies. In situ hybridisation for EBV using EBER probes was performed on all cases. RESULTS: Tumour cells of two of 11 patients were EBER positive. One of these showed partial, and the other, complete loss of beta 2m. HLA-DR expression was undetectable in both patients. Of the remaining nine EBER negative tumours, two were HLA-ABC heavy chain negative or showed only occasional positive cells and five of nine showed partial or complete loss of the HLA-ABC light chain, beta 2m. Seven of the nine cases were either negative for HLA-DR or showed weak expression in a proportion of tumour cells. CONCLUSIONS: These data show that low or absent HLA-ABC and HLA-DR antigen expression occurs commonly in enteropathy associated T cell lymphoma. These abnormal patterns of HLA expression may be associated with escape from immune attack which, in a minority of patients, could be directed against EBV antigens. Images PMID:8813950

  12. Interactions between intestinal pathogens, enteropathy and malnutrition in developing countries

    PubMed Central

    Prendergast, Andrew J.; Kelly, Paul

    2016-01-01

    Purpose of review This review focuses on recent data highlighting the interactions between intestinal pathogens, enteropathy and malnutrition in developing countries, which drive morbidity and mortality and hinder the long-term developmental potential of children. Recent findings Diarrhoea remains the second commonest cause of death in children below 5 years, and malnutrition underlies 45% of all child deaths. Even in the absence of diarrhoea, subclinical pathogen carriage and enteropathy are almost universal in developing countries. Here, we review recent studies addressing the causes and consequences of diarrhoea; emerging data on environmental influences that govern postnatal development of the gut and microbiota; current concepts of environmental enteric dysfunction; and recent intervention trials in the field. We highlight the interactions between these processes, whereby intestinal pathogens drive a cycle of gut damage, malabsorption, chronic inflammation and failed mucosal regeneration, leading to malnutrition and susceptibility to further enteric infections. Summary Efforts to improve child survival and long-term developmental potential need to address the overlapping and interacting effects of diarrhoea, enteropathy and malnutrition. Recent insights from human and animal studies suggest potential targets for intervention. PMID:26967147

  13. Immunological changes following protein losing enteropathy after surgery total cavopulmonary connection (TCPC) by cytomics

    NASA Astrophysics Data System (ADS)

    Bocsi, József; Lenz, Dominik; Mittag, Anja; Sauer, Ursula; Wild, Lena; Hess, John; Schranz, Dietmar; Hambsch, Jörg; Schneider, Peter; Tárnok, Attila

    2008-02-01

    Complex immunophenotyping single-cell analysis are essential for systems biology and cytomics. The application of cytomics in immunology and cardiac research and diagnostics is very broad, ranging from the better understanding of the cardiovascular cell biology to the identification of heart function and immune consequences after surgery. TCPC or Fontan-type circulation is an accepted palliative surgery for patients with a functionally univentricular heart. Protein-losing enteropathy (PLE), the enteric loss of proteins, is a potential late complication after TCPC surgery. PLE etiology is poorly understood, but immunological factors seem to play a role. This study was aimed to gain insight into immune phenotype alterations following post-TCPC PLE. Patients were studied during routine follow-up up to 5yrs after surgery, blood samples of TCPC patients without (n=21, age 6.8+/-2.6 years at surgery; mean+/-SD) and with manifest PLE (n=12, age 12.8+/- 4.5 years at sampling) and age matched healthy children (control, n=22, age 8.6+/-2.5 years) were collected. Routine laboratory, immune phenotype and serological parameters were determined. Following PLE the immune phenotype dramatically changed with signs of acute inflammation (increased neutrophil and monocyte count, CRP, IL-8). In contrast, lymphocyte count (NK-cells, αβTCR +CD4 +, αβTCR +CD8 + cells) decreased (p<0.001). The residual T-cells had elevated CD25 and CD69 expression. In PLE-patients unique cell populations with CD3 +αβ/γδTCR - and αβTCR +CD4 -8 - phenotype were present in increased frequencies. Our studies show dramatically altered leukocyte phenotype after PLE in TCPC patients. These alterations resemble to changes in autoimmune diseases. We conclude that autoimmune processes may play a role in etiology and pathophysiology of PLE.

  14. Autoimmunity and Turner's syndrome.

    PubMed

    Lleo, Ana; Moroni, Luca; Caliari, Lisa; Invernizzi, Pietro

    2012-05-01

    Turner Syndrome (TS) is a common genetic disorder, affecting female individuals, resulting from the partial or complete absence of one sex chromosome, and occurring in approximately 50 per 100,000 liveborn girls. TS is associated with reduced adult height and with gonadal dysgenesis, leading to insufficient circulating levels of female sex steroids and to infertility. Morbidity and mortality are increased in TS but average intellectual performance is within the normal range. TS is closely associated to the presence of autoantibodies and autoimmune diseases (AID), especially autoimmune thyroiditis and inflammatory bowel disease. Despite the fact that the strong association between TS and AID is well known and has been widely studied, the underlying immunopathogenic mechanism remains partially unexplained. Recent studies have displayed how TS patients do not show an excess of immunogenic risk markers. This is evocative for a higher responsibility of X-chromosome abnormalities in the development of AID, and particularly of X-genes involved in immune response. For instance, the long arm of the X chromosome hosts a MHC-locus, so the loss of that region may lead to a deficiency in immune regulation. Currently no firm guidelines for diagnosis exist. In conclusion, TS is a condition associated with a number of autoimmune manifestations. Individuals with TS need life-long medical attention. As a consequence of these findings, early diagnosis and regular screening for potential associated autoimmune conditions are essential in the medical follow-up of TS patients. PMID:22154619

  15. Thyroid autoimmunity and polyglandular endocrine syndromes.

    PubMed

    Wémeau, Jean-Louis; Proust-Lemoine, Emmanuelle; Ryndak, Amélie; Vanhove, Laura

    2013-01-01

    Even though autoimmune thyroiditis is considered as the most emblematic type of organ-specific autoimmune disorder of autoimmunity, autoimmune thyroid diseases can be associated with other autoimmune endocrine failures or non-endocrine diseases (namely vitiligo, pernicious anemia, myasthenia gravis, autoimmune gastritis, celiac disease, hepatitis). Thyroid disorders, which are the most frequent expression of adult polyendocrine syndrome type 2, occur concomitantly with or secondarily to insulinodependent diabetes, premature ovarian failure, Addison's disease (Schmidt syndrome, or Carpenter syndrome if associated with diabetes). Testicular failure and hypoparathyroidism are unusual. The disease is polygenic and multifactorial. Disorders of thyroid autoimmunity are, surprisingly, very rare in polyendocrine syndrome type 1 (or APECED) beginning during childhood. They are related to mutations of the AIRE gene that encodes for a transcriptional factor implicated in central and peripheral immune tolerance. Hypothyroidism can also be observed in the very rare IPEX and POEMS syndromes. PMID:23624130

  16. [Autoimmune encephalitis].

    PubMed

    Günther, Albrecht; Schubert, Julia; Brämer, Dirk; Witte, Otto Wilhelm

    2016-08-01

    Autoimmune encephalitis, an inflammatory disease of the brain, is usually attributed to antibody-mediated damage and dysfunction of neuronal structures. A distinction is made between onconeuronal antibodies (directed against intracellular neuronal antigens with resulting paraneoplastic neurological syndromes) and antibodies directed against neuronal cell surface proteins (with resulting synaptic encephalopathies). Anti-NMDA-Receptor-Encephalitis, the most common form of autoimmune encephalopathy, is characterized by a phased course of disease. Early disease phase involves nonspecific prodromes (fatigue, fever, headache) which lead to family doctor or emergency department consultation. Subsequently, neuropsychiatric behavioural problems, seizures, disturbance of memory and finally coma, dysautonomia and respiratory insufficiency often result in major complications (e.g. status epilepticus) necessitating intensive care treatment. The diagnosis is secured by detection of auto-antibodies in serum or cerebrospinal fluid. An intensive search for tumors is also recommended. The treatment of autoimmune encephalitis comprises of immunomodulatory and immunosuppessive strategies. Tumor therapy is the most important treatment of autoimmune encephalitis by onconeuronal antibodies. PMID:27557073

  17. Autoimmune Hepatitis

    MedlinePlus

    ... provider will closely monitor and manage any side effects that may occur, as high doses of prednisone are often prescribed to treat autoimmune hepatitis. Immune system suppressors. Medications that suppress the immune system prevent the body from making autoantibodies and block the immune reaction ...

  18. Effect of Lactobacillus GG on intestinal integrity in Malawian children at risk of tropical enteropathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tropical enteropathy is an asymptomatic villous atrophy of the small bowel that is prevalent in the developing world and is associated with altered intestinal function and integrity. The histology of tropical enteropathy resembles that seen in small-bowel bacterial overgrowth. This study tested the...

  19. Low-dose autologous in vitro opsonized erythrocytes. Radioimmune method and autologous opsonized erythrocytes for refractory autoimmune thrombocytopenic purpura in adults

    SciTech Connect

    Ambriz, R.; Munoz, R.; Pizzuto, J.; Quintanar, E.; Morales, M.; Aviles, A.

    1987-01-01

    Adult patients with chronic autoimmune thrombocytopenic purpura (ATP), which proved refractory to various treatments, received a single dose of autologous in vitro opsonized erythrocytes with 100 micrograms of anti-D IgG. In 1983, 30 of these patients were treated with autologous erythrocytes that had been opsonized and labeled with 25 mCi (740 MBq) of technetium Tc 99m; this treatment was designated as the radioimmune method. Favorable responses were noted in 36% of patients so treated. In 1985, another group of 16 patients with refractory ATP received therapy with autologous opsonized erythrocytes (AOPE) and 55% of these patients showed favorable responses. Five (17%) of the patients treated using the radioimmune method attained a complete, long-term (greater than 35 months) remission of their ATP, and five (31%) of the patients treated using AOPE remained in complete remission over 270 days after cessation of therapy. Major complications were not seen. We concluded that the interaction of macrophages with low-dose AOPE is a successful therapeutic approach in ATP refractory to standard treatment.

  20. Autoimmune liver disease panel

    MedlinePlus

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

  1. Everolimus for Primary Intestinal Lymphangiectasia With Protein-Losing Enteropathy.

    PubMed

    Ozeki, Michio; Hori, Tomohiro; Kanda, Kaori; Kawamoto, Norio; Ibuka, Takashi; Miyazaki, Tatsuhiko; Fukao, Toshiyuki

    2016-03-01

    Primary intestinal lymphangiectasia (PIL), also known as Waldmann's disease, is an exudative enteropathy resulting from morphologic abnormalities in the intestinal lymphatics. In this article, we describe a 12-year-old boy with PIL that led to protein-losing enteropathy characterized by diarrhea, hypoalbuminemia associated with edema (serum albumin level: 1.0 g/dL), and hypogammaglobulinemia (serum IgG level: 144 mg/dL). Severe hypoalbuminemia, electrolyte abnormalities, and tetany persisted despite a low-fat diet and propranolol. Everolimus (1.6 mg/m(2)/day) was added to his treatment as an antiangiogenic agent. With everolimus treatment, the patient's diarrhea resolved and replacement therapy for hypoproteinemia was less frequent. Hematologic and scintigraphy findings also improved (serum albumin level: 2.5 g/dL). There were no adverse reactions during the 12-month follow-up. To the best of our knowledge, this is the first report of everolimus use in a patient with PIL. PMID:26908672

  2. Autoimmune pancreatitis.

    PubMed

    Omiyale, Ayodeji Oluwarotimi

    2016-06-01

    Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids. PMID:27294040

  3. Autoimmune pancreatitis

    PubMed Central

    2016-01-01

    Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids. PMID:27294040

  4. Autoimmune Encephalitis

    PubMed Central

    Leypoldt, Frank; Wandinger, Klaus-Peter; Bien, Christian G; Dalmau, Josep

    2016-01-01

    The term autoimmune encephalitis is used to describe a group of disorders characterised by symptoms of limbic and extra-limbic dysfunction occurring in association with antibodies against synaptic antigens and proteins localised on the neuronal cell surface. In recent years there has been a rapidly expanding knowledge of these syndromes resulting in a shift in clinical paradigms and new insights into pathogenic mechanisms. Since many patients respond well to immunosuppressive treatment, the recognition of these disorders is of utmost importance. In general, there are no brain-imaging modalities or biomarkers specific of these disorders other than the demonstration of the neuronal antibodies. A disease classification based on these antibodies provides information on prognosis and paraneoplastic aetiology. This article focuses on recent clinical advances, newly characterised antibodies and treatment approaches to these disorders. PMID:27330568

  5. The Clinical Significance of Glycoprotein Phospholipase D Levels in Distinguishing Early Stage Latent Autoimmune Diabetes in Adults and Type 2 Diabetes

    PubMed Central

    Qin, Wen; Liang, Yu-Zhen; Qin, Bao-Yu; Zhang, Jia-Li; Xia, Ning

    2016-01-01

    Autoantibodies have been widely used as markers of latent autoimmune diabetes in adults (LADA); however, the specificity and sensitivity of autoantibodies as markers of LADA are weak compared with those found in type 1 diabetes (T1DM). In this study, we aimed to identify other plasma proteins as potential candidates that can be used effectively to determine early stage LADA and type 2 diabetes (T2DM) to facilitate early diagnosis and treatment. These issues were addressed by studying new-onset ‘classic’ T1DM (n = 156), LADA (n = 174), T2DM (n = 195) and healthy cohorts (n = 166). Plasma samples were obtained from the four cohorts. We employed isobaric tag for relative and absolute quantitation (iTRAQ) together with liquid chromatography tandem mass spectrometry (LC-MS) to identify plasma proteins with significant changes in LADA. The changes were validated by Western blot and ELISA analyses. Among the four cohorts, 311 unique proteins were identified in three iTRAQ runs, with 157 present across the three data sets. Among them, 49/311 (16.0%) proteins had significant changes in LADA compared with normal controls, including glycoprotein phospholipase D (GPLD1), which was upregulated in LADA. Western blot and ELISA analyses showed that GPLD1 levels were higher in both LADA and T1DM cohorts than in both T2DM and healthy cohorts, while there were no significant differences in the plasma concentrations of GPLD1 between the LADA and T1DM cohorts. GPLD1 is implicated as a potential candidate plasma protein for determining early stage LADA and T2DM. PMID:27351175

  6. Lawsonia intracellularis infection and proliferative enteropathy in foals.

    PubMed

    Pusterla, Nicola; Gebhart, Connie

    2013-11-29

    Equine proliferative enteropathy (EPE) is a disease of foals caused by the obligate intracellular organism Lawsonia intracellularis. This organism is unique in that it causes proliferation of infected enterocytes, resulting in thickening of the intestinal epithelium, most often the small intestine. This disease affects mainly weanling foals and causes fever, lethargy, peripheral edema, diarrhea, colic and weight loss. The diagnosis of EPE may be challenging and relies on the presence of hypoproteinemia, thickening of segments of the small intestinal wall observed on abdominal ultrasonography, positive serology and molecular detection of L. intracellularis in feces. The epidemiology and genetic basis for pathogenesis for this disease is beginning to be elucidated. Phenotypic traits, genomic features, and gene expression profiles during L. intracellularis infection in vitro and in vivo are presented. In addition, this article reviews the epidemiology, pathological and clinicopathological findings, diagnosis, and control of EPE. PMID:23871678

  7. Equine proliferative enteropathy--a review of recent developments.

    PubMed

    Pusterla, N; Gebhart, C J

    2013-07-01

    Equine proliferative enteropathy (EPE) is a disease of foals caused by the obligate intracellular organism Lawsonia intracellularis. This emerging disease affects mainly weanling foals and causes fever, lethargy, peripheral oedema, diarrhoea, colic and weight loss. The diagnosis of EPE may be challenging and relies on the presence of hypoproteinaemia, thickening of segments of the small intestinal wall observed upon abdominal ultrasonography, positive serology and molecular detection of L. intracellularis in faeces. Although the clinical entity, diagnostic approach and treatment of EPE are well established and described, the epidemiology for this disease has remained largely unaddressed. This article focuses on new developments in the field of EPE, including epidemiology, pathophysiology, clinical signs, diagnosis, treatment and prevention. PMID:23662705

  8. Food Protein-Induced Enterocolitis Syndrome, Allergic Proctocolitis, and Enteropathy.

    PubMed

    Feuille, Elizabeth; Nowak-Węgrzyn, Anna

    2015-08-01

    Food protein-induced enterocolitis (FPIES), allergic proctocolitis (FPIAP), and enteropathy (FPE) are among a number of immune-mediated reactions to food that are thought to occur primarily via non-IgE-mediated pathways. All three are typically present in infancy and are triggered most commonly by cow's milk protein. The usual presenting features are vomiting with lethargy and dehydration in FPIES; bloody and mucous stools in FPIAP; and diarrhea with malabsorption and failure to thrive in FPE. Diagnosis is based on convincing history and resolution of symptoms with food avoidance; confirmatory diagnostic testing other than food challenge is lacking. The mainstay of management is avoidance of the suspected inciting food, with interval challenge to assess for resolution, which usually occurs in the first years of life. Studies published in the past few years clarify common presenting features, report additional culprit foods, address potential biomarkers, and suggest new management strategies. PMID:26174434

  9. Dietary requirement for serum-derived bovine immunoglobulins in the clinical management of patients with enteropathy.

    PubMed

    Petschow, Bryon W; Burnett, Bruce P; Shaw, Audrey L; Weaver, Eric M; Klein, Gerald L

    2015-01-01

    A variety of human disease conditions are associated with chronic intestinal disorders or enteropathies that are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Such disruptions in the homeostasis of the gastrointestinal (GI) tract can lead to symptoms of abdominal pain and discomfort, bloating, abnormal bowel function, and malabsorption of nutrients. While significant advances have been made in understanding the factors that influence the complex and fragile balance between the gut microbiota, intestinal epithelial cell integrity, and the underlying immune system, effective therapies for restoring intestinal balance during enteropathy are still not available. Numerous studies have demonstrated the ability of oral immunoglobulins to improve weight gain, support gut barrier function, and reduce the severity of enteropathy in animals. More recently, studies in humans provide evidence that serum-derived bovine immunoglobulin/protein isolate is safe and improves nutritional status and GI symptoms in patients with enteropathy associated with irritable bowel syndrome or infection with the human immunodeficiency virus. This review summarizes studies showing the impact of enteropathy on nutritional status and how specially formulated bovine immunoglobulins may help restore intestinal homeostasis and nutritional status in patients with specific enteropathies. Such protein preparations may provide distinct nutritional support required for the dietary management of patients who, because of therapeutic or chronic medical needs, have limited or impaired capacity to digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or other special medically determined nutrient requirements that cannot be satisfied by changes to the normal diet alone. PMID:25142170

  10. The potential of mesenchymal stem cells in the management of radiation enteropathy

    PubMed Central

    Chang, P-Y; Qu, Y-Q; Wang, J; Dong, L-H

    2015-01-01

    Although radiotherapy is effective in managing abdominal and pelvic malignant tumors, radiation enteropathy is still unavoidable. This disease severely affects the quality of life of cancer patients due to some refractory lesions, such as intestinal ischemia, mucositis, ulcer, necrosis or even perforation. Current drugs or prevailing therapies are committed to alleviating the symptoms induced by above lesions. But the efficacies achieved by these interventions are still not satisfactory, because the milieus for tissue regeneration are not distinctly improved. In recent years, regenerative therapy for radiation enteropathy by using mesenchymal stem cells is of public interests. Relevant results of preclinical and clinical studies suggest that this regenerative therapy will become an attractive tool in managing radiation enteropathy, because mesenchymal stem cells exhibit their pro-regenerative potentials for healing the injuries in both epithelium and endothelium, minimizing inflammation and protecting irradiated intestine against fibrogenesis through activating intrinsic repair actions. In spite of these encouraging results, whether mesenchymal stem cells promote tumor growth is still an issue of debate. On this basis, we will discuss the advances in anticancer therapy by using mesenchymal stem cells in this review after analyzing the pathogenesis of radiation enteropathy, introducing the advances in managing radiation enteropathy using regenerative therapy and exploring the putative actions by which mesenchymal stem cells repair intestinal injuries. At last, insights gained from the potential risks of mesenchymal stem cell-based therapy for radiation enteropathy patients may provide clinicians with an improved awareness in carrying out their studies. PMID:26247725

  11. Proliferative Hemorrhagic Enteropathy in Swine: An Outbreak and Review of the Literature

    PubMed Central

    Yates, W. D. G.; Clark, E. G.; Osborne, A. D.; Enweani, C. C.; Radostits, O. M.; Theede, A.

    1979-01-01

    An account is given of an acute outbreak of hemorrhagic enteric disease in 34 young adult boars of primarily Yorkshire breeding at a performance testing station in Western Canada. Two of the boars died. A diagnosis of proliferative hemorrhagic enteropathy was made on the basis of clinical signs, gross necropsy and histopathological lesions. Campylobacter-like bacteria were seen in the apical cytoplasm of epithelial cells of the ileal mucosa by Warthin-Faulkner stain on histological sections, but were not isolated on culture. Treatment with several drugs simultaneously was associated with termination of the outbreak, but the therapeutic effect was not controlled by leaving some animals untreated. Reported sequelae, such as porcine intestinal adenomatosis, were not present at necropsy or slaughter of pigs surviving the outbreak, but all were killed no longer than two months after the first case was observed. This outbreak is discussed in the context of previously reported hemorrhagic enteric conditions of pigs. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:396978

  12. Update on Autoimmune Hepatitis

    PubMed Central

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

    2015-01-01

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

  13. CEOP/IVE/GDP Compared With CEOP as the First-line Therapy for Newly Diagnosed Adult Patients With PTCL

    ClinicalTrials.gov

    2016-04-18

    Peripheral T-Cell Lymphoma; Angioimmunoblastic T Cell Lymphoma; ALK-negative Anaplastic Large Cell Lymphoma; Enteropathy Associated T Cell Lymphoma; Subcutaneous Panniculitis Like T Cell Lymphoma; Acute Adult T-Cell Leukemia/Lymphoma

  14. Autoimmune Inner Ear Disease

    MedlinePlus

    ... Find an ENT Doctor Near You Autoimmune Inner Ear Disease Autoimmune Inner Ear Disease Patient Health Information ... with a hearing loss. How Does the Healthy Ear Work? The ear has three main parts: the ...

  15. Two Japanese cases of dermatitis herpetiformis associated each with lung cancer and autoimmune pancreatitis but showing no intestinal symptom or circulating immunoglobulin A antibodies to any known antigens.

    PubMed

    Shigeta, Mika; Saiki, Minoru; Tsuruta, Daisuke; Ohata, Chika; Ishii, Norito; Ono, Fumitake; Hamada, Takahiro; Dainichi, Teruki; Furumura, Minao; Zone, John J; Karpati, Sarolta; Sitaru, Cassian; Hashimoto, Takashi

    2012-12-01

    Dermatitis herpetiformis (DH) is common in some Caucasian populations but extremely rare in Japanese, probably because of different immunogenetic backgrounds. We report two Japanese DH cases with typical clinical, histological and direct immunofluorescence features. However, no symptom of gluten-sensitive enteropathy was shown. The diagnosis was confirmed by eliminating other autoimmune blistering diseases by indirect immunofluorescence, enzyme-linked immunosorbent assays and immunoblotting. However, circulating immunoglobulin (Ig)A anti-endomysium, reticulin and gliadin antibodies were not detected. IgA antibodies to tissue and epidermal transglutaminases were also negative. One case was associated with lung cancer and the other one with autoimmune pancreatitis. On review of 17 cases of DH reported in Japan over the previous 10 years, including our cases, one case was associated with gluten-sensitive enteropathy, four with malignant neoplasms, two with autoimmune systemic disorders and one with psoriasis. Although our cases were typical of DH in clinical, histopathological and IgA deposit features, they showed different human leukocyte antigen haplotypes, no gluten-sensitive enteropathy and no DH-specific IgA antibodies, including those to epidermal and tissue transglutaminases. These results suggest that studies of unique characteristics in Japanese DH patients should facilitate further understanding of pathogenesis in DH. PMID:22963165

  16. Perspectives on autoimmunity

    SciTech Connect

    Cohen, I.R.

    1987-01-01

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

  17. Interactions between zinc deficiency and environmental enteropathy in developing countries.

    PubMed

    Lindenmayer, Greta W; Stoltzfus, Rebecca J; Prendergast, Andrew J

    2014-01-01

    Zinc deficiency affects one-fifth of the world's population and leads to substantial morbidity and mortality. Environmental enteropathy (EE), a subclinical pathology of altered intestinal morphology and function, is almost universal among people living in developing countries and affects long-term growth and health. This review explores the overlapping nature of these 2 conditions and presents evidence for their interaction. EE leads to impaired zinc homeostasis, predominantly due to reduced absorptive capacity arising from disturbed intestinal architecture, and zinc deficiency exacerbates several of the proposed pathways that underlie EE, including intestinal permeability, enteric infection, and chronic inflammation. Ongoing zinc deficiency likely perpetuates the adverse outcomes of EE by worsening malabsorption, reducing intestinal mucosal immune responses, and exacerbating systemic inflammation. Although the etiology of EE is predominantly environmental, zinc deficiency may also have a role in its pathogenesis. Given the impact of both EE and zinc deficiency on morbidity and mortality in developing countries, better understanding the relation between these 2 conditions may be critical for developing combined interventions to improve child health. PMID:24425714

  18. Environmental Enteropathy: Elusive but Significant Subclinical Abnormalities in Developing Countries.

    PubMed

    Watanabe, Koji; Petri, William A

    2016-08-01

    Environmental enteropathy/Environmental enteric dysfunction (EE/EED) is a chronic disease of small intestine characterized by gut inflammation and barrier disruption, malabsorption and systemic inflammation in the absence of diarrhea. It is predominantly diseases of children in low income countries and is hypothesized to be caused by continuous exposure to fecally contaminated food, water and fomites. It had not been recognized as a priority health issue because it does not cause overt symptoms and was seen in apparently healthy individuals. However, there is a growing concern of EE/EED because of its impact on longitudinal public health issues, such as growth faltering, oral vaccine low efficacy and poor neurocognitive development. Recent works have provided important clues to unravel its complex pathogenesis, and suggest possible strategies for controlling EE/EED. However, effective diagnostic methods and interventions remain unsettled. Here, we review the existing literature, especially about its pathogenesis, and discuss a solution for children living in the developing world. PMID:27495791

  19. A randomized, double-blind, placebo-controlled trial of Rifaximin, a nonabsorbable antibiotic, in the treatment of tropical enteropathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tropical enteropathy is characterized by an increased urinary lactulose-to-mannitol (L:M) ratio on a site-specific sugar absorption test and is associated with increased intestinal permeability and decreased nutrient absorptive capacity. The etiology of tropical enteropathy is postulated to be intes...

  20. CVID enteropathy- a rare cause of chronic diarrhea in a child.

    PubMed

    Patel, Jignesh; Kumar, Arvind; Agasti, Anantakumar; Choksey, Ajay; Phadke, Aniruddha; Sawant, Prabha

    2012-10-01

    Common variable immunodeficiency (CVID) is a rare primary immunodeficiency disease characterized by hypogammaglobulinemia and recurrent bacterial infections especially in respiratory and gastrointestinal systems. The authors present here a case of CVID with uncommon gastrointestinal manifestation in the form of CVID enteropathy. Based upon the clinical presentation and histopatholic findings the patient was diagnosed as CVID enteropathy and treated with intravenous antibiotics and 3-4 wkly intravenous immunoglobulin infusion and he had responded poorly to gastrointestinal symptoms but the frequency of respiratory and skin infection reduced. CVID has heterogenous gastrointestinal manifestations; among them the CVID enteropathy is an uncommon presentation which responds poorly to the mainstay therapy of intravenous immunoglobulin infusion and represents a diagnostic as well as therapeutic challenge for treating physician. PMID:22246610

  1. The serologic screening for celiac disease in the general population (blood donors) and in some high-risk groups of adults (patients with autoimmune diseases, osteoporosis and infertility) in the Czech republic.

    PubMed

    Vanciková, Z; Chlumecký, V; Sokol, D; Horáková, D; Hamsíková, E; Fucíková, T; Janatková, I; Ulcová-Gallová, Z; Stĕpán, J; Límanová, Z; Dvorák, M; Kocna, P; Sánchez, D; Tucková, L; Tlaskalová-Hogenová, H

    2002-01-01

    The prevalence of celiac disease (CD) was determined in healthy blood donors and in high-risk groups of adults (a total of 1835 adults--randomly selected 1312 healthy blood donors, 102 patients with primary osteoporosis, 58 patients with autoimmune diseases and 365 infertile women). It was calculated on the basis of a two-step serologic screening method--in the first step IgA and IgG antigliadin antibodies (AGA) and IgA anti-gamma-glutamyltransferase ('transglutaminase') antibodies (ATG) were estimated, in the second step sera positive for IgA AGA and/or IgA ATG were examined for antiendomysial IgA (AEA) antibodies. Immunoenzymic assay (ELISA) was used for determining of AGA and ATG antibodies; immunofluorescence method, performed on human umbilical cord tissue, was used for assaying of AEA antibodies. Total serum IgA level in only IgG AGA positive subjects was measured by routine turbidimetric method. 0.45% of healthy blood donors, 0.98% of osteoporotic patients, 2.7% of patients suffering from autoimmune disease and 1.13% of women with infertility considered as immunologically mediated were found to be positive in both steps of serologic screening (AGA and/or ATG and antiendomysium positive). The presumed high prevalence of seropositivity for CD in apparently healthy Czech adult population was confirmed. In the high-risk groups, the prevalence of seropositivity for CD was approximately 2-4 times higher than in healthy blood donors. The real prevalence of CD in the tested groups, however, can be estimated after performing small intestinal biopsy in the seropositive patients. PMID:12630332

  2. Comparisons of CVID and IgGSD: Referring Physicians, Autoimmune Conditions, Pneumovax Reactivity, Immunoglobulin Levels, Blood Lymphocyte Subsets, and HLA-A and -B Typing in 432 Adult Index Patients

    PubMed Central

    Barton, James C.; Bertoli, Luigi F.; Barton, J. Clayborn

    2014-01-01

    Common variable immunodeficiency (CVID) and immunoglobulin (Ig) G subclass deficiency (IgGSD) are heterogeneous disorders characterized by respiratory tract infections, selective Ig isotype deficiencies, and impaired antibody responses to polysaccharide antigens. Using univariable analyses, we compared observations in 34 CVID and 398 IgGSD adult index patients (81.9% women) referred to a hematology/oncology practice. Similarities included specialties of referring physicians, mean ages, proportions of women, reactivity to Pneumovax, median serum IgG3 and IgG4 levels, median blood CD56+/CD16+ lymphocyte levels, positivity for HLA-A and -B types, and frequencies of selected HLA-A, -B haplotypes. Dissimilarities included greater prevalence of autoimmune conditions, lower median IgG, IgA, and IgM, and lower median CD19+, CD3+/CD4+, and CD3+/CD8+ blood lymphocytes in CVID patients. Prevalence of Sjögren's syndrome and hypothyroidism was significantly greater in CVID patients. Combined subnormal IgG1/IgG3 occurred in 59% and 29% of CVID and IgGSD patients, respectively. Isolated subnormal IgG3 occurred in 121 IgGSD patients (88% women). Logistic regression on CVID (versus IgGSD) revealed a significant positive association with autoimmune conditions and significant negative associations with IgG1, IgG3, and IgA and CD56+/CD16+ lymphocyte levels, but the odds ratio was increased for autoimmune conditions alone (6.9 (95% CI 1.3, 35.5)). PMID:25295286

  3. Small Intestine Bacterial Overgrowth and Environmental Enteropathy in Bangladeshi Children

    PubMed Central

    Haque, Rashidul; Kirkpatrick, Beth D.; Alam, Masud; Lu, Miao; Kabir, Mamun; Kakon, Shahria Hafiz; Islam, Bushra Zarin; Afreen, Sajia; Musa, Abu; Khan, Shaila Sharmeen; Colgate, E. Ross; Carmolli, Marya P.; Ma, Jennie Z.

    2016-01-01

    ABSTRACT Recent studies suggest small intestine bacterial overgrowth (SIBO) is common among developing world children. SIBO’s pathogenesis and effect in the developing world are unclear. Our objective was to determine the prevalence of SIBO in Bangladeshi children and its association with malnutrition. Secondary objectives included determination of SIBO’s association with sanitation, diarrheal disease, and environmental enteropathy. We performed a cross-sectional analysis of 90 Bangladeshi 2-year-olds monitored since birth from an impoverished neighborhood. SIBO was diagnosed via glucose hydrogen breath testing, with a cutoff of a 12-ppm increase over baseline used for SIBO positivity. Multivariable logistic regression was performed to investigate SIBO predictors. Differences in concomitant inflammation and permeability between SIBO-positive and -negative children were compared with multiple comparison adjustment. A total of 16.7% (15/90) of the children had SIBO. The strongest predictors of SIBO were decreased length-for-age Z score since birth (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.03 to 0.60) and an open sewer outside the home (OR, 4.78; 95% CI, 1.06 to 21.62). Recent or frequent diarrheal disease did not predict SIBO. The markers of intestinal inflammation fecal Reg 1β (116.8 versus 65.6 µg/ml; P = 0.02) and fecal calprotectin (1,834.6 versus 766.7 µg/g; P = 0.004) were elevated in SIBO-positive children. Measures of intestinal permeability and systemic inflammation did not differ between the groups. These findings suggest linear growth faltering and poor sanitation are associated with SIBO independently of recent or frequent diarrheal disease. SIBO is associated with intestinal inflammation but not increased permeability or systemic inflammation. PMID:26758185

  4. The rabbit as an infection model for equine proliferative enteropathy.

    PubMed

    Sampieri, Francesca; Allen, Andrew L; Pusterla, Nicola; Vannucci, Fabio A; Antonopoulos, Aphroditi J; Ball, Katherine R; Thompson, Julie; Dowling, Patricia M; Hamilton, Don L; Gebhart, Connie J

    2013-04-01

    The objective of this study was to demonstrate the susceptibility of rabbits to Lawsonia intracellularis obtained from a case of clinical equine proliferative enteropathy (EPE). This is a preliminary step toward developing a rabbit infection model for studying pathogenesis and therapy of EPE in horses. Nine does were equally assigned to 3 groups. Animals in 2 groups (Group 1 and Group 2) were orally inoculated with different doses of cell-cultured L. intracellularis. Controls (Group 3) were sham-inoculated. Feces and blood were collected before the rabbits were infected and at 7, 14, and 21 days post-infection (DPI). Serum immunoglobulin G (IgG) titers were measured using an immunoperoxidase monolayer assay (IPMA) and fecal samples were analyzed with quantitative polymerase chain reaction (qPCR). A doe from each group was euthanized at 7, 14, and 21 DPI for collection and evaluation of intestinal samples. Tissues were stained by routine hematoxylin and eosin (H&E) method and immunohistochemistry (IHC) with L. intracellularis-specific mouse monoclonal antibody. At 14 DPI, serologic responses were detected in both infected groups, which maintained high titers through to 21 DPI. Lawsonia intracellularis DNA was detected in the feces of Group 2 on 7 DPI and in both infected groups on 14 DPI. Gross lesions were apparent in Group 1 and Group 2 on 14 DPI. Immunohistochemistry confirmed L. intracellularis antigen within cells of rabbits in Group 1 and Group 2 on 7, 14, and 21 DPI. No lesions, serologic response, shedding, or IHC labeling were found in Group 3 rabbits. This study describes an EPE rabbit model that simulates natural infection, as typical lesions, immune response, and fecal shedding were present. PMID:24082402

  5. The rabbit as an infection model for equine proliferative enteropathy

    PubMed Central

    Sampieri, Francesca; Allen, Andrew L.; Pusterla, Nicola; Vannucci, Fabio A.; Antonopoulos, Aphroditi J.; Ball, Katherine R.; Thompson, Julie; Dowling, Patricia M.; Hamilton, Don L.; Gebhart, Connie J.

    2013-01-01

    The objective of this study was to demonstrate the susceptibility of rabbits to Lawsonia intracellularis obtained from a case of clinical equine proliferative enteropathy (EPE). This is a preliminary step toward developing a rabbit infection model for studying pathogenesis and therapy of EPE in horses. Nine does were equally assigned to 3 groups. Animals in 2 groups (Group 1 and Group 2) were orally inoculated with different doses of cell-cultured L. intracellularis. Controls (Group 3) were sham-inoculated. Feces and blood were collected before the rabbits were infected and at 7, 14, and 21 days post-infection (DPI). Serum immunoglobulin G (IgG) titers were measured using an immunoperoxidase monolayer assay (IPMA) and fecal samples were analyzed with quantitative polymerase chain reaction (qPCR). A doe from each group was euthanized at 7, 14, and 21 DPI for collection and evaluation of intestinal samples. Tissues were stained by routine hematoxylin and eosin (H&E) method and immunohistochemistry (IHC) with L. intracellularis-specific mouse monoclonal antibody. At 14 DPI, serologic responses were detected in both infected groups, which maintained high titers through to 21 DPI. Lawsonia intracellularis DNA was detected in the feces of Group 2 on 7 DPI and in both infected groups on 14 DPI. Gross lesions were apparent in Group 1 and Group 2 on 14 DPI. Immunohistochemistry confirmed L. intracellularis antigen within cells of rabbits in Group 1 and Group 2 on 7, 14, and 21 DPI. No lesions, serologic response, shedding, or IHC labeling were found in Group 3 rabbits. This study describes an EPE rabbit model that simulates natural infection, as typical lesions, immune response, and fecal shedding were present. PMID:24082402

  6. Comparison of different methods for diagnosis of porcine proliferative enteropathy

    PubMed Central

    Guedes, Roberto M.C.; Gebhart, Connie J.; Winkelman, Nathan L.; Mackie-Nuss, Rebecca A.C.; Marsteller, Thomas A.; Deen, John

    2002-01-01

    The objectives of this study were: (1) to compare 2 methods of serology; (2) to compare 3 histologic techniques; and (3) to compare 2 methods of detecting shedding in pigs experimentally challenged with Lawsonia intracellularis. The sensitivities of these tests were determined by the detection of infection. Forty 5-week-old pigs were inoculated on day 0 with intestinal homogenate from pigs with proliferative enteropathy (PE). Clinical evaluation was done on day 7 and daily from day 14 to 28 postinoculation. Fecal shedding of L. intracellularis was monitored by use of polymerase chain reaction (PCR) analysis and immunoperoxidase staining at 7-day intervals. Serum was obtained on days 0 and 28 for serologic testing by glass slide and tissue culture indirect fluorescent antibody tests. At euthanasia on day 28, gross intestinal lesions were evaluated and ileum samples collected for histologic analyses. Ileal histologic sections from each animal were stained by hematoxylin and eosin, Warthin-Starry silver stain, and immunohistochemistry (IHC). Of the 40 pigs, 36 had gross lesions typical of PE at necropsy. The percentage of agreement between the 2 serologic methods was 94.4%. Immunoperoxidase stain of fecal smears was more sensitive than PCR for detecting fecal shedding, especially on day 21 (89.5% and 60.5%, respectively) and day 28 (59.4% and 37.5%, respectively) post-inoculation. The IHC stain was much more sensitive for detecting infection than the routinely used hematoxylin and eosin and Warthin-Starry silver stains. In conclusion, in experimentally infected pigs, both serologic methods were appropriate techniques for detecting infection. For fecal samples, PCR has low sensitivity. Immunohistochemistry is the best diagnostic tool for formalin-fixed samples. PMID:11989741

  7. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2016-04-22

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

  8. Environmental Basis of Autoimmunity.

    PubMed

    Floreani, Annarosa; Leung, Patrick S C; Gershwin, M Eric

    2016-06-01

    The three common themes that underlie the induction and perpetuation of autoimmunity are genetic predisposition, environmental factors, and immune regulation. Environmental factors have gained much attention for their role in triggering autoimmunity, with increasing evidence of their influence as demonstrated by epidemiological studies, laboratory research, and animal studies. Environmental factors known to trigger and perpetuate autoimmunity include infections, gut microbiota, as well as physical and environmental agents. To address these issues, we will review major potential mechanisms that underlie autoimmunity including molecular mimicry, epitope spreading, bystander activation, polyclonal activation of B and T cells, infections, and autoinflammatory activation of innate immunity. The association of the gut microbiota on autoimmunity will be particularly highlighted by their interaction with pharmaceutical agents that may lead to organ-specific autoimmunity. Nonetheless, and we will emphasize this point, the precise mechanism of environmental influence on disease pathogenesis remains elusive. PMID:25998909

  9. The use of infliximab in X-linked agammaglobulinaemia associated enteropathy.

    PubMed

    Davey, P T; Tan, C J; Gardiner, K

    2014-07-01

    Granulomatous small bowel enteropathy is an unusual presentation associated with X-linked agammaglobulinaemia. We present a rare case of this condition that was further complicated by an enterocutaneous fistula and report our experience managing this condition successfully with infliximab, which has not been documented in the literature previously. PMID:24992401

  10. Diagnostic and epidemiological features of Lawsonia intracellularis enteropathy in 2 foals

    PubMed Central

    Dauvillier, Julie; Picandet, Valérie; Harel, Josée; Gottschalk, Marcelo; Desrosiers, Robert; Jean, Daniel; Lavoie, Jean-Pierre

    2006-01-01

    Abstract Two clinical cases of equine proliferative enteropathy are described. Both foals had a positive fecal polymerase chain reaction, but shedding of the bacterium stopped < 4 days after therapy was initiated. One foal was serologically positive 3 days after onset of clinical signs and remained positive for more than 6 months. PMID:16898113

  11. Expression Pattern of Fatty Acid Binding Proteins in Celiac Disease Enteropathy

    PubMed Central

    Bottasso Arias, Natalia M.; García, Marina; Bondar, Constanza; Guzman, Luciana; Redondo, Agustina; Chopita, Nestor; Córsico, Betina; Chirdo, Fernando G.

    2015-01-01

    Celiac disease (CD) is an immune-mediated enteropathy that develops in genetically susceptible individuals following exposure to dietary gluten. Severe changes at the intestinal mucosa observed in untreated CD patients are linked to changes in the level and in the pattern of expression of different genes. Fully differentiated epithelial cells express two isoforms of fatty acid binding proteins (FABPs): intestinal and liver, IFABP and LFABP, respectively. These proteins bind and transport long chain fatty acids and also have other important biological roles in signaling pathways, particularly those related to PPARγ and inflammatory processes. Herein, we analyze the serum levels of IFABP and characterize the expression of both FABPs at protein and mRNA level in small intestinal mucosa in severe enteropathy and normal tissue. As a result, we observed higher levels of circulating IFABP in untreated CD patients compared with controls and patients on gluten-free diet. In duodenal mucosa a differential FABPs expression pattern was observed with a reduction in mRNA levels compared to controls explained by the epithelium loss in severe enteropathy. In conclusion, we report changes in FABPs' expression pattern in severe enteropathy. Consequently, there might be alterations in lipid metabolism and the inflammatory process in the small intestinal mucosa. PMID:26346822

  12. Zinc or albendazole attenuates the progression of environmental enteropathy a randomized controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Environmental enteropathy (EE) is a subclinical condition among children in the developing world, characterized by T-cell infiltration of the small-bowel mucosa and diffuse villous atrophy. EE leads to macronutrient and micronutrient malabsorption and stunting, with a resultant increased risk for in...

  13. Genome Sequence of Lawsonia intracellularis Strain N343, Isolated from a Sow with Hemorrhagic Proliferative Enteropathy.

    PubMed

    Sait, Michelle; Aitchison, Kevin; Wheelhouse, Nick; Wilson, Kim; Lainson, F Alex; Longbottom, David; Smith, David G E

    2013-01-01

    Lawsonia intracellularis is the etiological agent of proliferative enteropathy (PE), causing mild or acute hemorrhagic diarrhea in infected animals. Here we report the genome sequence of strain N343, isolated from a sow that died of hemorrhagic PE. N343 contains 24 single nucleotide polymorphisms and 90 indels compared to the reference strain PHE/MN1-00. PMID:23472224

  14. Genome Sequence of Lawsonia intracellularis Strain N343, Isolated from a Sow with Hemorrhagic Proliferative Enteropathy

    PubMed Central

    Sait, Michelle; Aitchison, Kevin; Wheelhouse, Nick; Wilson, Kim; Lainson, F. Alex; Longbottom, David

    2013-01-01

    Lawsonia intracellularis is the etiological agent of proliferative enteropathy (PE), causing mild or acute hemorrhagic diarrhea in infected animals. Here we report the genome sequence of strain N343, isolated from a sow that died of hemorrhagic PE. N343 contains 24 single nucleotide polymorphisms and 90 indels compared to the reference strain PHE/MN1-00. PMID:23472224

  15. Expression Pattern of Fatty Acid Binding Proteins in Celiac Disease Enteropathy.

    PubMed

    Bottasso Arias, Natalia M; García, Marina; Bondar, Constanza; Guzman, Luciana; Redondo, Agustina; Chopita, Nestor; Córsico, Betina; Chirdo, Fernando G

    2015-01-01

    Celiac disease (CD) is an immune-mediated enteropathy that develops in genetically susceptible individuals following exposure to dietary gluten. Severe changes at the intestinal mucosa observed in untreated CD patients are linked to changes in the level and in the pattern of expression of different genes. Fully differentiated epithelial cells express two isoforms of fatty acid binding proteins (FABPs): intestinal and liver, IFABP and LFABP, respectively. These proteins bind and transport long chain fatty acids and also have other important biological roles in signaling pathways, particularly those related to PPARγ and inflammatory processes. Herein, we analyze the serum levels of IFABP and characterize the expression of both FABPs at protein and mRNA level in small intestinal mucosa in severe enteropathy and normal tissue. As a result, we observed higher levels of circulating IFABP in untreated CD patients compared with controls and patients on gluten-free diet. In duodenal mucosa a differential FABPs expression pattern was observed with a reduction in mRNA levels compared to controls explained by the epithelium loss in severe enteropathy. In conclusion, we report changes in FABPs' expression pattern in severe enteropathy. Consequently, there might be alterations in lipid metabolism and the inflammatory process in the small intestinal mucosa. PMID:26346822

  16. Hydrogen sulphide protects against NSAID-enteropathy through modulation of bile and the microbiota

    PubMed Central

    Blackler, Rory W; Motta, Jean-Paul; Manko, Anna; Workentine, Matthew; Bercik, Premysl; Surette, Michael G; Wallace, John L

    2015-01-01

    Background and Purpose Hydrogen sulphide is an important mediator of gastrointestinal mucosal defence. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is significantly limited by their toxicity in the gastrointestinal tract. Particularly concerning is the lack of effective preventative or curative treatments for NSAID-induced intestinal damage and bleeding. We evaluated the ability of a hydrogen sulphide donor to protect against NSAID-induced enteropathy. Experimental Approach Intestinal ulceration and bleeding were induced in Wistar rats by oral administration of naproxen. The effects of suppression of endogenous hydrogen sulphide synthesis or administration of a hydrogen sulphide donor (diallyl disulphide) on naproxen-induced enteropathy was examined. Effects of diallyl disulphide on small intestinal inflammation and intestinal microbiota were also assessed. Bile collected after in vivo naproxen and diallyl disulphide administration was evaluated for cytotoxicity in vitro using cultured intestinal epithelial cells. Key Results Suppression of endogenous hydrogen sulphide synthesis by β-cyano-L-alanine exacerbated naproxen-induced enteropathy. Diallyl disulphide co-administration dose-dependently reduced the severity of naproxen-induced small intestinal damage, inflammation and bleeding. Diallyl disulphide administration attenuated naproxen-induced increases in the cytotoxicity of bile on cultured enterocytes, and prevented or reversed naproxen-induced changes in the intestinal microbiota. Conclusions and Implications Hydrogen sulphide protects against NSAID-enteropathy in rats, in part reducing the cytotoxicity of bile and preventing NSAID-induced dysbiosis. PMID:25297699

  17. Autoimmune liver disease, autoimmunity and liver transplantation.

    PubMed

    Carbone, Marco; Neuberger, James M

    2014-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune

  18. Heparanase and Autoimmune Diabetes

    PubMed Central

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

    2013-01-01

    Heparanase (Hpse) is the only known mammalian endo-β-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

  19. Metals and kidney autoimmunity.

    PubMed Central

    Bigazzi, P E

    1999-01-01

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

  20. American Autoimmune Related Diseases Association

    MedlinePlus

    ... With #25FOR25 Campaign During National Autoimmune Disease Awareness Month AARDA officially kicks of National Autoimmune DIsease Awareness ... Click here to read more. Autoimmune Disease Awareness Month AARDA and the NCAPG held two important events ...

  1. Activation of nuclear factor-kappaB in dogs with chronic enteropathies.

    PubMed

    Luckschander, Nicole; Hall, Jean A; Gaschen, Frédéric; Forster, Ursula; Wenzlow, Nanny; Hermann, Pascal; Allenspach, Karin; Dobbelaere, Dirk; Burgener, Iwan A; Welle, Monika

    2010-02-15

    Homeostasis in the intestinal microenvironment between the immune system and luminal antigens appears disturbed in chronic enteropathies. Pro-inflammatory cytokines likely play a role in the pathogenesis of intestinal inflammation. Several inflammatory and immunoregulatory genes have associated nuclear factor-kappaB (NF-kappaB) binding sites, which allow NF-kappaB to regulate gene transcription. The purpose of this study was to investigate (1) the occurrence of NF-kappaB activation during mucosal inflammation in situ, (2) the mucosal distribution pattern of cells expressing activated NF-kappaB within treatment groups, and (3) the effect of specific therapy on NF-kappaB activation. Dogs with chronic enteropathy were studied (n=26) and compared with 13 healthy dogs. Ten dogs had food responsive disease (FRD) and 16 had inflammatory bowel disease (IBD). NF-kappaB activation was detected in duodenal mucosal biopsies using a mouse monoclonal antibody (MAB 3026) that selectively binds the nuclear localization sequence of activated NF-kappaB. To identify macrophages, biopsies were stained using the MAC 387 antibody. Macrophages in the lamina propria double-stained for MAC 387 and NF-kappaB were quantitated; epithelial cell expression of activated NF-kappaB was determined semi-quantitatively. Results showed that more macrophages positive for activated NF-kappaB were present in lamina propria of dogs with chronic enteropathy compared to control dogs (p<0.01). More NF-kappaB positive epithelial cells were observed in FRD dogs compared to IBD dogs (p<0.05). After therapy, the number of macrophages and epithelial cells staining positive for activated NF-kappaB decreased (p<0.01) in chronic enteropathy dogs. In conclusion, activation of NF-kappaB is closely associated with the pathophysiology of canine chronic enteropathy. Down-regulation follows successful therapy. PMID:19740552

  2. The Autoimmune Ecology

    PubMed Central

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

    2016-01-01

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

  3. The Autoimmune Ecology.

    PubMed

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

    2016-01-01

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

  4. Genetic basis of autoimmunity

    PubMed Central

    Marson, Alexander; Housley, William J.; Hafler, David A.

    2015-01-01

    Autoimmune diseases affect up to approximately 10% of the population. While rare Mendelian autoimmunity syndromes can result from monogenic mutations disrupting essential mechanisms of central and peripheral tolerance, more common human autoimmune diseases are complex disorders that arise from the interaction between polygenic risk factors and environmental factors. Although the risk attributable to most individual nucleotide variants is modest, genome-wide association studies (GWAS) have the potential to provide an unbiased view of biological pathways that drive human autoimmune diseases. Interpretation of GWAS requires integration of multiple genomic datasets including dense genotyping, cis-regulatory maps of primary immune cells, and genotyped studies of gene expression in relevant cell types and cellular conditions. Improved understanding of the genetic basis of autoimmunity may lead to a more sophisticated understanding of underlying cellular phenotypes and, eventually, novel diagnostics and targeted therapies. PMID:26030227

  5. Autoimmune autonomic disorders.

    PubMed

    Mckeon, Andrew; Benarroch, Eduardo E

    2016-01-01

    Autoimmune autonomic disorders occur because of an immune response directed against sympathetic, parasympathetic, and enteric ganglia, autonomic nerves, or central autonomic pathways. In general, peripheral autoimmune disorders manifest with either generalized or restricted autonomic failure, whereas central autoimmune disorders manifest primarily with autonomic hyperactivity. Some autonomic disorders are generalized, and others are limited in their anatomic extent, e.g., isolated gastrointestinal dysmotility. Historically, these disorders were poorly recognized, and thought to be neurodegenerative. Over the last 20 years a number of autoantibody biomarkers have been discovered that have enabled the identification of certain patients as having an autoimmune basis for either autonomic failure or hyperactivity. Peripheral autoimmune autonomic disorders include autoimmune autonomic ganglionopathy (AAG), paraneoplastic autonomic neuropathy, and acute autonomic and sensory neuropathy. AAG manifests with acute or subacute onset of generalized or selective autonomic failure. Antibody targeting the α3 subunit of the ganglionic-type nicotinic acetylcholine receptor (α3gAChR) is detected in approximately 50% of cases of AAG. Some other disorders are characterized immunologically by paraneoplastic antibodies with a high positive predictive value for cancer, such as antineuronal nuclear antibody, type 1 (ANNA-1: anti-Hu); others still are seronegative. Recognition of an autoimmune basis for autonomic disorders is important, as their manifestations are disabling, may reflect an underlying neoplasm, and have the potential to improve with a combination of symptomatic and immune therapies. PMID:27112689

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

    PubMed Central

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

    2015-01-01

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

  7. HTLV-1, Immune Response and Autoimmunity

    PubMed Central

    Quaresma, Juarez A S; Yoshikawa, Gilberto T; Koyama, Roberta V L; Dias, George A S; Fujihara, Satomi; Fuzii, Hellen T

    2015-01-01

    Human T-lymphotropic virus type-1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATL). Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM) is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Sjögren’s Syndrome (SS). The development of HTLV-1-driven autoimmunity is hypothesized to rely on molecular mimicry, because virus-like particles can trigger an inflammatory response. However, HTLV-1 modifies the behavior of CD4+ T cells on infection and alters their cytokine production. A previous study showed that in patients infected with HTLV-1, the activity of regulatory CD4+ T cells and their consequent expression of inflammatory and anti-inflammatory cytokines are altered. In this review, we discuss the mechanisms underlying changes in cytokine release leading to the loss of tolerance and development of autoimmunity. PMID:26712781

  8. Commensal microbiota influence systemic autoimmune responses

    PubMed Central

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

    2015-01-01

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

  9. Autoimmunity in picornavirus infections.

    PubMed

    Massilamany, Chandirasegaran; Koenig, Andreas; Reddy, Jay; Huber, Sally; Buskiewicz, Iwona

    2016-02-01

    Enteroviruses are small, non-enveloped, positive-sense single-strand RNA viruses, and are ubiquitously found throughout the world. These viruses usually cause asymptomatic or mild febrile illnesses, but have a propensity to induce severe diseases including type 1 diabetes and pancreatitis, paralysis and neuroinflammatory disease, myocarditis, or hepatitis. This pathogenicity may result from induction of autoimmunity to organ-specific antigens. While enterovirus-triggered autoimmunity can arise from multiple mechanisms including antigenic mimicry and release of sequestered antigens, the recent demonstration of T cells expressing dual T cell receptors arising as a natural consequence of Theiler's virus infection is the first demonstration of this autoimmune mechanism. PMID:26554915

  10. [Gluten-sensitive enteropathy with intestinal T-cell lymphoma: an unusual cause of in disabling osteomalacia].

    PubMed

    Rösler, D; Beyeler, C; Borisch, B; Olah, A; Inauen, W; Gerber, N J

    1995-10-01

    We describe a 64-year-old woman with a malignant intestinal T-cell lymphoma who presented four years later with disabling osteomalacia and secondary hyperparathyroidism due to malabsorption. Only two years later, when the patient had developed fatty stools, flatulence and weight loss, diagnosis of gluten-sensitive enteropathy (GSE) was confirmed by small-intestine biopsy. This case report illustrates that in adults GSE can be oligosymptomatic for long periods. In cases of osteomalacia or rare intestinal T-cell lymphoma a detailed history of bowel movements, inspection of stools, quantification of fat excretion in stools and laboratory tests for malabsorption are recommended. Positive antibodies against gliadin, endomysium and reticulin may support the diagnosis of GSE. However, intestinal biopsy is necessary to verify the presence of GSE. In view of the unspecific histological changes, a follow-up biopsy is recommended in oligosymptomatic cases. Serial measurements of antibodies allow supervision of compliance for a diet strictly free of gluten. In addition, lactose containing milk products need to be restricted initially because of secondary lactase deficiency. PMID:7481645

  11. Autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: analysis of 533 adult patients who underwent transplantation at King's College Hospital.

    PubMed

    Wang, Meng; Wang, Wenjia; Abeywardane, Ayesha; Adikarama, Malinthi; McLornan, Donal; Raj, Kavita; de Lavallade, Hugues; Devereux, Stephen; Mufti, Ghulam J; Pagliuca, Antonio; Potter, Victoria T; Mijovic, Aleksandar

    2015-01-01

    Autoimmune hemolytic anemia (AIHA) is a recognized complication of hematopoietic stem cell transplantation (HSCT); it is often refractory to treatment and carries a high mortality. To improve understanding of the incidence, risk factors, and clinical outcome of post-transplantation AIHA, we analyzed 533 patients who received allogeneic HSCT, and we identified 19 cases of AIHA after HSCT (overall incidence, 3.6%). The median time to onset, from HSCT to AIHA, was 202 days. AIHA was associated with HSCT from unrelated donors (hazard ratio [HR], 5.28; 95% confidence interval [CI], 1.22 to 22.9; P = .026). In the majority (14 of 19; 74%) of AIHA patients, multiple agents for treatment were required, with only 9 of 19 (47%) patients achieving complete resolution of AIHA. Patients with post-transplantation AIHA had a higher overall mortality (HR, 2.48; 95% CI, 1.33 to 4.63; P = .004), with 36% (4 of 11 cases) of deaths attributable to AIHA. PMID:25262883

  12. Autoimmune liver disease panel

    MedlinePlus

    ... common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care ... anti-mitochondrial antibodies, you are likely to have primary biliary cirrhosis. If the immune proteins are high and albumin ...

  13. Understanding Autoimmune Diseases

    MedlinePlus

    ... Autoimmune Diseases Progress and Promise Key Words The Immune System Your immune system is the network of cells and tissues throughout ... having two parts: the acquired and the innate immune systems. The acquired (or adaptive) immune system develops as ...

  14. Autoimmune Autonomic Ganglionopathy

    MedlinePlus

    ... usf.edu/ARDCRC/professional/register/index.htm Organizations Organizations Listen Nonprofit support and advocacy groups bring together ... endorsement by GARD. Suggest an organization to add. Organizations Supporting this Disease American Autoimmune Related Diseases Association ( ...

  15. Cows' milk protein-sensitive enteropathy. Combined clinical and histological criteria for diagnosis.

    PubMed Central

    Iyngkaran, N; Robinson, M J; Prathap, K; Sumithran, E; Yadav, M

    1978-01-01

    Cows' milk protein enteropathy is recognised as a significant cause of persistent diarrhoea and malabsorption in young infants, but there are as yet no generally accepted diagnostic criteria. A combined clinical and histological approach to the diagnosis of cows' milk protein-sensitive enteropathy has been used in 15 patients, and the following set of criteria are proposed. (1) Clinical disease (diarrhoea with or without vomiting) while receiving cows' milk protein. (2) Clinical improvement on a diet free of cows' milk protein. (3) Normal or mildly abnormal histology of jejunal mucosa when taken 6-8 weeks after symptoms subside. (4) Histological relapse, with or without clinical relapse, after re-exposure to cows' milk protein. Images Fig. 1 Fig. 2 PMID:564668

  16. Autoimmunity in 2014.

    PubMed

    Selmi, Carlo

    2015-10-01

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

  17. Silica, Silicosis, and Autoimmunity

    PubMed Central

    Pollard, Kenneth Michael

    2016-01-01

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

  18. Silica, Silicosis, and Autoimmunity.

    PubMed

    Pollard, Kenneth Michael

    2016-01-01

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

  19. Opportunistic autoimmune disorders

    PubMed Central

    Kong, Yi-chi M.; Wei, Wei-Zen; Tomer, Yaron

    2013-01-01

    Rapid advances in our understanding of the immune network have led to treatment modalities for malignancies and autoimmune diseases based on modulation of the immune response. Yet therapeutic modulation has resulted in immune dysregulation and opportunistic autoimmune sequelae, despite prescreening efforts in clinical trials. This review focuses on recent clinical data on opportunistic autoimmune disorders arising from three immunotherapeutic modalities: (1) systemic immunomodulators, including interferon-α (also used to treat hepatitis C patients) and interferon-β; (2) monoclonal antibodies to CTLA-4 and CD52, and (3) hematopoietic stem cell transplantation. Uncategorized predisposing factors in these patients include major histocompatibility complex and gender genetics, prevalence of different autoimmune diseases, prior chemotherapy, underlying disorder (e.g., hepatitis C), and preconditioning regimens as part of organ and stem cell transplants. Not unexpectedly, the prevalent autoimmune thyroid disease surfaced frequently. Our combination models to study the balance between thyroid autoimmunity and tumor immunity upon regulatory T-cell perturbation are briefly described. PMID:20146718

  20. Autoimmunity in 2013.

    PubMed

    Selmi, Carlo

    2014-08-01

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

  1. Thoracic Duct Decompression for Protein-Losing Enteropathy in Failing Fontan Circulation.

    PubMed

    António, Marta; Gordo, Andreia; Pereira, Conceição; Pinto, Fátima; Fragata, Isabel; Fragata, José

    2016-06-01

    An infrequent but devastating late complication of Fontan circulation is protein-losing enteropathy (PLE), which results from unbalanced lymphatic homeostasis. Surgical decompression of the thoracic duct by redirecting its drainage to the pulmonary venous atrium has been introduced recently as a possible treatment. This report describes a single-institution experience with this innovative procedure in 2 patients with failing Fontan circulation with PLE refractory to optimized medical therapy. PMID:27211948

  2. Seizures Associated With Hypocalcemia in a Yorkshire Terrier With Protein-Losing Enteropathy.

    PubMed

    Whitehead, Jim; Quimby, Jessica; Bayliss, Danielle

    2015-01-01

    A 7 yr old, male, castrated, Yorkshire terrier was presented on emergency for an acute onset of seizure activity. The owner also reported that the dog had previously exhibited other symptoms, including intermittent vomiting, diarrhea, and anorexia for several yr. The initial workup revealed a marked decrease in ionized calcium and total protein. Further diagnostics revealed decreases in magnesium, 25 hydroxyvitamin D, albumin, and globulins, and an increased parathyroid hormone level. Intestinal biopsies revealed inflammatory bowel disease and lymphangiectasia. The dog received intravenous calcium gluconate for treatment of hypocalcemia followed by oral calcium and vitamin D supplementation. Seizure activity ceased once calcium levels approached the normal range. Medical and dietary therapy for lymphangiectasia and inflammatory bowel disease consisted of prednisone, rutin, and a low-fat diet. Decreased serum total ionized calcium levels have been reported previously in dogs with protein-losing enteropathies. Typically, the hypocalcemia is not associated with clinical signs. Severe clinical signs of hypocalcemia are rarely reported in dogs with protein-losing enteropathy, but seizures, facial twitching, and tremors can occur. When presented with a dog with a history of seizure activity, panhypoproteinemia, and hypocalcemia, protein-losing enteropathy should be included on the list of differential diagnoses. PMID:26535456

  3. Coniferyl Aldehyde Attenuates Radiation Enteropathy by Inhibiting Cell Death and Promoting Endothelial Cell Function

    PubMed Central

    Son, Yeonghoon; Jang, Jun-Ho; Lee, Yoon-Jin; Kim, Sung-Ho; Ko, Young-Gyo; Lee, Yun-Sil; Lee, Hae-June

    2015-01-01

    Radiation enteropathy is a common complication in cancer patients. The aim of this study was to investigate whether radiation-induced intestinal injury could be alleviated by coniferyl aldehyde (CA), an HSF1-inducing agent that increases cellular HSP70 expression. We systemically administered CA to mice with radiation enteropathy following abdominal irradiation (IR) to demonstrate the protective effects of CA against radiation-induced gastrointestinal injury. CA clearly alleviated acute radiation-induced intestinal damage, as reflected by the histopathological data and it also attenuated sub-acute enteritis. CA prevented intestinal crypt cell death and protected the microvasculature in the lamina propria during the acute and sub-acute phases of damage. CA induced HSF1 and HSP70 expression in both intestinal epithelial cells and endothelial cells in vitro. Additionally, CA protected against not only the apoptotic cell death of both endothelial and epithelial cells but also the loss of endothelial cell function following IR, indicating that CA has beneficial effects on the intestine. Our results provide novel insight into the effects of CA and suggest its role as a therapeutic candidate for radiation-induced enteropathy due to its ability to promote rapid re-proliferation of the intestinal epithelium by the synergic effects of the inhibition of cell death and the promotion of endothelial cell function. PMID:26029925

  4. Autoimmunity and Asbestos Exposure

    PubMed Central

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

    2014-01-01

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

  5. Autoimmune basal ganglia disorders.

    PubMed

    Dale, Russell C; Brilot, Fabienne

    2012-11-01

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

  6. Experimental Autoimmune Breast Failure

    PubMed Central

    Kesaraju, Pavani; Jaini, Ritika; Johnson, Justin M.; Altuntas, Cengiz Z.; Gruden, Jessica J.; Sakalar, Cagri; Tuohy, Vincent K.

    2013-01-01

    Mastitis is a substantial clinical problem in lactating women that may result in severe pain and abrupt termination of breastfeeding, thereby predisposing infants to long-term health risks. Many cases of mastitis involve no known infectious agent and may fundamentally be due to autoimmune-mediated inflammation of the breast. Herein, we develop a murine model of autoimmune mastitis and provide a detailed characterization of its resulting phenotype of breast failure and lactation insufficiency. To generate breast-specific autoimmunity, we immunized SWXJ mice with recombinant mouse α-lactalbumin, a lactation-dependent, breast-specific differentiation protein critical for production of lactose. Mice immunized with α-lactalbumin showed extensive T-cell–mediated inflammation in lactating normal breast parenchyma but none in nonlactating normal breast parenchyma. This targeted autoimmune attack resulted in breast failure characterized by lactation insufficiency and decreased ability to nurture offspring. Although immunization with α-lactalbumin had no effect on fertility and birth numbers, pups nursed by α-lactalbumin–immunized mice showed significantly disrupted growth often accompanied by kwashiorkor-like nutritional abnormalities, including alopecia, liver toxicity, and runting. This experimental model of autoimmune breast failure has useful applications for prophylactic breast cancer vaccination and for addressing inflammatory complications during breastfeeding. In addition, this model is suited for investigating nutritionally based “failure-to-thrive” issues, particularly regarding the long-term implications of postnatal nutritional deprivation. PMID:22901749

  7. Reconceiving autoimmunity: An overview.

    PubMed

    Tauber, Alfred I

    2015-06-21

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

  8. Pregnancy with autoimmune hepatitis

    PubMed Central

    Braga, António Costa; Vasconcelos, Carlos; Braga, Jorge

    2016-01-01

    Aim: The aim of this study was to review our experience with gestations in autoimmune hepatitis patients. Background: There are only limited data describing pregnancy in patients with autoimmune hepatitis. Patients and methods: Retrospective analysis of pregnancies with autoimmune hepatitis followed in Centro Hospitalar do Porto, Portugal in the last ten years. Results: We reported nine pregnancies in seven patients with autoimmune hepatitis. Two patients had documented liver cirrhosis prior to the pregnancy. In this study, 66.7% of patients were treated with azathioprine and 88.9% with prednisolone. Clinical improvements were observed in 11.1% of pregnancies and 22.2% exacerbations were diagnosed. There were six live births and two preterm deliveries (preterm delivery rate of 33%). We also report three first trimester miscarriages (early gestation miscarriage rate of 33%). There were no neonatal or maternal deaths. Conclusion: The favorable obstetric outcome is a realistic expectation in patients with autoimmune hepatitis. Tight monitoring and control of asymptomatic and unpredictable exacerbations, which are unrelated to the severity of the underlying disease, are essential to the prognosis of the current pregnancy. PMID:27458515

  9. Epigenetics and Autoimmune Diseases

    PubMed Central

    Quintero-Ronderos, Paula; Montoya-Ortiz, Gladis

    2012-01-01

    Epigenetics is defined as the study of all inheritable and potentially reversible changes in genome function that do not alter the nucleotide sequence within the DNA. Epigenetic mechanisms such as DNA methylation, histone modification, nucleosome positioning, and microRNAs (miRNAs) are essential to carry out key functions in the regulation of gene expression. Therefore, the epigenetic mechanisms are a window to understanding the possible mechanisms involved in the pathogenesis of complex diseases such as autoimmune diseases. It is noteworthy that autoimmune diseases do not have the same epidemiology, pathology, or symptoms but do have a common origin that can be explained by the sharing of immunogenetic mechanisms. Currently, epigenetic research is looking for disruption in one or more epigenetic mechanisms to provide new insights into autoimmune diseases. The identification of cell-specific targets of epigenetic deregulation will serve us as clinical markers for diagnosis, disease progression, and therapy approaches. PMID:22536485

  10. EBV and Autoimmunity.

    PubMed

    Ascherio, Alberto; Munger, Kassandra L

    2015-01-01

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

  11. Autoimmunity in 2015.

    PubMed

    Selmi, Carlo

    2016-08-01

    Compared to the clear trend observed in previous years, the number of peer-reviewed articles published during 2015 and retrieved using the "autoimmunity" key word declined by 4 %, while remaining 5 % of immunology articles. On the other hand, a more detailed analysis of the published articles in leading immunology and autoimmunity journals revealed exciting scenarios, with fascinating lines of evidence being supported by convincing data and likely followed by rapid translational or clinical developments. As examples, the study of the microbiome, the development of new serum or other tissue biomarkers, and a more solid understanding of disease pathogenesis and tolerance breakdown mechanisms have been central issues in the past year. Furthermore and similar to the oncology field, progress in the understanding of single autoimmune condition is becoming most specific with psoriatic and rheumatoid arthritis being ideal paradigms with treatment options diverging after decades of common therapies, as illustrated by IL17-targeting approaches. The ultimate result of these advances is towards personalized medicine with an ideal approach being tailored on a single patient, based on a finely tuned definition of the immunogenetics, epigenetics, microbiome, and biomarkers. Finally, experimental reports suggest that cancer-associated immune mechanisms or the role of T and B cell subpopulations should be better understood in autoimmune diseases. While we hailed the 2014 literature in the autoimmunity world as part of an annus mirabilis, we should not be mistaken in the strong stimulus of research in autoimmunity represented by the 2015 articles that will be summarized in this article. PMID:27422713

  12. Perturbed zinc homeostasis in rural 3-5-y-old Malawian children is associated with abnormalities in intestinal permeability attributed to tropical enteropathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tropical enteropathy and zinc deficiency are major public health problems worldwide. Tropical enteropathy is characterized by reduced mannitol absorption with normal or increased lactulose absorption when a dual sugar absorption test is administered, the results of which are reported as the lactulos...

  13. Autoimmunity in Addison's disease.

    PubMed

    Martín Martorell, P; Roep, B O; Smit, J W A; Martorell, P M

    2002-08-01

    Addison's disease has a low incidence and is most frequently the result of an autoimmune disease in developed countries. Addison's disease can present as an isolated entity or in combination with other autoimmune diseases: Addison's disease can be part of the distinct polyglandular autoimmune syndromes APS I and II. Autoantibodies in patients with isolated Addison's disease are directed against the enzymes involved in steroid synthesis, P45oc21, P45oscc and P45oc17. Addison's disease, both isolated and in the context of APS II, has been associated with the haplotype HLA-A1, -B8 and DR3. The value of the increased expression of these molecules on adrenocortical cells could point towards an infectious pathogenesis. Given the prevalence, up to 80 %, of autoantibodies in Addison's disease as well as the high predictive value for developing the disease when antibodies are present (41% in three years), we advise screening high-risk populations, such as patients with other autoimmune endocrinopathies or their relatives for the presence of these antibodies. The adrenocortical function of patients positive for antibodies should be followed yearly. PMID:12430572

  14. Protein-losing enteropathy associated with refractory systemic lupus erythematosus with a good response to rituximab.

    PubMed

    Sansinanea, Pierina; Carrica, Sebastián Augusto; Marcos, Josefina; García, Mercedes Argentina

    2016-01-01

    A case is presented of a protein-losing enteropathy (PLE) as the initial manifestation of systemic lupus erythematosus (SLE) in a 17 year-old female patient, who presented with ascites, edema and hypoalbuminemia. The diagnosis of SLE was based on the presence of: malar rash, oral ulcers, thrombocytopenia, antinuclear antibodies, IgM anticardiolipin antibody, and lupus anticoagulant. Renal and liver diseases were ruled out. The PLE diagnosis was confirmed with fecal alpha 1-antitrypsin clearance. The PLE was refractory to different lines of immunosuppressive agents like glucocorticoids, cyclophosphamide, azathioprine, and cyclosporine, showing a satisfactory and sustained response with rituximab, allowing steroid sparing and long term remission. PMID:25818375

  15. Late post liver transplant protein losing enteropathy: Rare complication of incisional hernia

    PubMed Central

    Evans, Jonathan D; Perera, M Thamara PR; Pal, CY; Neuberger, James; Mirza, Darius F

    2013-01-01

    Development of oedema and hypoproteinaemia in a liver transplant recipient may be the first signs of graft dysfunction and should prompt a full assessment. We report the novel case of a patient who, years after liver transplantation developed a functional blind loop in an incisional hernia, which manifested as oedema and hypoproteinaemia secondary to protein losing enteropathy. After numerous investigations, the diagnosis was made by flurodeoxyglucose positron emmision tomography (FDG-PET) imaging. Surgical repair of the incisional hernia was followed several months later by resolution of the protein loss, and confirmed at a post operative FDG-PET scan at one year. PMID:23885154

  16. Exploring the role of environmental enteropathy in malnutrition, infant development and oral vaccine response

    PubMed Central

    Gilmartin, Allissia A.; Petri, William A.

    2015-01-01

    Environmental enteropathy (EE) is a poorly defined state of intestinal inflammation without overt diarrhoea that occurs in individuals exposed over time to poor sanitation and hygiene. It is characterized pathologically by small intestine villous blunting and inflammation. In children from low-income countries, it is implicated as a cause of malnutrition, oral vaccine failure and impaired cognitive development. Here we review the search for non-invasive biomarkers to measure EE non-invasively, and assess the current evidence linking EE to malnutrition, vaccine failure and neurocognitive development. PMID:25964455

  17. Protein Loosing Enteropathy Secondary to Strongyloidiasis: Case Report and Review of the Literature

    PubMed Central

    El Hajj, Weam; Nakad, Gilbert; Abou Rached, Antoine

    2016-01-01

    Strongyloidiasis is a helminthic disease which affects millions around the world resulting in a significant burden in certain high risk groups. It is rarely reported in the Lebanese population probably due to the low index of suspicion in common practice. We are reporting a case of strongyloidiasis that was found in an elderly patient presenting initially with dyspnea followed by skin rash, protein loosing enteropathy, diarrhea, and abdominal pain while on corticosteroid therapy. The diagnosis was suspected based on clinical presentation in addition to peripheral eosinophilia. We will also describe the upper and lower endoscopic aspects of the disease, as well as histologic findings on duodenal and colonic biopsies. PMID:26881152

  18. Early-Onset Autoimmune Disease as a Manifestation of Primary Immunodeficiency

    PubMed Central

    Carneiro-Sampaio, Magda; Coutinho, Antonio

    2015-01-01

    Autoimmune disorders (AID) have been increasingly observed in association with primary immunodeficiencies (PIDs). Here, we discuss the interface between PID and AID, focusing on autoimmune manifestations early in life, which can be diagnostic clues for underlying PIDs. Inflammatory bowel disease in infants and children has been associated with IL-10 and IL-10R deficiencies, chronic granulomatous disease, immunedysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (IPEX), autoinflammatory disorders, and others. Some PIDs have been identified as underlying defects in juvenile systemic lupus erythematosus: C1q-, IgA-, IgM deficiencies, alterations of the IFN-α pathway (in Aicardi–Goutières syndrome due to TREX1 mutation). IPEX (due to FOXP3 mutation leading to Treg cell deficiency), usually appearing in the first months of life, was recently observed in miscarried fetuses with hydrops who presented with CD3+ infiltrating lymphocytes in the pancreas. Hemophagocytic lymphohistiocytosis due to perforin deficiency was also identified as a cause of fetal hydrops. In conclusion, PID should be suspected in any infant with signs of autoimmunity after excluding transferred maternal effects, or in children with multiple and/or severe AID. PMID:25999944

  19. Diagnostic criteria of autoimmune hepatitis.

    PubMed

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

    2014-01-01

    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

  20. Prenatal immunotoxicant exposure and postnatal autoimmune disease.

    PubMed Central

    Holladay, S D

    1999-01-01

    Reports in humans and rodents indicate that immune development may be altered following perinatal exposure to immunotoxic compounds, including chemotherapeutics, corticosteroids, polycyclic hydrocarbons, and polyhalogenated hydrocarbons. Effects from such exposure may be more dramatic or persistent than following exposure during adult life. For example, prenatal exposure to the insecticide chlordane or to the polycyclic aromatic hydrocarbon benzo[(italic)a(/italic)]pyrene produces what appears to be lifelong immunosuppression in mice. Whether prenatal immunotoxicant exposure may predispose the organism to postnatal autoimmune disease remains largely unknown. In this regard, the therapeutic immunosuppressant cyclosporin A (CsA) crosses the placenta poorly. However, lethally irradiated rodents exposed to CsA postsyngeneic bone marrow transplant (i.e., during re-establishment of the immune system) develop T-cell-mediated autoimmune disease, suggesting this drug may produce a fundamental disruption in development of self-tolerance by T cells. The environmental contaminant 2,3,7, 8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD) crosses the placenta and produces fetal thymic effects (italic)in vivo(/italic) similar to effects of CsA in fetal thymic organ culture, including inhibited thymocyte maturation and reduced expression of thymic major histocompatability complex class II molecules. These observations led to the suggestion that gestational exposure to TCDD may interfere with normal development of self-tolerance. Possibly supporting this hypothesis, when mice predisposed to development of autoimmune disease were treated with TCDD during gestation, postnatal autoimmunity was exacerbated. Similar results have been reported for mice exposed to diethylstilbestrol during development. These reports suggest that prenatal exposure to certain immunotoxicants may play a role in postnatal expression of autoimmunity. PMID:10502532

  1. Transitioning from Idiopathic to Explainable Autoimmune Hepatitis.

    PubMed

    Czaja, Albert J

    2015-10-01

    Autoimmune hepatitis lacks an identifiable cause, and its diagnosis requires the exclusion of etiologically defined diseases that resemble it. Insights into its pathogenesis are moving autoimmune hepatitis from an idiopathic to explainable disease, and the goal of this review is to describe the insights that are hastening this transition. Two types of autoimmune hepatitis are justified by serological markers, but they also have distinctive genetic associations (DRB1 and DQB1 genes) and autoantigens. DRB1 alleles are the principal susceptibility factors in white adults, and a six amino acid sequence encoded in the antigen-binding groove of class II molecules of the major histocompatibility complex can influence the selection of autoantigens. Polymorphisms, including variants of SH2B3 and CARD10 genes, may affect immune reactivity and disease severity. The cytochrome mono-oxygenase, CYP2D6, is the autoantigen associated with type 2 autoimmune hepatitis, and it shares homologies with multiple viruses that might promote self-intolerance by molecular mimicry. Chemokines, especially CXCL9 and CXCL10, orchestrate the migration of effector cells to sites of injury and are associated with disease severity. Cells of the innate and adaptive immune responses promote tissue damage, and possible deficiencies in the number and function of regulatory T cells may facilitate the injurious process. Receptor-mediated apoptosis is the principal mechanism of hepatocyte loss, and cell-mediated and antibody-dependent mechanisms of cytotoxicity also contribute. Insights that explain autoimmune hepatitis will allow triggering exogenous antigens to be characterized, risk management to be improved, prognostic indices to be refined, and site-specific therapeutic interventions to emerge. PMID:25999246

  2. [Autoimmune hemolytic anemia].

    PubMed

    Karasawa, Masamitsu

    2008-03-01

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

  3. [Diagnostics of autoimmune diseases].

    PubMed

    Beleznay, Zsuzsanna; Regenass, Stephan

    2008-09-01

    Autoantibodies play a key role in diagnostic laboratories as markers of autoimmune diseases. In addition to their role as markers they mediate diverse effects in vivo. Autoantibodies with protective effect have been described. Natural protective IgM autoantibodies against tumour-antigens of malignant cells or their precursors may contribute to increased survival rates of carcinoma patients. In a mouse model of systemic lupus erythematosus it has been shown that anti-dsDNA IgM autoantibodies protect from glomerular damage. In contrast, a direct pathogenic role of autoantibodies has been well established e.g. in myasthenia gravis or in Goodpasture syndrome. Similarly autoantibodies against SSA Ro52 are detrimental in neonatal lupus erythematosus with congenital heart block. Moreover, putatively protective autoantibodies may become pathogenic during the course of the disease such as the onconeuronal autoantibodies whose pathogenicity depends on their compartmentalisation. In patients with paraneoplastic syndromes tumour cells express proteins that are also naturally present in the brain. Anti-tumour autoantibodies which temporarily suppress tumour growth can provoke an autoimmune attack on neurons once having crossed the blood-brain barrier and cause specific neurological symptoms. Only a restricted number of autoantibodies are useful follow-up markers for the effectiveness of treatment in autoimmune diseases. Certain autoantibodies hold prognostic value and appear years or even decades before the diagnosis of disease such as the antimitochondrial antibodies in primary biliary cirrhosis or anti-citrullinated protein (CCP)-antibodies in rheumatoid arthritis. It is crucial to know whether the autoantibodies in question recognise linear or conformational epitopes in order to choose the appropriate detection methods. Indirect immunofluorescence microscopy remains a very useful tool for confirmation of results of commercially available immunoassays and for detection of

  4. Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

    PubMed Central

    Wallace, John L

    2013-01-01

    This article reviews the latest developments in understanding the pathogenesis, detection and treatment of small intestinal damage and bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs). With improvements in the detection of NSAID-induced damage in the small intestine, it is now clear that this injury and the associated bleeding occurs more frequently than that occurring in the stomach and duodenum, and can also be regarded as more dangerous. However, there are no proven-effective therapies for NSAID-enteropathy, and detection remains a challenge, particularly because of the poor correlation between tissue injury and symptoms. Moreover, recent studies suggest that commonly used drugs for protecting the upper gastrointestinal tract (i.e., proton pump inhibitors) can significantly worsen NSAID-induced damage in the small intestine. The pathogenesis of NSAID-enteropathy is complex, but studies in animal models are shedding light on the key factors that contribute to ulceration and bleeding, and are providing clues to the development of effective therapies and prevention strategies. Novel NSAIDs that do not cause small intestinal damage in animal models offer hope for a solution to this serious adverse effect of one of the most widely used classes of drugs. PMID:23569332

  5. A case of colon perforation due to enteropathy-associated T-cell lymphoma

    PubMed Central

    Kim, Jun Bong; Kim, Seong Hwan; Cho, Young Kwan; Ahn, Sang Bong; Jo, Yun Ju; Park, Young Sook; Lee, Ji Hyun; Kim, Dong Hee; Lee, Hojung; Jung, Yun Young

    2013-01-01

    Enteropathy-associated T-cell lymphoma (EATL) is an extremely rare disease, which is often related to gluten-sensitive enteropathy. It is an uncommon intestinal lymphoma with very poor prognosis and high mortality rate. In the absence of specific symptoms or radiological findings, it is difficult to diagnose early. Major complications of EATL have been known as intestinal perforation or obstruction, and only 5 cases of EATL are reported in South Korea. In this study, we report a case of 71-year-old male with symptoms of diarrhea, which later it progressed into cancer perforation of the colon. The initial colonoscopic findings were normal and computed tomography scan demonstrated a segmental wall thickening of the distal ascending colon with nonspecific multiple small lymphnodes, along the ileocolic vessels, but no signs of mass or obstruction. The histologic findings of resected specimen confirmed EATL type II. Patient expired two weeks after the operation. Therefore, we emphasize the need of random biopsy in the presence of normal mucosa appearance on colonoscopy for the early diagnosis of EATL. PMID:23555174

  6. Cytokines and autoimmunity.

    PubMed Central

    Cavallo, M G; Pozzilli, P; Thorpe, R

    1994-01-01

    Although the immunopathology of most autoimmune diseases has been well defined, the mechanisms responsible for the breakdown of self-tolerance and which lead to the development of systemic and organ-specific autoaggression are still unclear. Evidence has accumulated which supports a role for a disregulated production of cytokines by leucocytes and possibly other cells in the pathogenesis of some autoimmune diseases. However, due to the complexity and heterogeneity of cytokine effects in the regulation of the immune response, it is difficult to determine whether abnormalities in the patterns of cytokine production are primary or secondary to the pathological process. Confusion is also caused by the fact that the biological activities of cytokines are multiple and often overlapping, and consequently it is difficult to focus on a unique effect of any one cytokine. Characterization of the potential and actual involvement of cytokines is important not only for a better understanding of the pathogenesis of autoimmune conditions, but particularly because of the implications for the development of immunotherapeutic strategies for the prevention and treatment of the diseases. PMID:8149655

  7. Autoimmune mechanisms in psoriasis.

    PubMed

    Reeves, W H

    1991-09-01

    Psoriasis is a chronic papulosquamous skin disorder affecting 1% to 3% of the general population. There is increasing evidence that immunologic mechanisms are involved in the pathogenesis of psoriasis, and that a link between psoriasis and autoimmunity may exist. A variety of autoantibodies has been observed in psoriasis including antinuclear antibodies, antibodies to small nuclear and cytoplasmic ribonucleoproteins, and antibodies to epidermal cells. UV light treatment of psoriasis may play a role in inducing these autoantibodies in some individuals. Recent evidence that activated T cells in psoriatic plaques may produce interferon-gamma leading to the appearance of ectopic class II major histocompatibility products on the surface of keratinocytes also supports the idea of a link between psoriasis and disordered immunoregulation. The immunologic abnormalities in psoriasis and the association of psoriasis with particular types of autoantibodies raise the possibility that a common etiology may underlie both psoriasis and autoimmunity in some patients, but the different responses of the two diseases to UV light treatment and certain pharmacological agents suggest that psoriasis may not have an autoimmune pathogenesis. PMID:1931571

  8. Autoantibodies in Autoimmune Pancreatitis

    PubMed Central

    Smyk, Daniel S.; Rigopoulou, Eirini I.; Koutsoumpas, Andreas L.; Kriese, Stephen; Burroughs, Andrew K.; Bogdanos, Dimitrios P.

    2012-01-01

    Autoimmune pancreatitis (AIP) was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA) positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis. PMID:22844291

  9. The spectrum of autoimmune encephalopathies.

    PubMed

    Dubey, Divyanshu; Sawhney, Anshudha; Greenberg, Benjamin; Lowden, Andrea; Warnack, Worthy; Khemani, Pravin; Stuve, Olaf; Vernino, Steven

    2015-10-15

    Despite being a potentially reversible neurological condition, no clear guidelines for diagnosis or management of autoimmune encephalitis exist. In this study we analyzed clinical presentation, laboratory and imaging characteristics, and outcome of autoimmune encephalitis from three teaching hospitals. Non-paraneoplastic autoimmune encephalitis associated with antibodies against membrane antigens was the most common syndrome, especially in the pediatric population. Clinical outcome was better for patients with shorter latency from symptom onset to diagnosis and initiation of immunomodulation. Patients with underlying malignancy were less likely to respond well to immunomodulatory therapy. The clinical spectrum of autoimmune encephalitis is fairly broad, but prompt recognition and treatment often leads to excellent outcome. PMID:26439968

  10. [Autoimmune Associated Encephalitis and Dementia].

    PubMed

    Watanabe, Osamu

    2016-04-01

    Antibodies against various neural surface antigens induce cognitive impairments. Anti-VGKC (voltage gated potassium channel) complex antibodies are well known as one of the causative autoantibodies. An anti-VGKC antibody was identified as the autoantibody in acquired neuromyotonia (Isaacs' syndrome), which causes muscle cramps and difficulty in opening the palm of the hands. However, this antibody also tests positive in autoimmune limbic encephalitis, which has a subacute progress and causes poor memory or epilepsy attacks. Typical cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures. In recent years, the true target antigens of the anti-VGKC antibody of this VGKC limbic encephalitis have been recognized as leucine rich glioma inactivated protein (LGI)-1 and others. These antibodies to amnesia-related LGI-1 in limbic encephalitis neutralize the LGI-1-ADAM22 (an anchor protein) interaction and reduce synaptic AMPA receptors. There have been reports of limbic encephalitis associated with anti-VGKC complex antibodies mimicking Creutzfeldt-Jakob disease (CJD). Less than 2% of the patients with sporadic CJD (sCJD) develop serum anti-VGKC complex antibodies and, when positive, only at low titres. Low titres of these antibodies occur only rarely in suspected patients with sCJD, and when present, should be interpreted with caution. PMID:27056852

  11. Autoimmune diseases and myelodysplastic syndromes.

    PubMed

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

    2016-05-01

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

  12. Autoimmune muscle disease.

    PubMed

    Mammen, Andrew

    2016-01-01

    Patients with polymyositis (PM), dermatomyositis (DM), and immune-mediated necrotizing myopathy (IMNM) present with the subacute onset of symmetric proximal muscle weakness, elevated muscle enzymes, myopathic findings on electromyography, and autoantibodies. DM patients are distinguished by their cutaneous manifestations. Characteristic features on muscle biopsy include the invasion of nonnecrotic muscle fibers by T cells in PM, perifascicular atrophy in DM, and myofiber necrosis without prominent inflammation in IMNM. Importantly, these are regarded as autoimmune diseases and most patients respond partially, if not completely, to immunosuppressive therapy. Patients with inclusion body myositis (IBM) usually present with the insidious onset of asymmetric weakness in distal muscles (e.g., wrist flexors, and distal finger flexors), often when more proximal muscle groups are relatively preserved. Although IBM muscle biopsies usually have focal invasion of myofibers by lymphocytes, the majority of IBM biopsies also include rimmed vacuoles. While most IBM patients do have autoantibodies, treatment with immunosuppressive agents does not improve their clinical course. Along with the presence of abnormally aggregated proteins on muscle biopsy, the refractory nature and relentless course of IBM suggest that the underlying pathophysiology may include a dominant myodegenerative component. This chapter will focus on the epidemiology, clinical presentation, and treatment of the autoimmune myopathies and IBM. An emphasis will be placed on recent advances, indicating that these are a diverse family of diseases and that each of more than a dozen myositis autoantibodies is associated with a distinct clinical phenotype. PMID:27112692

  13. [Autoimmune lymphoproliferative syndrome].

    PubMed

    Rodrigues, Vera; Conde, Marta; Figueiredo, António; Vasconcelos, Júlia; Dias, Alexandra

    2011-01-01

    The Autoimmune Lymphoproliferative Syndrome (ALPS) is an impairment of lymphocyte apoptosis expressed by generalized non-malignant lymphoproliferation, lymphadenopathy and/or splenomegaly. This article describes a seven and 14 year old males. The first one was admitted at 3 years of age with fever, bicytopenia and generalized lymphadenopathy. Hystopathological analysis of lymph nodes showed reactive follicular hyperplasia and marked paracortical expansion. He was readmitted three years later presenting herpes zoster and similar clinical features. High levels of IL-10 and increasing tendency of Fas-L in plasma and serum. The second child was admitted at 13 years of age presenting thigh and gluteus cellulitis, anemia and neutropenia. T lymphocytes aß+CD4-CD8- 3,1%. Hystopathological analysis of lymph nodes showed marked paracortical hyperplasia. Both children are treated with mycophenolate mofetil with good response. ALPS is an underestimated entity that must be considered in non malign lymphoproliferation, autoimmunity and expansion of an unusual population of a/ßCD3+CD4-CD8-(double-negative T cells>1%). PMID:22525637

  14. [Hydroxychloroquine for autoimmune diseases].

    PubMed

    Danza, Álvaro; Graña, Diego; Goñi, Mabel; Vargas, Andrea; Ruiz-Irastorza, Guillermo

    2016-02-01

    Hydroxychloroquine (HCQ) is by far the most frequently used antimalarial for the management of Systemic Autoimmune Diseases. It has immunomodulatory, hypolipidemic, hypoglycemic and antithrombotic properties and it diminishes the risk of malignancies. The most important mechanisms to explain the immunomodulatory actions are its ability to reduce inflammatory pathways and Toll-like receptors activation. The safety profile is favorable. In spite of its low frequency, retinal toxicity is potentially severe. In systemic lupus erythematous HCQ therapy reduces activity, the accrual of organ damage, risk of infections and thrombosis and improves the cardiometabolic profile. It contributes to induce lupus nephritis remission, spares steroid use and increases survival rates. In rheumatoid arthritis, it improves cardiometabolic risk and has a favorable effect in joint inflammation. In Sjögren's syndrome, an increased lacrimal quality as well as an improvement in objective and subjective inflammatory markers has been demonstrated with HCQ. In Antiphospholipid Syndrome, HCQ is effective in primary and secondary thrombosis prevention. The effectiveness of the drug in other systemic autoimmune diseases is less established. HCQ therapy may improve dermatological manifestations in Dermatomyositis and may have a positive effects in the treatment of Sarcoidosis and Still disease. PMID:27092678

  15. Aquaporin-4 autoimmunity

    PubMed Central

    Zekeridou, Anastasia

    2015-01-01

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

  16. Infections and autoimmune diseases.

    PubMed

    Bach, Jean-François

    2005-01-01

    The high percentage of disease-discordant pairs of monozygotic twins demonstrates the central role of environmental factors in the etiology of autoimmune diseases. Efforts were first focussed on the search for triggering factors. The study of animal models has clearly shown that infections may trigger autoimmune diseases, as in the case of Coxsackie B4 virus in type I diabetes and the encephalomyocarditis virus in autoimmune myositis, two models in which viruses are thought to act by increasing immunogenicity of autoantigens secondary to local inflammation. The induction of a Guillain-Barré syndrome in rabbits after immunization with a peptide derived from Campylobacter jejuni is explained by mimicry between C. jejuni antigens and peripheral nerve axonal antigens. Other models involve chemical modification of autoantigens, as in the case of iodine-induced autoimmune thyroiditis. These mechanisms have so far only limited clinical counterparts (rheumatic fever, Guillain-Barré syndrome and drug-induced lupus or myasthenia gravis) but one may assume that unknown viruses may be at the origin of a number of chronic autoimmune diseases, such as type I diabetes and multiple sclerosis) as illustrated by the convergent data incriminating IFN-alpha in the pathophysiology of type I diabetes and systemic lupus erythematosus. Perhaps the difficulties met in identifying the etiologic viruses are due to the long lag time between the initial causal infection and onset of clinical disease. More surprisingly, infections may also protect from autoimmune diseases. Western countries are being confronted with a disturbing increase in the incidence of most immune disorders, including autoimmune and allergic diseases, inflammatory bowel diseases, and some lymphocyte malignancies. Converging epidemiological evidence indicates that this increase is linked to improvement of the socio-economic level of these countries, posing the question of the causal relationship and more precisely the

  17. Disseminated mycobacterium avium complex as protein-losing enteropathy in a non-HIV patient.

    PubMed

    Konjeti, Venkata Rajesh; Paluri, Sravanthi

    2014-01-01

    Disseminated mycobacterium avium complex (MAC) causing protein-losing enteropathy (PLE) due to intestinal lymphangiectasia (IL) in a non-HIV immunocompromised state is extremely rare. We present a case of 56-year-old male who was evaluated for worsening dyspnea and found to have right-sided chylous pleural effusion as well as worsening abdominal and retroperitoneal lymphadenopathy. He had a history of psoriasis for which hewas on etanercept and alefacept which were stopped two years prior to the presentation. The evaluation revealed a MAC infection in his lymph nodes--a low CD4 count but negative for HIV. He was started on MAC therapy. He subsequently developed noninfectious diarrhea, Hypoalbuminemia, recurrentpleural effusions, ascites, and Pneumocystis jiroveci pneumonia (PJP). Despite appropriate antibiotics and management--including total parental nutrition (TPN) with a medium-chain triglyceride enriched low fat diet--the patient's clinical condition deteriorated rapidly resulting in death. PMID:25672059

  18. Ulcerating and stenosing enteropathy treated with misoprostol: a case report with analysis of prostaglandin metabolism.

    PubMed

    Havelund, Troels; Jensen, Boye L; Vinholt, Pernille J; Engvad, Birte; Stubbe, Jane

    2012-10-01

    A case of a 40-year-old man with chronic anaemia because of nonspecific ulcerating and stenosing enteropathy is presented. The diagnosis was made on the basis of capsule endoscopy, histology of resected ileum and no use of NSAIDs. He showed a clinical response to treatment with misoprostol, and therefore, he was investigated for a possible impairment in eicosanoid biosynthesis compared with healthy controls. No deficient synthesis of prostacyclin, prostaglandin E2 and thromboxane was found on examination of metabolites in blood and urine. This suggests a normal release of arachidonic acid from phospholipids. Ex-vivo cyclooxygenase (COX) assays showed normal COX-1 and COX-2 activities. The clinical response to treatment with the prostaglandin E1 analogue misoprostol suggests a defective prostaglandin E synthesis in the intestinal mucosa. PMID:22786573

  19. Enteropathy Associated T Cell Lymphoma – A Case Report of An Uncommon Extranodal T Cell Lymphoma

    PubMed Central

    V, Geetha; Kudva, Ranjini

    2014-01-01

    Enteropathy associated T cell lymphoma is a rare primary intestinal lymphoma. It is often, but not always associated with celiac disease. Intraepithelial T cells are postulated as the cell of origin. It is a rare disease accounting for fewer than 5% of all gastrointestinal tract lymphomas. Recent studies indicate that EATL consists of two diseases that are morphologically and genetically distinct and differ with respect to their frequency of association with celiac disease. Current WHO classification recognises two subtypes of EATL – type 1 (classic) and type 2, based on morphology and immunophenotype. EATL type 1 is a large cell lymphoma which is more common and is more commonly associated with celiac disease compared to type 2. Most common site of involvement is the small intestine. We report a case of EATL type 1, in a 62-year-old female patient who presented with features of intestinal obstruction. However, she did not have spruce like featutes. PMID:25478355

  20. Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model

    PubMed Central

    Brown, Eric M.; Wlodarska, Marta; Willing, Benjamin P.; Vonaesch, Pascale; Han, Jun; Reynolds, Lisa A.; Arrieta, Marie-Claire; Uhrig, Marco; Scholz, Roland; Partida, Oswaldo; Borchers, Christoph H.; Sansonetti, Philippe J.; Finlay, B. Brett

    2015-01-01

    Environmental enteropathy (EE) is a subclinical chronic inflammatory disease of the small intestine and has a profound impact on the persistence of childhood malnutrition worldwide. However, the aetiology of the disease remains unknown and no animal model exists to date, the creation of which would aid in understanding this complex disease. Here we demonstrate that early-life consumption of a moderately malnourished diet, in combination with iterative oral exposure to commensal Bacteroidales species and Escherichia coli, remodels the murine small intestine to resemble features of EE observed in humans. We further report the profound changes that malnutrition imparts on the small intestinal microbiota, metabolite and intraepithelial lymphocyte composition, along with the susceptibility to enteric infection. Our findings provide evidence indicating that both diet and microbes combine to contribute to the aetiology of EE, and describe a novel murine model that can be used to elucidate the mechanisms behind this understudied disease. PMID:26241678

  1. Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model.

    PubMed

    Brown, Eric M; Wlodarska, Marta; Willing, Benjamin P; Vonaesch, Pascale; Han, Jun; Reynolds, Lisa A; Arrieta, Marie-Claire; Uhrig, Marco; Scholz, Roland; Partida, Oswaldo; Borchers, Christoph H; Sansonetti, Philippe J; Finlay, B Brett

    2015-01-01

    Environmental enteropathy (EE) is a subclinical chronic inflammatory disease of the small intestine and has a profound impact on the persistence of childhood malnutrition worldwide. However, the aetiology of the disease remains unknown and no animal model exists to date, the creation of which would aid in understanding this complex disease. Here we demonstrate that early-life consumption of a moderately malnourished diet, in combination with iterative oral exposure to commensal Bacteroidales species and Escherichia coli, remodels the murine small intestine to resemble features of EE observed in humans. We further report the profound changes that malnutrition imparts on the small intestinal microbiota, metabolite and intraepithelial lymphocyte composition, along with the susceptibility to enteric infection. Our findings provide evidence indicating that both diet and microbes combine to contribute to the aetiology of EE, and describe a novel murine model that can be used to elucidate the mechanisms behind this understudied disease. PMID:26241678

  2. [Acute intestinal obstruction revealing enteropathy associated t-cell lymphoma, about a case].

    PubMed

    Garba, Abdoul Aziz; Adamou, Harissou; Magagi, Ibrahim Amadou; Brah, Souleymane; Habou, Oumarou

    2016-01-01

    Enteropathy associated T-cell lymphoma (EATL) is a rare complication of celiac disease (CD). We report a case of EATL associated with CD revealed by acute intestinal obstruction. A North African woman of 38 years old with a history of infertility and chronic abdominal pain was admitted in emergency with acute intestinal obstruction. During the surgery, we found a tumor on the small intestine with mesenteric lymphadenopathy. Histology and immunohistochemistry of the specimen objectified a digestive T lymphoma CD3+ and immunological assessment of celiac disease was positive. The diagnosis of EATL was thus retained. Chemotherapy (CHOEP protocol) was established as well as gluten-free diet with a complete response to treatment. The EATL is a rare complication of CD that can be revealed by intestinal obstruction. The prognosis can be improved by early treatment involving surgery and chemotherapy. Its prevention requires early diagnosis of celiac and gluten-free diets. PMID:27217874

  3. Prevalence of porcine proliferative enteropathy and its control with tylosin in Korea.

    PubMed

    Lee, S W; Kim, T J; Park, S Y; Song, C S; Chang, H K; Yeh, J K; Park, H I; Lee, J B

    2001-12-01

    Porcine proliferative enteropathy(PPE) is an enteric disease been caused by Lawsonia intracellularis. It has become one of the critical problems in the pig industry. To investigate the prevalence of PPE in Korea, serum samples of 828 pigs from 65 herds were tested using indirect immunofluorescence antibody technique(IFA). The infection rate in individual pigs varied from 44 to 69%, whereas 100% in pig farms. The infection frequency was 57, 44.9, and 59.4% according to age respectively. Administration of tylosin in feed at a concentration of 110 ppm for 14 days reduced the infection rate of the farms. These data indicated that the high prevalence of PPE may be controlled by tylosin. PMID:12441690

  4. Environmental Triggers of Autoimmune Thyroiditis

    PubMed Central

    Burek, C. Lynne; Talor, Monica V.

    2009-01-01

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

  5. Environmental triggers of autoimmune thyroiditis.

    PubMed

    Burek, C Lynne; Talor, Monica V

    2009-01-01

    Autoimmune thyroiditis is among the most prevalent of all the autoimmunities. Autoimmune thyroiditis is multifactorial with contributions from genetic and environmental factors. Much information has been published about the genetic predisposition to autoimmune thyroiditis both in experimental animals and humans. There is, in contrast, very little data on environmental agents that can serve as the trigger for 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.H2(h4) mouse to explore the influence of iodine and other environmental factors on autoimmune thyroiditis. PMID:19818584

  6. Mast Cell and Autoimmune Diseases

    PubMed Central

    Xu, Yunzhi; Chen, Guangjie

    2015-01-01

    Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases. PMID:25944979

  7. Inflammation and epithelial cell injury in AIDS enteropathy: involvement of endoplasmic reticulum stress

    PubMed Central

    Maingat, Ferdinand; Halloran, Brendan; Acharjee, Shaona; van Marle, Guido; Church, Deirdre; Gill, M. John; Uwiera, Richard R. E.; Cohen, Eric A.; Meddings, Jon; Madsen, Karen; Power, Christopher

    2011-01-01

    Immunosuppressive lentivirus infections, including human, simian, and feline immunodeficiency viruses (HIV, SIV, and FIV, respectively), cause the acquired immunodeficiency syndrome (AIDS), frequently associated with AIDS enteropathy. Herein, we investigated the extent to which lentivirus infections affected mucosal integrity and intestinal permeability in conjunction with immune responses and activation of endoplasmic reticulum (ER) stress pathways. Duodenal biopsies from individuals with HIV/AIDS exhibited induction of IL-1β, CD3ε, HLA-DRA, spliced XBP-1(Xbp-1s), and CHOP expression compared to uninfected persons (P<0.05). Gut epithelial cells exposed to HIV-1 Vpr demonstrated elevated TNF-α, IL-1β, spliced Xbp-1s, and CHOP expression (P<0.05) together with calcium activation and disruption of epithelial cell monolayer permeability. In addition to reduced blood CD4+ T lymphocyte levels, viral loads in the gut and plasma were high in FIV-infected animals (P<0.05). FIV-infected animals also exhibited a failure to gain weight and increased lactulose/mannitol ratios compared with uninfected animals (P<0.05). Proinflammatory and ER stress gene expression were activated in the ileum of FIV-infected animals (P<0.05), accompanied by intestinal epithelial damage with loss of epithelial cells and leukocyte infiltration of the lamina propria. Lentivirus infections cause gut inflammation and ensuing damage to intestinal epithelial cells, likely through induction of ER stress pathways, resulting in disruption of gut functional integrity.—Maingat, F., Halloran, B., Acharjee, S., van Marle, G., Church, D., Gill, M. J., Uwiera, R. R. E., Cohen, E. A., Meddings, J., Madsen, K., Power, C. Inflammation and epithelial cell injury in AIDS enteropathy: involvement of endoplasmic reticulum stress. PMID:21427211

  8. Serologic follow-up of a repopulated swine herd after an outbreak of proliferative hemorrhagic enteropathy

    PubMed Central

    Guedes, Roberto M.C.; Gebhart, Connie J.; Armbruster, Greg A.; Roggow, Brian D.

    2002-01-01

    Lawsonia intracellularis is an obligate intracellular organism that causes porcine proliferative enteropathy, a widespread infectious disease. Very little is known about the immune response and the epidemiologic features of the disease in the field. The aims of this study were to evaluate the duration and titers of antibody specific for L. intracellularis in gilts after an outbreak of proliferative hemorrhagic enteropathy (PHE), to evaluate maternal antibodies in piglets, and to evaluate seroconversion and fecal shedding in growing–finishing pigs. Thirty-six gilts in a herd that had recently experienced an outbreak of PHE, including 13 that had recovered, were bled 3 wk after the beginning of the outbreak and then every 3 wk until they became seronegative in 2 consecutive tests. Fourteen piglets from 5 gilts seropositive at farrowing and 5 piglets from 2 sows that remained seronegative were bled once or twice at the farrowing house and then every 3 wk until they reached market age. Fecal samples from these pigs were tested by polymerase chain reaction at 7 wk of age and then on the days of blood collection. After the PHE outbreak, the gilts had high serum antibody levels; the levels decreased over time, but antibody was still detectable for up to 3 mo in some animals. Four piglets from sows that were seropositive at farrowing had detectable passive antibodies up to 5 wk of age. Some nursery pigs started shedding L. intracellularis around 7 wk of age; peak shedding was observed between 13 and 16 wk. Antibody was not detected until 16 wk of age and was more often detected between 19 and 22 wk. PMID:12418781

  9. Identification of EpCAM as the Gene for Congenital Tufting Enteropathy

    PubMed Central

    Sivagnanam, Mamata; Mueller, James L.; Lee, Hane; Chen, Zugen; Nelson, Stanley F.; Turner, Dan; Zlotkin, Stanley H.; Pencharz, Paul B.; Ngan, Bo-Yee; Libiger, Ondrej; Schork, Nicholas J.; Lavine, Joel E.; Taylor, Sharon; Newbury, Robert O.; Kolodner, Richard D.; Hoffman, Hal M.

    2008-01-01

    Background and Aims Congenital Tufting Enteropathy (CTE) is a rare autosomal recessive diarrheal disorder presenting in the neonatal period. CTE is characterized by intestinal epithelial cell dysplasia leading to severe malabsorption and significant morbidity and mortality. The pathogenesis and genetics of this disorder are not well understood. The objective of this study was to identify the gene responsible for CTE. Methods A family with 2 children affected with CTE was identified. The affected children are double second cousins providing significant statistical power for linkage. Using Affymetrix 50K Single Nucleotide Polymorphism (SNP) chips, genotyping was performed on only two patients and one unaffected sibling. Direct DNA sequencing of candidate genes, RT-PCR, immunohistochemistry, and Western blotting were performed on specimens from patients and controls. Results SNP homozygosity mapping identified a unique 6.5 MB haplotype of homozygous SNPs on chromosome 2p21 where approximately 40 genes are located. Direct sequencing of genes in this region revealed homozygous G > A substitution at the donor splice site of exon 4 in Epithelial Cell Adhesion Molecule (EpCAM) of affected patients. RT-PCR of duodenal tissue demonstrated a novel alternative splice form with deletion of exon 4 in affected patients. Immuno-histochemistry and Western blot of patient intestinal tissue revealed decreased expression of EpCAM. Direct sequencing of EpCAM from two additional unrelated patients revealed novel mutations in the gene. Conclusions Mutations in the gene for EpCAM are responsible for Congenital Tufting Enteropathy. This information will be used to gain further insight into the molecular mechanisms of this disease. PMID:18572020

  10. Cannabidiol Limits T Cell–Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

    PubMed Central

    Lee, Wen-Shin; Erdelyi, Katalin; Matyas, Csaba; Mukhopadhyay, Partha; Varga, Zoltan V; Liaudet, Lucas; Hask’, György; ’iháková, Daniela; Mechoulam, Raphael; Pacher, Pal

    2016-01-01

    Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a nonpsychoactive constituent of marijuana that exerts antiinflammatory effects independent of classical cannabinoid receptors. Recently, 80 clinical trials have investigated the effects of CBD in various diseases from inflammatory bowel disease to graft versus host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received U.S. Food and Drug Administration approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell–mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T-cell infiltration, profound inflammatory response and fibrosis (measured by quantitative real-time polymerase chain reaction, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with a pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ T cell–mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. In conclusion, CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation. PMID:26772776

  11. Autoimmunity in neuromuscular disease.

    PubMed

    Newsom-Davis, J

    1988-01-01

    A number of confounding factors can be identified from the search for autoimmune mechanisms over the last 2 decades that may be relevant for future studies. (1) An apparently homogeneous clinical disorder may represent more than one disease process and thereby imply antibody/antigen heterogeneity as, for example, in MG with and without detectable anti-AChR antibodies. In some cases, physiologic studies allow the different forms of the disease to be distinguished as in AIDP and acute inflammatory axonal polyneuropathy. (2) A homogeneous disorder (e.g., LEMS) may have at least two different triggering mechanisms (SCLC and an unknown stimulus). (3) Antigen density may be too low to be detected by the immunohistologic techniques available, as initially occurred in MG and LEMS. (4) Autoantibodies may be detected that are irrelevant to the primary disease, such as anti-striated muscle antibodies in MG. (5) Poor antibody cross-reactivity between species may mean that the pathogenic antibody is undetected in binding assays or in experimental passive transfer studies. For example, anti-AChR antibody in MG shows less than 5% reactivity with Torpedo AChR. (6) A poor regenerative capacity of the target antigen may mean that reduction of circulating autoantibodies by either plasma exchange or ISD treatment is not associated with detectable clinical improvement, as may be the case in SSN in which DRG cells appear to be the target. TABLE 5 summarizes the extent to which the data reviewed have established a role for pathogenic antibodies in the light of the postulates for autoimmunity set out earlier and ranks the disorders accordingly. Only in MG with detectable anti-AChR antibody are all the postulates met, including definition of the antigen, experimental passive transfer by the IgG fraction of MG sera, active immunization of experimental animals, and propagation. In both LEMS and the IgM kappa anti-MAG demyelinating neuropathy the antigen is known, although better

  12. Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3.

    PubMed

    Haapaniemi, Emma M; Kaustio, Meri; Rajala, Hanna L M; van Adrichem, Arjan J; Kainulainen, Leena; Glumoff, Virpi; Doffinger, Rainer; Kuusanmäki, Heikki; Heiskanen-Kosma, Tarja; Trotta, Luca; Chiang, Samuel; Kulmala, Petri; Eldfors, Samuli; Katainen, Riku; Siitonen, Sanna; Karjalainen-Lindsberg, Marja-Liisa; Kovanen, Panu E; Otonkoski, Timo; Porkka, Kimmo; Heiskanen, Kaarina; Hänninen, Arno; Bryceson, Yenan T; Uusitalo-Seppälä, Raija; Saarela, Janna; Seppänen, Mikko; Mustjoki, Satu; Kere, Juha

    2015-01-22

    The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of immunodysregulation polyendocrinopathy enteropathy X-linked-like syndrome. Here, we immunologically characterized 3 patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T, and p.K658N, respectively). The patients displayed multiorgan autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B-cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4(-)CD8(-)) T cells, and decreased natural killer, T helper 17, and regulatory T-cell numbers. Notably, the patient harboring the K392R mutation developed T-cell large granular lymphocytic leukemia at age 14 years. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity. PMID:25349174

  13. Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3

    PubMed Central

    Haapaniemi, Emma M.; Kaustio, Meri; Rajala, Hanna L. M.; van Adrichem, Arjan J.; Kainulainen, Leena; Glumoff, Virpi; Doffinger, Rainer; Kuusanmäki, Heikki; Heiskanen-Kosma, Tarja; Trotta, Luca; Chiang, Samuel; Kulmala, Petri; Eldfors, Samuli; Katainen, Riku; Siitonen, Sanna; Karjalainen-Lindsberg, Marja-Liisa; Kovanen, Panu E.; Otonkoski, Timo; Porkka, Kimmo; Heiskanen, Kaarina; Hänninen, Arno; Bryceson, Yenan T.; Uusitalo-Seppälä, Raija; Saarela, Janna; Seppänen, Mikko; Kere, Juha

    2015-01-01

    The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of immunodysregulation polyendocrinopathy enteropathy X-linked–like syndrome. Here, we immunologically characterized 3 patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T, and p.K658N, respectively). The patients displayed multiorgan autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B-cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4−CD8−) T cells, and decreased natural killer, T helper 17, and regulatory T-cell numbers. Notably, the patient harboring the K392R mutation developed T-cell large granular lymphocytic leukemia at age 14 years. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity. PMID:25349174

  14. Autoimmune hemolytic anemia.

    PubMed

    Dacie, J V

    1975-10-01

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

  15. Type 1 diabetes associated autoimmunity.

    PubMed

    Kahaly, George J; Hansen, Martin P

    2016-07-01

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

  16. Oral disodium cromoglycate and ketotifen for a patient with eosinophilic gastroenteritis, food allergy and protein-losing enteropathy.

    PubMed

    Suzuki, Junzo; Kawasaki, Yukihiko; Nozawa, Ruriko; Isome, Masato; Suzuki, Shigeo; Takahashi, Ai; Suzuki, Hitoshi

    2003-09-01

    We present a case report of a 10 years old boy with protein-losing enteropathy and eosinophilic gastroenteritis who had positive histamine release tests, increased allergen-specific IgE antibodies to some food items, and low levels of total serum protein and albumin. Upper gastrointestinal endoscopy revealed a number of polyps and diffuse gastritis. Biopsy specimens of the stomach and duodenum showed widespread eosinophilia and neutrophilia. Although a restricted diet was recommended, a diet which excluded foods with positive results to both histamine release test and allergen-specific IgE antibodies was poorly tolerated, and the patient rejected systemic administration of corticosteroids. Thus, we initiated an oral disodium cromoglycate (DSCG) and ketotifen therapy. After oral DSCG and ketotifen administration, the patient's condition improved gradually. Therefore, oral DSCG and ketotifen therapy might be considered as treatment option in patients with eosinophilic gastroenteritis and protein-losing enteropathy caused by food allergy. PMID:15032404

  17. Autoimmunity and inflammation in status epilepticus: from concepts to therapies.

    PubMed

    Holzer, Franz Josef; Seeck, Margitta; Korff, Christian M

    2014-10-01

    The understanding of immunological mechanisms underlying some forms of epilepsy and encephalitis has rapidly increased for the last 10 years leading to the concept of status epilepticus of autoimmune origin. Actual treatment recommendations regarding autoimmune status epilepticus are based on retrospective case studies, pathophysiological considerations and experts' opinion. In addition, there are no clear indicators to predict outcome. In situations where autoimmune mechanisms are suspected in patients with status epilepticus, there is evidence that earlier treatment is related to better outcome. Increased awareness is mandatory to decrease the number of patients with major neurological problems or fatal outcome, which is overall about 50%. We here summarize findings of all pediatric and adult patients reported to date, and review the current state of knowledge in the field of immune therapeutic approaches of status epilepticus. PMID:25201402

  18. Questions and Answers on Autoimmunity and Autoimmune Diseases

    MedlinePlus

    ... for Updates Join Our Email List For Email Marketing you can trust. Contact AARDA National Office 22100 ... Grassroots Fundraising Workplace Giving Special Events AARDA on Facebook Copyright © 2004 - 2016. American Autoimmune Related Diseases Association, ...

  19. Sensory Neuronopathy and Autoimmune Diseases

    PubMed Central

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

    2012-01-01

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

  20. Autoimmune Thyroid Diseases in Children

    PubMed Central

    Cappa, Marco; Bizzarri, Carla; Crea, Francesca

    2011-01-01

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

  1. A Randomized, Double-Blind, Placebo-Controlled Trial of Rifaximin, a Nonabsorbable Antibiotic, in the Treatment of Tropical Enteropathy

    PubMed Central

    Trehan, Indi; Shulman, Robert J.; Ou, Ching-Nan; Maleta, Kenneth; Manary, Mark J.

    2009-01-01

    OBJECTIVES Tropical enteropathy is characterized by an increased urinary lactulose-to-mannitol (L:M) ratio on a site-specific sugar absorption test and is associated with increased intestinal permeability and decreased nutrient absorptive capacity. The etiology of tropical enteropathy is postulated to be intestinal bacterial overgrowth. This study tested the hypothesis that treatment with a nonabsorbable, broad-spectrum antibiotic, rifaximin, reduces the L:M ratio in rural Malawian children, among whom tropical enteropathy is common. METHODS All children aged 3–5 years from one village were enrolled in a randomized, double-blind, placebo-controlled trial of treatment with rifaximin for 7 days. The L:M ratio was measured before and after treatment, and the change in the L:M ratio was the primary outcome. Secondary outcomes were changes in the urinary sucrose-to-lactulose (SUC:L) and sucralose-to-lactulose (SCL:L) ratios, as well as changes in the fractions of each test sugar recovered in the urine. RESULTS A total of 144 children participated in this study, of whom 76% had an elevated L:M ratio on enrollment (L:M≥0.10). Children who received rifaximin did not show an improvement in their L:M ratio compared with those who received placebo (−0.01±0.12 vs. 0.02±0.16, respectively, P = 0.51, mean±s.d.), nor were there significant differences between the two groups in excretion of lactulose, mannitol, sucralose, or sucrose, or in the SUC:L and SCL:L ratios. CONCLUSIONS Rifaximin had no effect on the tropical enteropathy of 3–5-year-old Malawian children, suggesting that small-bowel bacterial overgrowth is not an important etiological factor in this condition. PMID:19491826

  2. A Hereditary Enteropathy Caused by Mutations in the SLCO2A1 Gene, Encoding a Prostaglandin Transporter

    PubMed Central

    Esaki, Motohiro; Hirano, Atsushi; Kubokura, Naoya; Asano, Kouichi; Kochi, Shuji; Yanai, Shunichi; Fuyuno, Yuta; Shimamura, Katsuyoshi; Hosoe, Naoki; Ogata, Haruhiko; Watanabe, Takashi; Aoyagi, Kunihiko; Ooi, Hidehisa; Watanabe, Kenji; Yasukawa, Shigeyoshi; Hirai, Fumihito; Matsui, Toshiyuki; Iida, Mitsuo; Yao, Tsuneyoshi; Hibi, Toshifumi; Kosaki, Kenjiro; Kanai, Takanori; Kitazono, Takanari; Matsumoto, Takayuki

    2015-01-01

    Previously, we proposed a rare autosomal recessive inherited enteropathy characterized by persistent blood and protein loss from the small intestine as chronic nonspecific multiple ulcers of the small intestine (CNSU). By whole-exome sequencing in five Japanese patients with CNSU and one unaffected individual, we found four candidate mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. The pathogenicity of the mutations was supported by segregation analysis and genotyping data in controls. By Sanger sequencing of the coding regions, 11 of 12 other CNSU patients and 2 of 603 patients with a diagnosis of Crohn’s disease were found to have homozygous or compound heterozygous SLCO2A1 mutations. In total, we identified recessive SLCO2A1 mutations located at seven sites. Using RT-PCR, we demonstrated that the identified splice-site mutations altered the RNA splicing, and introduced a premature stop codon. Tracer prostaglandin E2 uptake analysis showed that the mutant SLCO2A1 protein for each mutation exhibited impaired prostaglandin transport. Immunohistochemistry and immunofluorescence analyses revealed that SLCO2A1 protein was expressed on the cellular membrane of vascular endothelial cells in the small intestinal mucosa in control subjects, but was not detected in affected individuals. These findings indicate that loss-of-function mutations in the SLCO2A1 gene encoding a prostaglandin transporter cause the hereditary enteropathy CNSU. We suggest a more appropriate nomenclature of “chronic enteropathy associated with SLCO2A1 gene” (CEAS). PMID:26539716

  3. Characterization of the interferon gamma response to Lawsonia intracellularis using an equine proliferative enteropathy challenge (EPE) model.

    PubMed

    Page, A E; Loynachan, A T; Bryant, U; Stills, H F; Adams, A A; Gebhart, C J; Pusterla, N; Horohov, D W

    2011-09-15

    Lawsonia intracellularis is the etiological agent of infectious intestinal hyperplasia for which several clinical diseases have been described including proliferative enteropathy (PE), intestinal adenomatosis, and ileitis. While initially recognized as the causative agent of PE in pigs, L. intracellularis is now viewed as an emerging cause of intestinal hyperplasia in a wide range of mammalian species, including horses. Equine proliferative enteropathy (EPE) has been reported worldwide though definitive diagnosis is difficult and the epidemiology of the disease remains poorly understood. Weanlings, in particular, appear to be most at risk for infection, though the reasons for their particular susceptibility is unknown. Using an infectious challenge model for EPE, we demonstrate that EPE, like porcine proliferative enteropathy, can exhibit three clinical forms: classical, subclinical and acute. Out of six pony weanlings, one developed signs of classic EPE, one developed acute EPE, and two developed subclinical EPE. Attempts to induce pharmacological stress through the use of dexamethasone failed to have any effect on outcome. Peripheral blood cells collected from those weanlings that developed clinical EPE exhibited decreased expression of interferon-gamma (IFN-γ) following in vitro stimulation with L. intracellularis. By contrast, those weanlings that did not develop clinical disease generated a robust IFN-γ response. These results indicate IFN-γ likely plays a significant role in protection from disease caused by L. intracellularis in the equid. PMID:21719114

  4. [Autoimmune pancreatitis as an element of autoimmune polyglandular syndrome].

    PubMed

    Dyrla, Przemysław; Nowak, Tomasz; Gil, Jerzy; Adamiec, Cezary; Bobula, Mariusz; Saracyn, Marek

    2016-05-26

    Autoimmune pancreatitis constantly belongs to diseases which often causes significant diagnostic problem and often runs out with surgical intervention as considered to be a pancreatic cancer. Important although usually underestimated problems are polyglandular syndromes, which may consist of autoimmune pancreatitis (AIP) problem as well. This case report is an example of autoimmune polyglandular syndrome (APS), which was connected with the surgical treatment with biliary bypass anastomosis because of the unresectable lesion in the head of pancreas. The definite remission of the pancreatic lesion finally came after a steroid therapy. Differentiation between neoplastic and inflammatory pancreatic tumors very often remains a serious clinical problem. On grounds of imaging and cytopathology exams it is often difficult to decide about the nature of a lesion. The negative result of cytopathological biopsy examination does not finally settle straightforward diagnosis. Diagnostic problems affect also autoimmune pancreatitis. It is worth to undertake attempts to differentiate pancreatic lesions especially in cases of concomitance with other autoimmune polyglandular syndromes. That is because it is connected with completely different treatment and outcome. We should remember about diagnostic criteria of autoimmune pancreatitis. Appropriate diagnosis for patients with AIP gives them a chance to avoid serious surgical resection and possible complications. PMID:27234865

  5. [Molecular diagnosis of autoimmune dermatoses].

    PubMed

    Hoffmann, K; Hertl, M; Sitaru, C

    2016-01-01

    Bullous autoimmune diseases are organ-specific disorders characterized by an autoantibody-mediated blistering of skin and mucous membranes. The detection of tissue-bound and serum autoantibodies is prerequisite for the diagnosis of autoimmune blistering diseases. The individual entities of this group may be difficult to differentiate on clinical grounds alone. An accurate diagnosis is however important for prognosis and therapy. A preliminary diagnostic step includes direct and indirect immunofluorescence microscopy, which provide information about the binding pattern and isotype of autoantibodies and allow the diagnosis of the autoimmune blistering disease. Subsequent characterization of the molecular specificity of autoantibodies is necessary for the exact classification of autoimmune bullous dermatoses. The quantitative measurement of autoantibodies against structural proteins of the skin may be often used to assess disease severity at follow-up. PMID:26612472

  6. Epigenetic alterations underlying autoimmune diseases.

    PubMed

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein

    2016-03-01

    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases. PMID:26761426

  7. American Autoimmune Related Diseases Association

    MedlinePlus

    ... Statistics Your source for autoimmune related disease information. **We need your input** We want to know of your experiences with Non- ... email address with us. Please be assured that we will always keep your email private. We will ...

  8. Sialic acids and autoimmune disease.

    PubMed

    Mahajan, Vinay S; Pillai, Shiv

    2016-01-01

    An important underlying mechanism that contributes to autoimmunity is the loss of inhibitory signaling in the immune system. Sialic acid-recognizing Ig superfamily lectins or Siglecs are a family of cell surface proteins largely expressed in hematopoietic cells. The majority of Siglecs are inhibitory receptors expressed in immune cells that bind to sialic acid-containing ligands and recruit SH2-domain-containing tyrosine phosphatases to their cytoplasmic tails. They deliver inhibitory signals that can contribute to the constraining of immune cells, and thus protect the host from autoimmunity. The inhibitory functions of CD22/Siglec-2 and Siglec-G and their contributions to tolerance and autoimmunity, primarily in the B lymphocyte context, are considered in some detail in this review. The relevance to autoimmunity and unregulated inflammation of modified sialic acids, enzymes that modify sialic acid, and other sialic acid-binding proteins are also reviewed. PMID:26683151

  9. Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity

    PubMed Central

    Zhong, Ze-yu; Sun, Bin-bin; Shu, Nan; Xie, Qiu-shi; Tang, Xian-ge; Ling, Zhao-li; Wang, Fan; Zhao, Kai-jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-zhu; Liu, Xiao-dong

    2016-01-01

    Aim: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. Methods: The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Results: Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestineenteropathy was developed with severe enteropathy occurred in distal small intestine. Co-administration of ciprofloxacin significantly alleviated diclofenac-induced enteropathy. Conclusion: Co-administration of ciprofloxacin attenuated enterohepatic circulation of diclofenac and alleviated diclofenac-induced enteropathy in rats, partly via

  10. A case of protein supplement effect in protein-losing enteropathy.

    PubMed

    Lee, Hyun Jeong; Rha, Mi Yong; Cho, Young Yun; Kim, Eun Ran; Chang, Dong Kyung

    2012-07-01

    The objective of this article is to report improvement of nutritional status by protein supplements in the patient with protein-losing enteropathy. The patient was a female whose age was 25 and underwent medical treatment of Crohn's disease, an inflammatory bowl disease, after diagnosis of cryptogenic multifocal ulcerous enteritis. The weight was 33.3 kg (68% of IBW) in the severe underweight and suffered from ascites and subcutaneous edema with hypoalbuminemia (1.3 g/dL) at the time of hospitalization. The patient consumed food restrictively due to abdominal discomfort. Despite various attempts of oral feeding, the levels of calorie and protein intake fell into 40-50% of the required amount, which was 800-900 kcal/d (24-27 kcal/kg/d) for calorie and 34 g/d (1 g/kg/d) for protein. It was planned to supplement the patient with caloric supplementation (40-50 kcal/kg) and protein supplementation (2.5 g/kg) to increase body weight and improve hypoproteinemia. It was also planned to increase the level of protein intake slowly to target 55 g/d in about 2 weeks starting from 10 g/d and monitored kidney load with high protein supplementation. The weight loss was 1.0 kg when the patient was discharged from the hospital (hospitalization periods of 4 weeks), however, serum albumin was improved from 1.3 g/dL to 2.5 g/dL and there was no abdominal discomfort. She kept supplement of protein at 55 g/d for 5 months after the discharge from the hospital and kept it at 35 g/d for about 2 months and then 25 g/d. The body weight increased gradually from 32.3 kg (65% of IBW) to 44.0 kg (89% of IBW) by 36% for the period of F/u and serum albumin was kept above 2.8 g/dL without intravenous injection of albumin. The performance status was improved from 4 points of 'very tired' to 2 points of 'a little tired' out of 5-point scale measurement and the use of diuretic stopped from the time of 4th month after the discharge from the hospital owing to improvement in edema and ascites. During

  11. Autoimmune sleep disorders.

    PubMed

    Silber, Michael H

    2016-01-01

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

  12. Autoimmune and inflammatory epilepsies.

    PubMed

    Nabbout, Rima

    2012-09-01

    The role of immunity and inflammation in epilepsy have long been suggested by the anticonvulsant activity of steroids in some infancy and childhood epilepsies. The role of fever and infection in exacerbating seizures due to possible proinflammatory molecules, the increased frequency of seizures in systemic autoimmune diseases like systemic lupus erythematous, and, recently, the detection of autoantibodies in some unexplained epilepsies reinforced the causal place of immunity and inflammation in epilepsies with unknown etiology. In this article, we summarize epilepsies where clinical and biologic data strongly support the pathogenic role of autoantibodies (e.g., limbic encephalitides, N-methyl-d-aspartate [NMDA] encephalitis) and epilepsies where immune-mediated inflammation occurs, but the full pathogenic cascade is either not clear (e.g., Rasmussen's encephalitis) or only strongly hypothesized (idiopathic hemiconvulsion-hemiplegia syndrome [IHHS] and fever-induced refractory epilepsy in school-aged children [FIRES]). We emphasize the electroclinical features that would help to diagnose these conditions, allowing early immunomodulating therapy. Finally, we raise some questions that remain unclear regarding diagnosis, mechanisms, and future therapies. PMID:22946722

  13. Progesterone and Autoimmune Disease

    PubMed Central

    Hughes, Grant C.

    2011-01-01

    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-α) 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

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

    PubMed Central

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

    2015-01-01

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

  15. Successful therapy for protein-losing enteropathy caused by chronic neuronopathic Gaucher disease

    PubMed Central

    Mhanni, A.A.; Kozenko, M.; Hartley, J.N.; Deneau, M.; El-Matary, W.; Rockman-Greenberg, C.

    2015-01-01

    Gaucher disease (OMIM #230800) is caused by β-glucosidase deficiency and primarily involves the mononuclear phagocyte system (also called Reticuloendothelial System or Macrophage System). The disease is classified into three main phenotypes based on the presence or absence of neurological manifestations: non-neuronopathic (type 1), acute neuronopathic (type 2) and chronic neuronopathic (type 3). Typical manifestations include hepatosplenomegaly, skeletal deformities, hematological abnormalities, interstitial lung fibrosis and neurodegeneration in neuronopathic cases. Mesenteric lymphadenopathy with resultant protein losing enteropathy (PLE) has only been rarely described. Mesenteric lymphadenopathy may lead to intestinal lymphatic obstruction and secondary lymphangiectasia resulting in chronic diarrhea, abdominal pain and weight loss. Fecal protein loss with secondary hypoalbuminemia can be significant. We report a male with Chronic Neuronopathic Gaucher disease (GD) (homozygous for c.1448T > C (NM_000157.3) GBA mutation) who at 16 years of age developed intractable abdominal pain, diarrhea and weight loss. This was caused by PLE secondary to intestinal lymphangiectasia caused by calcified mesenteric lymphadenopathy despite prior long term enzyme replacement therapy (ERT) and/or substrate reduction therapy (SRT). His older similarly affected sister who had been receiving treatment with ERT and/or SRT remains stable on these treatments with no evidence of mesenteric lymphadenopathy. Medical management with total parenteral nutrition, daily medium chain triglyceride-oil (MCT) supplementation, low dose oral budesonide, continued oral SRT and an increased dose of parenteral ERT has stabilized his condition with resolution of the gastrointestinal symptoms and appropriate weight gain. PMID:27014572

  16. Protein-losing enteropathy cured by resection of adenomatous goiter: report of a case.

    PubMed

    Takada, Jun; Araki, Hiroshi; Kubota, Masaya; Ibuka, Takashi; Shiraki, Makoto; Shimizu, Masahito; Moriwaki, Hisataka

    2015-06-01

    A 51-year-old Japanese woman presented to our hospital with systemic edema and general fatigue. Her serum albumin level was very low (1.5 g/dL). Technetium-99 m-human serum albumin ((99m)Tc-HSA) scintigraphy showed albumin leakage from the upper small bowel. Magnetic resonance lymphangiography showed dilated lymphatic vessels in the chest, whereas double-balloon enteroscopy (DBE) showed white villi and chyle leakage in the deeper part of the duodenal mucosa. A duodenal mucosa biopsy specimen revealed lymphangiectasia. She was diagnosed with protein-losing enteropathy (PLE). Treatment with a fat-restricted diet and tranexamic acid--previously reported to be effective against PLE--was attempted, but was ineffective. A thyroid tumor was simultaneously detected in her left neck, and was found to extend to the mediastinum on computed tomography. The tumor (size, >5 cm) was resected, and a pathological diagnosis of adenomatous goiter was made. The patient's serum albumin level increased to normal levels within 1 month postoperatively. After 6 months, (99m)Tc-HSA scintigraphy showed no albumin leakage from the gastrointestinal tract, and disappearance of white villi and chyle leakage on DBE. No lymphangiectasia was noted in the biopsy specimen. Adenomatous goiter was thus considered the cause of the PLE, possibly through lymph flow obstruction in the mediastinum. PMID:25845937

  17. Congenital protein losing enteropathy: an inborn error of lipid metabolism due to DGAT1 mutations.

    PubMed

    Stephen, Joshi; Vilboux, Thierry; Haberman, Yael; Pri-Chen, Hadass; Pode-Shakked, Ben; Mazaheri, Sina; Marek-Yagel, Dina; Barel, Ortal; Di Segni, Ayelet; Eyal, Eran; Hout-Siloni, Goni; Lahad, Avishay; Shalem, Tzippora; Rechavi, Gideon; Malicdan, May Christine V; Weiss, Batia; Gahl, William A; Anikster, Yair

    2016-08-01

    Protein-losing enteropathy (PLE) is a clinical disorder of protein loss from the gastrointestinal system that results in hypoproteinemia and malnutrition. This condition is associated with a wide range of gastrointestinal disorders. Recently, a unique syndrome of congenital PLE associated with biallelic mutations in the DGAT1 gene has been reported in a single family. We hypothesize that mutations in this gene are responsible for undiagnosed cases of PLE in infancy. Here we investigated three children in two families presenting with severe diarrhea, hypoalbuminemia and PLE, using clinical studies, homozygosity mapping, and exome sequencing. In one family, homozygosity mapping using SNP arrays revealed the DGAT1 gene as the best candidate gene for the proband. Sequencing of all the exons including flanking regions and promoter regions of the gene identified a novel homozygous missense variant, p.(Leu295Pro), in the highly conserved membrane-bound O-acyl transferase (MBOAT) domain of the DGAT1 protein. Expression studies verified reduced amounts of DGAT1 in patient fibroblasts. In a second family, exome sequencing identified a previously reported splice site mutation in intron 8. These cases of DGAT1 deficiency extend the molecular and phenotypic spectrum of PLE, suggesting a re-evaluation of the use of DGAT1 inhibitors for metabolic disorders including obesity and diabetes. PMID:26883093

  18. Changes in cecal microbiota and mucosal gene expression revealed new aspects of epizootic rabbit enteropathy.

    PubMed

    Bäuerl, Christine; Collado, M Carmen; Zúñiga, Manuel; Blas, Enrique; Pérez Martínez, Gaspar

    2014-01-01

    Epizootic Rabbit Enteropathy (ERE) is a severe disease of unknown aetiology that mainly affects post-weaning animals. Its incidence can be prevented by antibiotic treatment suggesting that bacterial elements are crucial for the development of the disease. Microbial dynamics and host responses during the disease were studied. Cecal microbiota was characterized in three rabbit groups (ERE-affected, healthy and healthy pretreated with antibiotics), followed by transcriptional analysis of cytokines and mucins in the cecal mucosa and vermix by q-rtPCR. In healthy animals, cecal microbiota with or without antibiotic pretreatment was very similar and dominated by Alistipes and Ruminococcus. Proportions of both genera decreased in ERE rabbits whereas Bacteroides, Akkermansia and Rikenella increased, as well as Clostridium, γ-Proteobacteria and other opportunistic and pathogenic species. The ERE group displayed remarkable dysbiosis and reduced taxonomic diversity. Transcription rate of mucins and inflammatory cytokines was very high in ERE rabbits, except IL-2, and its analysis revealed the existence of two clearly different gene expression patterns corresponding to Inflammatory and (mucin) Secretory Profiles. Furthermore, these profiles were associated to different bacterial species, suggesting that they may correspond to different stages of the disease. Other data obtained in this work reinforced the notion that ERE morbidity and mortality is possibly caused by an overgrowth of different pathogens in the gut of animals whose immune defence mechanisms seem not to be adequately responding. PMID:25147938

  19. Changes in Cecal Microbiota and Mucosal Gene Expression Revealed New Aspects of Epizootic Rabbit Enteropathy

    PubMed Central

    Zúñiga, Manuel; Blas, Enrique; Pérez Martínez, Gaspar

    2014-01-01

    Epizootic Rabbit Enteropathy (ERE) is a severe disease of unknown aetiology that mainly affects post-weaning animals. Its incidence can be prevented by antibiotic treatment suggesting that bacterial elements are crucial for the development of the disease. Microbial dynamics and host responses during the disease were studied. Cecal microbiota was characterized in three rabbit groups (ERE-affected, healthy and healthy pretreated with antibiotics), followed by transcriptional analysis of cytokines and mucins in the cecal mucosa and vermix by q-rtPCR. In healthy animals, cecal microbiota with or without antibiotic pretreatment was very similar and dominated by Alistipes and Ruminococcus. Proportions of both genera decreased in ERE rabbits whereas Bacteroides, Akkermansia and Rikenella increased, as well as Clostridium, γ-Proteobacteria and other opportunistic and pathogenic species. The ERE group displayed remarkable dysbiosis and reduced taxonomic diversity. Transcription rate of mucins and inflammatory cytokines was very high in ERE rabbits, except IL-2, and its analysis revealed the existence of two clearly different gene expression patterns corresponding to Inflammatory and (mucin) Secretory Profiles. Furthermore, these profiles were associated to different bacterial species, suggesting that they may correspond to different stages of the disease. Other data obtained in this work reinforced the notion that ERE morbidity and mortality is possibly caused by an overgrowth of different pathogens in the gut of animals whose immune defence mechanisms seem not to be adequately responding. PMID:25147938

  20. Cholestasis and protein-losing enteropathy secondary to hyperthyroidism in a 6-year-old girl.

    PubMed

    Gargouri, Lamia; Charfi, Manel; Maalej, Bayen; Majdoub, Imen; Safi, Faiza; Fourati, Hela; Hentati, Yosr; Daoud, Emna; Mnif, Zeineb; Abid, Mohamed; Mahfoudh, Abdelmajid

    2014-09-01

    Hepatic dysfunctions are not infrequent in patients with hyperthyroidism. These disorders may be related to the effects of the excess thyroid hormone secretion, to the uses of antithyroid drugs, or to the presence of concomitant hepatic diseases. Our aim is to describe the clinical and biochemical features of liver dysfunction related to thyrotoxicosis. We report here a case of a 6-year-old girl who was admitted for jaundice and pruritus as a result of the development of hyperthyroidism due to Graves' disease. On physical examination at admission, she was found to have jaundice and hepatomegaly. Laboratory data show cholestasis and protein-losing enteropathy. Investigations exclude other causes of hepatic disorder. One month after the initiation of antithyroid drug, the patient became euthyroid with improvement in jaundice and pruritus and normalization of hepatic tests and alpha antitrypsine clearance. In conclusion, the diagnosis of hyperthyroidism may be delayed in patients in whom the primary manifestations were pruritus and jaundice. The physician should suspect thyrotoxicosis prior to hepatitis or skin manifestations. PMID:24825088

  1. [Isolated central nervous system relapse in type II enteropathy-associated T cell lymphoma].

    PubMed

    Nishida, Hiroko; Endo, Kiyoshi; Hatano, Mami; Tatekawa, Nobuo; Mashima, Eri; Hashida, Risa; Hori, Masao; Obara, Katsuyuki

    2015-06-01

    A 75-year-old male presented with progressive lower abdominal discomfort. CT scan demonstrated hypertrophy of the intestinal wall, small bowel dilatation, and masses in the descending colon. Biopsy specimens of the jejunum and descending colon revealed widespread distribution of medium-sized atypical lymphocytes with an immunophenotype, positivity for CD3, CD8, CD56, TAI-1, granzyme B and TCRβ, but negativity for CD4, CD5, CD20, CD30 and EBER-ISH. Type II enteropathy-associated T cell lymphoma (EATL; Lugano, stage IIE) was diagnosed. Subsequently, he received 6 cycles of chemotherapy with 2/3 dose CHOP and obtained complete remission. However, 18 months after the initial presentation, he presented with rapidly progressive mental deterioration. Gadolinium enhanced T1-weighted brain MR images showed multiple masses with mild heterogeneous enhancement. Brain biopsy revealed necrotic tumors composed of medium-sized atypical lymphocytes, positive for CD3, CD8, CD56, TIA-1, granzyme B and TCRβ, but negative for CD4, CD20, and EBER-ISH. CT scan disclosed no evidence of systemic lymphoma relapse, indicating central nervous system relapse of EATL. Despite immediate high-dose chemotherapy with methotrexate, he died of disease progression. EATL is a rare disease with a very poor outcome, for which a validated standard treatment is still lacking. Further studies are needed to identify innovative therapies for treating EATL. PMID:26256881

  2. Protein-losing enteropathy in a patient with familial adenomatous polyposis and advanced colon cancer.

    PubMed

    Miyamoto, Yoshihiko; Muguruma, Naoki; Kimura, Tetsuo; Okamoto, Koichi; Sogabe, Masahiro; Miyamoto, Hiroshi; Kohno, Seiya; Nakasono, Masahiko; Hayashi, Hiroshige; Bando, Yoshimi; Takayama, Tetsuji

    2016-06-01

    A 29-year-old female visited a hospital because of increasingly severe lower leg edema. She was diagnosed as having multiple polyps in the stomach and colon by gastroscopy and sigmoidoscopy as well as multiple liver tumors by abdominal CT. She was referred to our hospital for further examination. Total colonoscopy revealed a type 2 tumor in the transverse colon and more than 200 polyps distributed throughout the colorectum. Biopsies of the tumor and polyps showed histological characteristics of adenocarcinoma and tubulovillous adenoma, respectively. Thus, she was diagnosed as having metastatic colon cancer derived from familial adenomatous polyposis (FAP). Laboratory tests showed a marked hypoalbuminemia of 1.1 g/dl. The fecal alpha-1 anti-trypsin test showed abnormal clearance (62.1 ml/day), and scintigraphy using 99mTc-human serum albumin revealed protein loss in the whole colon. Multiple ligation probe amplification analysis of the APC gene identified a germline duplication of exons 11-13. Direct sequencing of the reverse transcription PCR products of APC mRNA revealed a deletion of 25 base pairs and a tandem duplication of exons 11-13. This case was considered to be protein-losing enteropathy resulting from numerous colonic tubulovillous adenomas and advanced colon cancer in a FAP patient with unusual mutational events in APC. PMID:27170298

  3. Water, sanitation, and hygiene (WASH), environmental enteropathy, nutrition, and early child development: making the links.

    PubMed

    Ngure, Francis M; Reid, Brianna M; Humphrey, Jean H; Mbuya, Mduduzi N; Pelto, Gretel; Stoltzfus, Rebecca J

    2014-01-01

    There is scarce research and programmatic evidence on the effect of poor water, sanitation, and hygiene (WASH) conditions of the physical environment on early child cognitive, sensorimotor, and socioemotional development. Furthermore, many common WASH interventions are not specifically designed to protect babies in the first 3 years of life, when gut health and linear growth are established. We review evidence linking WASH, anemia, and child growth, and highlight pathways through which WASH may affect early child development, primarily through inflammation, stunting, and anemia. Environmental enteropathy, a prevalent subclinical condition of the gut, may be a key mediating pathway linking poor hygiene to developmental deficits. Current early child development research and programs lack evidence-based interventions to provide a clean play and infant feeding environment in addition to established priorities of nutrition, stimulation, and child protection. Solutions to this problem will require appropriate behavior change and technologies that are adapted to the social and physical context and conducive to infant play and socialization. We propose the concept of baby WASH as an additional component of early childhood development programs. PMID:24571214

  4. Protein-losing enteropathy in a dog with lymphangiectasia, lymphoplasmacytic enteritis and pancreatic exocrine insufficiency.

    PubMed

    Rodríguez-Alarcón, C A; Beristaín-Ruiz, D M; Pérez-Casio, F; Rivera, R; Ochoa, G; Martín-Orozco, U

    2012-01-01

    This is a report of seven-year-old male Akita mixed dog, with protein-losing enteropathy (PLE). He had a history of chronic vomiting and diarrhea with anorexia/hyporexia. Previously he suffered acute abdomen about eight months prior to this visit. Our dog showed uncommon combination of diseases that could cause PLE since it was affected by inflammatory bowel disease (IBD), intestinal lymphangiectasia (IL), and exocrine pancreatic insufficiency (EPI). The dog had most of the abnormalities found in IL, as well as hypoalbuminemia, hyperglobulinemia, lymphopenia, hypocalcemia, and hypercholesterolemia. During endoscopy exam, we found changes characteristic of IL such as irregular small white spots. We took biopsies from stomach, duodenum, and cecum. These biopsies showed infiltration by lymphocytes and plasmatic cells in the lamina propria also, the duodenal biopsies showed moderate dilation of the lymphatic vessels. The patient had 2.1 µg/mL of TLI, this result was compatible with EPI. We assume that the first pathology in this animal was IBD, which caused chronic pancreatitis (CP) that in turn progressed to EPI. It is also possible that IL was secondary to IBD. We have reported for the first time the correlation of IBD and EPI in dogs. This should change our approach to treating chronic diarrhea in dogs. Therefore, we propose that dogs diagnosed with EPI should also be subjected to endoscopy and intestinal biopsy. Similarly, to rule out secondary EPI, TLI should be measured routinely in dogs with IBD. PMID:23106499

  5. Assessment of Environmental Enteropathy in the MAL-ED Cohort Study: Theoretical and Analytic Framework

    PubMed Central

    Kosek, Margaret; Guerrant, Richard L.; Kang, Gagandeep; Bhutta, Zulfiqar; Yori, Pablo Peñataro; Gratz, Jean; Gottlieb, Michael; Lang, Dennis; Lee, Gwenyth; Haque, Rashidul; Mason, Carl J.; Ahmed, Tahmeed; Lima, Aldo; Petri, William A.; Houpt, Eric; Olortegui, Maribel Paredes; Seidman, Jessica C.; Mduma, Estomih; Samie, Amidou; Babji, Sudhir

    2014-01-01

    Individuals in the developing world live in conditions of intense exposure to enteric pathogens due to suboptimal water and sanitation. These environmental conditions lead to alterations in intestinal structure, function, and local and systemic immune activation that are collectively referred to as environmental enteropathy (EE). This condition, although poorly defined, is likely to be exacerbated by undernutrition as well as being responsible for permanent growth deficits acquired in early childhood, vaccine failure, and loss of human potential. This article addresses the underlying theoretical and analytical frameworks informing the methodology proposed by the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study to define and quantify the burden of disease caused by EE within a multisite cohort. Additionally, we will discuss efforts to improve, standardize, and harmonize laboratory practices within the MAL-ED Network. These efforts will address current limitations in the understanding of EE and its burden on children in the developing world. PMID:25305293

  6. Assessment of environmental enteropathy in the MAL-ED cohort study: theoretical and analytic framework.

    PubMed

    Kosek, Margaret; Guerrant, Richard L; Kang, Gagandeep; Bhutta, Zulfiqar; Yori, Pablo Peñataro; Gratz, Jean; Gottlieb, Michael; Lang, Dennis; Lee, Gwenyth; Haque, Rashidul; Mason, Carl J; Ahmed, Tahmeed; Lima, Aldo; Petri, William A; Houpt, Eric; Olortegui, Maribel Paredes; Seidman, Jessica C; Mduma, Estomih; Samie, Amidou; Babji, Sudhir

    2014-11-01

    Individuals in the developing world live in conditions of intense exposure to enteric pathogens due to suboptimal water and sanitation. These environmental conditions lead to alterations in intestinal structure, function, and local and systemic immune activation that are collectively referred to as environmental enteropathy (EE). This condition, although poorly defined, is likely to be exacerbated by undernutrition as well as being responsible for permanent growth deficits acquired in early childhood, vaccine failure, and loss of human potential. This article addresses the underlying theoretical and analytical frameworks informing the methodology proposed by the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study to define and quantify the burden of disease caused by EE within a multisite cohort. Additionally, we will discuss efforts to improve, standardize, and harmonize laboratory practices within the MAL-ED Network. These efforts will address current limitations in the understanding of EE and its burden on children in the developing world. PMID:25305293

  7. Successful therapy for protein-losing enteropathy caused by chronic neuronopathic Gaucher disease.

    PubMed

    Mhanni, A A; Kozenko, M; Hartley, J N; Deneau, M; El-Matary, W; Rockman-Greenberg, C

    2016-03-01

    Gaucher disease (OMIM #230800) is caused by β-glucosidase deficiency and primarily involves the mononuclear phagocyte system (also called Reticuloendothelial System or Macrophage System). The disease is classified into three main phenotypes based on the presence or absence of neurological manifestations: non-neuronopathic (type 1), acute neuronopathic (type 2) and chronic neuronopathic (type 3). Typical manifestations include hepatosplenomegaly, skeletal deformities, hematological abnormalities, interstitial lung fibrosis and neurodegeneration in neuronopathic cases. Mesenteric lymphadenopathy with resultant protein losing enteropathy (PLE) has only been rarely described. Mesenteric lymphadenopathy may lead to intestinal lymphatic obstruction and secondary lymphangiectasia resulting in chronic diarrhea, abdominal pain and weight loss. Fecal protein loss with secondary hypoalbuminemia can be significant. We report a male with Chronic Neuronopathic Gaucher disease (GD) (homozygous for c.1448T > C (NM_000157.3) GBA mutation) who at 16 years of age developed intractable abdominal pain, diarrhea and weight loss. This was caused by PLE secondary to intestinal lymphangiectasia caused by calcified mesenteric lymphadenopathy despite prior long term enzyme replacement therapy (ERT) and/or substrate reduction therapy (SRT). His older similarly affected sister who had been receiving treatment with ERT and/or SRT remains stable on these treatments with no evidence of mesenteric lymphadenopathy. Medical management with total parenteral nutrition, daily medium chain triglyceride-oil (MCT) supplementation, low dose oral budesonide, continued oral SRT and an increased dose of parenteral ERT has stabilized his condition with resolution of the gastrointestinal symptoms and appropriate weight gain. PMID:27014572

  8. Chronic autoimmune thyroid disease.

    PubMed

    Litta Modignani, R; Barantani, E; Mazzolari, M; Pincetti Nervi, M; Macchi, R

    1991-01-01

    A total of 67 patients with chronic autoimmune thyroid disease were followed, mainly as outpatients, for a period of a few months to over 15 years. The diagnosis was euthyroidism (n = 16, 23.8%), subclinical hypothyroidism (n = 20, 29.8%), primary hypothyroidism (n = 28, 41.7%) or hashitoxicosis (n = 3, 4.47%). Patients with goiters fit Hashimoto's original description of "struma lymphomatosa". The diagnosis was made on clinical grounds and the usual laboratory hormonal tests. Histological examination was carried out at surgery or by fine needle aspiration in 35 patients (52.2%), and a clinical diagnosis was made in 32 (47.7%). Three patients had juvenile Hashimoto's thyroiditis. Most patients were in the fourth, fifth or sixth decade (64.8%), and of these 12 (18%) had subclinical hypothyroidism, which should be suspected when thyrotropin (TSH) is twice the upper normal limit. In these cases thyrotropin releasing hormone (TRH) testing and evaluation of anti-thyroglobulin antibodies (TgAb) and anti-microsomal antigen antibodies (MsAb) are mandatory. Hypothyroidism with few symptoms develops insidiously in young or elderly patients; the most sensitive test is TSH assay in conjunction with tests for TgAb and MsAb. L-thyroxine administration may be harmful in older patients with late diagnosed primary hypothyroidism. Thyroid supplementation is suggested for patients with subclinical hypothyroidism if TSH values are above 10 mU/L; otherwise they should be followed up annually, as should patients with positive thyroid autoantibodies who are still euthyroid. PMID:1804288

  9. Estrogens and autoimmune diseases.

    PubMed

    Cutolo, Maurizio; Capellino, Silvia; Sulli, Alberto; Serioli, Bruno; Secchi, Maria Elena; Villaggio, Barbara; Straub, Rainer H

    2006-11-01

    Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors . Several physiological, pathological, and therapeutic conditions may change the serum estrogen milieu and/or peripheral conversion rate, including the menstrual cycle, pregnancy, postpartum period, menopause, being elderly, chronic stress, altered circadian rhythms, inflammatory cytokines, and use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. In particular, cortisol and melatonin circadian rhythms are altered, at least in rheumatoid arthritis (RA), and partially involve sex hormone circadian synthesis and levels as well. Abnormal regulation of aromatase activity (i.e., increased activity) by inflammatory cytokine production (i.e., TNF-alpha, IL-1, and IL-6) may partially explain the abnormalities of peripheral estrogen synthesis in RA (i.e., increased availability of 17-beta estradiol and possible metabolites in synovial fluids) and in systemic lupus erythematosus, as well as the altered serum sex-hormone levels and ratio (i.e., decreased androgens and DHEAS). In the synovial fluids of RA patients, the increased estrogen concentration is observed in both sexes and is more specifically characterized by the hydroxylated forms, in particular 16alpha-hydroxyestrone, which is a mitogenic and cell proliferative endogenous hormone. Local effects of sex hormones in autoimmune rheumatic diseases seems to consist mainly in modulation of cell proliferation and cytokine production (i.e., TNF-alpha, Il-1, IL-12). In this respect, it is interesting that male patients with RA seem to profit more from anti-TNFalpha strategies than do female patients. PMID:17261796

  10. Autoimmune hemolytic anemia: classification and therapeutic approaches.

    PubMed

    Sève, Pascal; Philippe, Pierre; Dufour, Jean-François; Broussolle, Christiane; Michel, Marc

    2008-12-01

    Autoimmune hemolytic anemia (AIHA) is a relatively uncommon cause of anemia. Classifications of AIHA include warm AIHA, cold AIHA (including mainly chronic cold agglutinin disease and paroxysmal cold hemoglobinuria), mixed-type AIHA and drug-induced AIHA. AIHA may also be further subdivided on the basis of etiology. Management of AIHA is based mainly on empirical data and on small, retrospective, uncontrolled studies. The therapeutic options for treating AIHA are increasing with monoclonal antibodies and, potentially, complement inhibitory drugs. Based on data available in the literature and our experience, we propose algorithms for the treatment of warm AIHA and cold agglutinin disease in adults. Therapeutic trials are needed in order to better stratify treatment, taking into account the promising efficacy of rituximab. PMID:21082924

  11. [Retinoid therapy for autoimmune diseases].

    PubMed

    Fukasawa, Hiroshi; Kagechika, Hiroyuki; Shudo, Koichi

    2006-06-01

    Retinoid is a collective term for compounds which bind to and activate retinoic acid receptors (RARalpha, beta, gamma and RXRalpha, beta, gamma), members of nuclear hormone receptor superfamily. The most important endogeneous retinoid is all-trans-retinoic acid (ATRA) which is an RARalpha, beta and gamma ligand. ATRA and its mimics have been in clinical use for treatment of acute promyelocytic leukemia (APL) and some skin diseases. Many synthetic retinoids have been developed and attempts to improve their medicinal properties have been made. Among them, tamibarotene (Am80) is an RARalpha- and RARbeta-specific (but RARgamma- and RXRs-nonbinding) synthetic retinoid that is effective in the treatment of psoriasis patients and relapsed APL. Experimentally, this compound is also active in animal models of rheumatoid arthritis and experimental autoimmune encephalomyelitis. On this background, possible application of retinoids for the treatment of autoimmune diseases was discussed. In particular, Th1 dominant autoimmune diseases may be the targets of the retinoids. PMID:16819260

  12. [Bullous autoimmune disorders in children].

    PubMed

    Sárdy, M; Kasperkiewicz, M

    2013-06-01

    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

  13. Free radical theory of autoimmunity

    PubMed Central

    Kannan, Subburaj

    2006-01-01

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

  14. [Infectious agents and autoimmune diseases].

    PubMed

    Riebeling-Navarro, C; Madrid-Marina, V; Camarena-Medellín, B E; Peralta-Zaragoza, O; Barrera, R

    1992-01-01

    In this paper the molecular aspects of the relationships between infectious agents and autoimmune diseases, the mechanisms of immune response to infectious agents, and the more recent hypotheses regarding the cause of autoimmune diseases are discussed. The antigens are processed and selected by their immunogenicity, and presented by HLA molecules to the T cell receptor. These events initiate the immune response with the activation and proliferation of T-lymphocytes. Although there are several hypotheses regarding the cause of autoimmune diseases and too many findings against and in favor of them, there is still no conclusive data. All these hypothesis and findings are discussed in the context of the more recent advances. PMID:1615352

  15. Thyroid dysfunction: an autoimmune aspect.

    PubMed

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

    2015-01-01

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

  16. Viruses, cytokines, antigens, and autoimmunity.

    PubMed Central

    Gianani, R; Sarvetnick, N

    1996-01-01

    To explain the pathogenesis of autoimmunity, we hypothesize that following an infection the immune response spreads to tissue-specific autoantigens in genetically predisposed individuals eventually determining progression to disease. Molecular mimicry between viral and self antigens could, in some instances, initiate autoimmunity. Local elicitation of inflammatory cytokines following infection probably plays a pivotal role in determining loss of functional tolerance to self autoantigens and the destructive activation of autoreactive cells. We also describe the potential role of interleukin 10, a powerful B-cell activator, in increasing the efficiency of epitope recognition, that could well be crucial to the progression toward disease. PMID:8637859

  17. Autoimmune myasthenia gravis.

    PubMed

    Jayawant, Sandeep; Parr, Jeremy; Vincent, Angela

    2013-01-01

    Myasthenia gravis in children can be generalized or ocular, and associated with antibodies to acetylcholine receptors or muscle-specific kinase, but it can be negative for those antibodies (seronegative). It needs to be distinguished from congenital myasthenic syndromes and other neuromuscular diseases. In the perinatal period, transient neonatal myasthenia and arthrogryposis multiplex congenita, due to maternal antibodies, need to be considered. Juvenile myasthenia is similar in presentation and treatment to that in adults. Here we present guidelines for recognition, diagnosis, and treatment. PMID:23622368

  18. Shaking Out Clues to Autoimmune Disease

    MedlinePlus

    ... of Autoimmunity-Causing T Cells Landmark Analysis Probes Nature vs. Nurture in Multiple Sclerosis Understanding Autoimmune Diseases Immune Cells Reference: Nature. 2013 Mar 6. doi: 10.1038/nature11981. [Epub ...

  19. Association between faecal load of lawsonia intracellularis and pathological findings of proliferative enteropathy in pigs with diarrhoea

    PubMed Central

    2012-01-01

    Background The study was designed to investigate correlation between histological findings of Lawsonia intracellularis in porcine cases of diarrhoea and the quantitative detection of Lawsonia intracellularis in faeces. A total of 156 pigs (10 to 70 days post weaning) with diarrhoea were randomly selected from 20 herds: The pigs were subjected to necropsy, histopathology, immunohistochemistry and faecal quantification of Lawsonia intracellularis by real time PCR. Results The median Lawsonia intracellularis excretion was significantly higher in pigs with gross lesions of proliferative enteropathy (median excretion: 5.92 log10 bacteria/g faeces) compared to pigs without gross lesions of proliferative enteropathy (median excretion: <3.3 log10 bacteria/g faeces) (P<0.001). Spearman’s correlation coefficient between the measureable PE lesions and L. intracellularis excretion was 0.50 (P<0.001). A significantly increasing trend in Lawsonia intracellularis excretion level for increasing proliferative enteropathy histopathology and immunohistochemistry scores was demonstrated (P<0.001; P<0.001). Spearman’s correlation coefficient between the histopathology scores and L. intracellularis excretion was 0.67 (P<0.001). Spearman’s correlation coefficient between the IHC scores and L. intracellularis excretion was 0.77 (P<0.001). Conclusions The histological and quantitative PCR detection of Lawsonia intracellularis were correlated in pigs with diarrhoea. Overall the results suggest that clinically important levels for Lawsonia intracellularis excretion in faeces may be established. Such clinical threshold levels may be used in practice to confirm a diagnosis of Lawsonia intracellularis associated diarrhoea. PMID:23092367

  20. Alterations of the Ileal and Colonic Mucosal Microbiota in Canine Chronic Enteropathies

    PubMed Central

    Cassmann, Eric; White, Robin; Atherly, Todd; Wang, Chong; Sun, Yaxuan; Khoda, Samir; Mosher, Curtis; Ackermann, Mark; Jergens, Albert

    2016-01-01

    Background The intestinal microbiota is increasingly linked to the pathogenesis of chronic enteropathies (CE) in dogs. While imbalances in duodenal and fecal microbial communities have been associated with mucosal inflammation, relatively little is known about alterations in mucosal bacteria seen with CE involving the ileum and colon. Aim To investigate the composition and spatial organization of mucosal microbiota in dogs with CE and controls. Methods Tissue sections from endoscopic biopsies of the ileum and colon from 19 dogs with inflammatory bowel disease (IBD), 6 dogs with granulomatous colitis (GC), 12 dogs with intestinal neoplasia, and 15 controls were studied by fluorescence in situ hybridization (FISH) on a quantifiable basis. Results The ileal and colonic mucosa of healthy dogs and dogs with CE is predominantly colonized by bacteria localized to free and adherent mucus compartments. CE dogs harbored more (P < 0.05) mucosal bacteria belonging to the Clostridium-coccoides/Eubacterium rectale group, Bacteroides, Enterobacteriaceae, and Escherichia coli versus controls. Within the CE group, IBD dogs had increased (P < 0.05) Enterobacteriaceae and E. coli bacteria attached onto surface epithelia or invading within the intestinal mucosa. Bacterial invasion with E. coli was observed in the ileal and colonic mucosa of dogs with GC (P < 0.05). Dogs with intestinal neoplasia had increased (P < 0.05) adherent (total bacteria, Enterobacteriaceae, E. coli) and invasive (Enterobacteriaceae, E. coli, and Bacteroides) bacteria in biopsy specimens. Increased numbers of total bacteria adherent to the colonic mucosa were associated with clinical disease severity in IBD dogs (P < 0.05). Conclusion Pathogenic events in canine CE are associated with different populations of the ileal and colonic mucosal microbiota. PMID:26840462

  1. IgA-containing circulating immune complexes in gluten-sensitive enteropathy

    PubMed Central

    Hall, R. P.; Strober, W.; Katz, S. I.; Lawley, T. J.

    1981-01-01

    Since mucosal immune response involving IgA may be particularly important in the pathogenesis of gluten-sensitive enteropathy (GSE), we examined the sera of 22 patients with GSE for IgA-containing circulating immune complexes using a sensitive radioimmunoassay, the Raji cell assay for IgA-containing circulating immune complexes. The Raji cell assay for IgG-containing circulating immune complexes and the 125I-C1q-binding assay were also used to measure IgG- or IgM-containing circulating immune complexes in these patients. Ten of 22 (45%) patients had IgA-containing circulating immune complexes, while 11 of 22 (50%) had IgG- or IgM-containing circulating immune complexes. Thirteen of 22 (59%) patients had circulating immune complexes detected by at least one of the assays used. Neither the presence nor level of immune complexes correlated with disease activity in any of the patients studied. Five patients, whose disease was well controlled on a gluten-free diet, were studied serially during dietary challenge with gluten. It was found that IgA-containing circulating immune complexes did not develop or increase in amount in the serum of these patients despite the induction of gastrointestinal symptoms. In addition, no significant change in IgG- or IgM- containing circulating immune complexes occurred in any of the challenged patients. No significant abnormalities of serum complement levels (C3, C4, factor B) were detected in any of the patients including those challenged with gluten. Sucrose density-gradient ultracentrifugation studies revealed that the IgA-containing circulating immune complexes had sedimentation characteristics between 9S and 13S. The presence of circulating immune complexes in only 59% of patients with GSE, their lack of correlation with disease activity, and their failure to change during dietary gluten challenge suggests that circulating immune complexes do not play a primary role in the pathogenesis of GSE. PMID:7318253

  2. Fecal Markers of Environmental Enteropathy and Subsequent Growth in Bangladeshi Children.

    PubMed

    Arndt, Michael B; Richardson, Barbra A; Ahmed, Tahmeed; Mahfuz, Mustafa; Haque, Rashidul; John-Stewart, Grace C; Denno, Donna M; Petri, William A; Kosek, Margaret; Walson, Judd L

    2016-09-01

    Environmental enteropathy (EE), a subclinical intestinal disorder characterized by mucosal inflammation, reduced barrier integrity, and malabsorption, appears to be associated with increased risk of stunting in children in low- and middle-income countries. Fecal biomarkers indicative of EE (neopterin [NEO], myeloperoxidase [MPO], and alpha-1-antitrypsin [AAT]) have been negatively associated with 6-month linear growth. Associations between fecal markers (NEO, MPO, and AAT) and short-term linear growth were examined in a birth cohort of 246 children in Bangladesh. Marker concentrations were categorized in stool samples based on their distribution (< first quartile, interquartile range, > third quartile), and a 10-point composite EE score was calculated. Piecewise linear mixed-effects models were used to examine the association between markers measured quarterly (in months 3-21, 3-9, and 12-21) and 3-month change in length-for-age z-score (ΔLAZ). Children with high MPO levels at quarterly time points lost significantly more LAZ per 3-month period during the second year of life than those with low MPO (ΔLAZ = -0.100; 95% confidence interval = -0.167 to -0.032). AAT and NEO were not associated with growth; however, composite EE score was negatively associated with subsequent 3-month growth. In this cohort of children from an urban setting in Bangladesh, elevated MPO levels, but not NEO or AAT levels, were associated with decreases in short-term linear growth during the second year of life, supporting previous data suggesting the relevance of MPO as a marker of EE. PMID:27352872

  3. Cell therapy for autoimmune diseases

    PubMed Central

    Dazzi, Francesco; van Laar, Jacob M; Cope, Andrew; Tyndall, Alan

    2007-01-01

    Cell therapy, pioneered for the treatment of malignancies in the form of bone marrow transplantation, has subsequently been tested and successfully employed in autoimmune diseases. Autologous haemopoietic stem cell transplantation (HSCT) has become a curative option for conditions with very poor prognosis such as severe forms of scleroderma, multiple sclerosis, and lupus, in which targeted therapies have little or no effect. The refinement of the conditioning regimens has virtually eliminated transplant-related mortality, thus making HSCT a relatively safe choice. Although HSCT remains a nonspecific approach, the knowledge gained in this field has led to the identification of new avenues. In fact, it has become evident that the therapeutic efficacy of HSCT cannot merely be the consequence of a high-dose immuno-suppression, but rather the result of a resetting of the abnormal immune regulation underlying autoimmune conditions. The identification of professional and nonprofessional immunosuppressive cells and their biological properties is generating a huge interest for their clinical exploitation. Regulatory T cells, found abnormal in several autoimmune diseases, have been proposed as central to achieve long-term remissions. Mesenchymal stem cells of bone marrow origin have more recently been shown not only to be able to differentiate into multiple tissues, but also to exert a potent antiproliferative effect that results in the inhibition of immune responses and prolonged survival of haemopoietic stem cells. All of these potential resources clearly need to be investigated at the preclinical level but support a great deal of enthusiasm for cell therapy of autoimmune diseases. PMID:17367542

  4. Diet, microbiota and autoimmune diseases.

    PubMed

    Vieira, S M; Pagovich, O E; Kriegel, M A

    2014-05-01

    There is growing evidence that the commensal bacteria in the gastrointestinal tract (the gut microbiota) influence the development of autoimmunity in rodent models. Since humans have co-evolved with commensals for millennia, it is likely that people, who are genetically predisposed to autoimmunity, harbor gut microbial communities that similarly influence the onset and/or severity of disease. Beyond the current efforts to identify such disease-promoting or -preventing commensals ("pathobionts" or "symbionts"), it will be important to determine what factors modulate them. Dietary changes are known to affect both the composition and function of the gut microbial communities, which in turn can alter the innate and adaptive immune system. In this review, we focus on the relationships between diet, microbiota, and autoimmune diseases. We hypothesize that the beneficial and life-prolonging effects of caloric restriction on a variety of autoimmune models including lupus might partly be mediated by its effects on the gut microbiome and associated virome, the collection of all viruses in the gut. We give recent examples of the immunomodulatory potential of select gut commensals and their products or diet-derived metabolites in murine models of arthritis, multiple sclerosis, and type 1 diabetes. Lastly, we summarize the published phenotypes of germ-free mouse models of lupus and speculate on any role of the diet-sensitive microbiome and virome in systemic lupus and the related antiphospholipid syndrome. PMID:24763536

  5. Cholestatic phenotypes of autoimmune hepatitis.

    PubMed

    Czaja, Albert J

    2014-09-01

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

  6. Rebooting autoimmunity with autologous HSCT.

    PubMed

    Snowden, John A

    2016-01-01

    Autologous hematopoietic stem cell transplantation (HSCT) is increasingly used for severe autoimmune and inflammatory diseases, but the mechanisms involved have yet to be elucidated. In this issue of Blood, Delemarre et al report their findings in both animal and human models which provide insights into restoration of functionality and diversity within the regulatory T-cell (Treg) compartment following HSCT. PMID:26744435

  7. Rethinking Mechanisms of Autoimmune Pathogenesis

    PubMed Central

    Pillai, Shiv

    2016-01-01

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

  8. Thyroid autoimmunity in pregnant Nigerians

    PubMed Central

    Kayode, Oluwatosin O.; Odeniyi, Ifedayo A.; Iwuala, Sandra; Olopade, Oluwarotimi B.; Fasanmade, Olufemi A.; Ohwovoriole, Augustine E.

    2015-01-01

    Context: Thyroid autoimmunity is a recognized disorder in pregnancy and is associated with a number of adverse pregnancy outcomes. Aim: This study set out to determine the relationship between pregnancy and thyroid autoimmunity in Nigerian women. Settings and Design: This was an analytical cross-sectional study carried out in a tertiary hospital in South Western Nigeria with a total study population of 108 pregnant and 52 nonpregnant women. Subjects and Methods: Serum thyroid stimulating hormone, free thyroxine and thyroid peroxidase antibodies (TPO-Ab) were quantitatively determined using enzyme linked immuno-assays. Pregnant women were grouped into three categories (<14 weeks, 14–28 weeks and > 28 weeks). The relationship between pregnancy and thyroid autoimmunity was determined using Spearman correlation. Analysis of variance was used in comparison of means, Chi-square test used in analyzing proportions while P ≤ 0.05 was considered as significant. Results: The mean age of the pregnant women was 30.4 ± 6.0 years while the mean gestational age of all pregnant women was 20.6 ± 9.6 weeks. The mean TPO-Ab of 11.58 IU/ml in the pregnant was significantly higher than that of the controls of 7.23 IU/ml (P < 0.001). Out of 108 pregnant women, 27 (25%) had elevated TPO-Ab as against about 2% of the nonpregnant women levels P < 0.001. The number of pregnant women with elevated TPO-Ab levels decreased from 33.3% in the first group to 25.6% and 15.2% in the second and third groups. Conclusion: Thyroid autoimmunity expressed by the presence of TPO-Ab is high among pregnant Nigerian women and the frequency of autoimmunity appears to decline with advancing gestational age. PMID:26425470

  9. Sex bias in paediatric autoimmune disease - Not just about sex hormones?

    PubMed

    Chiaroni-Clarke, Rachel C; Munro, Jane E; Ellis, Justine A

    2016-05-01

    Autoimmune diseases affect up to 10% of the world's population, and approximately 80% of those affected are female. The majority of autoimmune diseases occur more commonly in females, although some are more frequent in males, while others show no bias by sex. The mechanisms leading to sex biased disease prevalence are not well understood. However, for adult-onset autoimmune disease, at least some of the cause is usually ascribed to sex hormones. This is because levels of sex hormones are one of the most obvious physiological differences between adult males and females, and their impact on immune system function is well recognised. While for paediatric-onset autoimmune diseases a sex bias is not as common, there are several such diseases for which one sex predominates. For example, the oligoarticular subtype of juvenile idiopathic arthritis (JIA) occurs in approximately three times more girls than boys, with a peak age of onset well before the onset of puberty, and at a time when levels of androgen and oestrogen are low and not strikingly different between the sexes. Here, we review potential explanations for autoimmune disease sex bias with a particular focus on paediatric autoimmune disease, and biological mechanisms outside of sex hormone differences. PMID:26970680

  10. Functional characterization of IgA-targeted bacterial taxa from malnourished Malawian children that produce diet-dependent enteropathy

    PubMed Central

    Kau, Andrew L.; Planer, Joseph D.; Liu, Jie; Rao, Sindhuja; Yatsunenko, Tanya; Trehan, Indi; Manary, Mark J.; Liu, Ta-Chiang; Stappenbeck, Thaddeus S.; Maleta, Kenneth M.; Ashorn, Per; Dewey, Kathryn G.; Houpt, Eric R.; Hsieh, Chyi-Song; Gordon, Jeffrey I.

    2015-01-01

    To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mucosal immune/barrier function, we purified bacterial strains targeted by IgA from the fecal microbiota of two cohorts of Malawian infants and children. IgA responses to several bacterial taxa, including Enterobacteriaceae, correlated with anthropometric measurements of nutritional status in longitudinal studies. The relationship between IgA responses and growth was further explained by enteropathogen burden. Gnotobiotic mouse recipients of an IgA+-bacterial consortium purified from the gut microbiota of undernourished children exhibited a diet-dependent enteropathy characterized by rapid disruption of the small intestinal and colonic epithelial barrier, weight loss and sepsis that could be prevented by administering two IgA-targeted bacterial species from a healthy microbiota. Dissection of a culture collection of 11 IgA-targeted strains from an undernourished donor, sufficient to transmit these phenotypes, disclosed that Enterobacteriaceae interacted with other consortium members to produce enteropathy. These findings indicate that bacterial targets of IgA responses have etiologic, diagnostic, and therapeutic implications for childhood undernutrition. PMID:25717097

  11. Metronidazole reduces intestinal inflammation and blood loss in non-steroidal anti-inflammatory drug induced enteropathy.

    PubMed Central

    Bjarnason, I; Hayllar, J; Smethurst, P; Price, A; Gumpel, M J

    1992-01-01

    This study assessed the effect of metronidazole on the gastroduodenal mucosa, intestinal permeability, blood loss, and inflammation in patients on non-steroidal anti-inflammatory drugs (NSAIDs). Thirteen patients were studied before and after 2-12 weeks' treatment with metronidazole 800 mg/day, while maintaining an unchanged NSAID intake. Intestinal inflammation, as assessed by the faecal excretion of indium-111 labelled neutrophils, and blood loss, assessed with chromium-51 labelled red cells, were significantly reduced after treatment (mean (SD) 111In excretion 4.7 (4.7)% v 1.5 (1.3)% (N < 1.0%), p < 0.001, 51Cr red cells loss 2.6 (1.6) ml/day v 0.9 (0.5) ml/day (N < 1.0 ml/day), p < 0.01). Intestinal permeability assessed as the 5 hour urinary excretion ratio of 51CrEDTA/L-rhamnose did not change significantly (0.133 (0.046) v 0.154 (0.064), p > 0.1) and there were no significant changes in the endoscopic or microscopic appearances of the gastroduodenal mucosa. These results suggest that the neutrophil is the main damaging effector cell in NSAID induced enteropathy. The main neutrophil chemo-attractant in this enteropathy may be a metronidazole sensitive microbe. PMID:1427372

  12. High dose intravenous immunoglobulin in autoimmune rheumatic disorders.

    PubMed

    Zeuner, R A; Euler, H H; Schroeder, J O

    1997-11-01

    Since the effectiveness of high dose intravenous immunoglobulin (IVIg) was first demonstrated in autoimmune thrombocytopenia, IVIg has been investigated in the treatment of various autoimmune rheumatic disorders. Controlled randomised studies have established the efficacy of IVIg in Kawasaki's syndrome, for which combined IVIg and aspirin (acetylsalicylic acid) now constitutes the standard treatment. Another controlled study has demonstrated the benefit of IVIg in dermatomyositis. IVIg treatment in juvenile rheumatoid arthritis has produced contradictory results. Uncontrolled studies and case reports on the application of IVIg in systemic lupus erythematosus, ANCA-associated vasculitides and adult rheumatoid arthritis generally describe short term positive effects. Various mechanisms are thought to underlie the effect of IVIg on autoimmune rheumatic diseases, such as: blockade of Fc receptors;immunomodulation via anti-idiotypic interactions;inhibition of complement-mediated tissue damage;modulation of cytokine expression by leucocytes and endothelial cells; andinhibition of superantigen-mediated T cell activation. IVIg is considered to be a low-risk form of treatment. Reported adverse effects include headache, aseptic meningitis and transient impairment of renal function. Haemolysis and anaphylactic reactions are rare. The effect profile of IVIg makes it a relevant, although still experimental, form of treatment in autoimmune rheumatic disorders, but its high cost renders it unsuitable as a first-line treatment. Because IVIg does not weaken patients' resistance to infection, it might serve as a therapeutic option in bridging clinical situations where immunosuppressive or cytotoxic approaches are contraindicated in patients with autoimmune disorders, such as intercurrent infection or in the period immediately before and after surgery. PMID:18020527

  13. MicroRNA in autoimmunity and autoimmune diseases

    PubMed Central

    Pauley, Kaleb M.; Cha, Seunghee; Chan, Edward K.L.

    2009-01-01

    MicroRNAs (miRNAs) are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3′ untranslated region (UTR) of specific messenger RNAs (mRNAs) for degradation or translational repression. miRNA-mediated gene regulation is critical for normal cellular functions such as the cell cycle, differentiation, and apoptosis, and as much as one-third of human mRNAs may be miRNA targets. Emerging evidence has demonstrated that miRNAs play a vital role in the regulation of immunological functions and the prevention of autoimmunity. Here we review the many newly discovered roles of miRNA regulation in immune functions and in the development of autoimmunity and autoimmune disease. Specifically, we discuss the involvement of miRNA regulation in innate and adaptive immune responses, immune cell development, T regulatory cell stability and function, and differential miRNA expression in rheumatoid arthritis and systemic lupus erythematosus. PMID:19303254

  14. Multiple micronutrient supplementation transiently ameliorates environmental enteropathy in Malawian children aged 12-35 months in a randomized controlled clinical trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Environmental enteropathy (EE) is subclinical, diffuse villous atrophy characterized by T cell infiltration of the small intestinal mucosa associated with nutrient malabsorption and stunting. EE is assessed by the lactulose:mannitol (L:M) test, whereby nonmetabolized sugars are ingested and quantifi...

  15. sirt1-null mice develop an autoimmune-like condition

    SciTech Connect

    Sequeira, Jedon; Boily, Gino; Bazinet, Stephanie; Saliba, Sarah; He Xiaohong; Jardine, Karen; Kennedy, Christopher; Staines, William; Rousseaux, Colin; Mueller, Rudi; McBurney, Michael W.

    2008-10-01

    The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease.

  16. Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan.

    PubMed

    Tomita, Sakura; Kikuti, Yara Y; Carreras, Joaquim; Kojima, Minoru; Ando, Kiyoshi; Takasaki, Hirotaka; Sakai, Rika; Takata, Katsuyoshi; Yoshino, Tadashi; Bea, Silvia; Campo, Elias; Nakamura, Naoya

    2015-10-01

    Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs de novo and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence in situ hybridization (FISH) at five different loci: 1q21.3 (CKS1B), 6q16.3 (HACE1), 7p22.3 (MAFK), 9q33.3 (PPP6C), and 9q34.3 (ASS1, CARD9) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium- to large-sized cells in 13 cases (65%), small- to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2(+) (60%), CD3ɛ(+) (100%), CD4(+) (10%), CD7(+) (95%), CD8(+) (80%), CD56(+) (85%), TIA-1(+) (100%), Granzyme B(+) (25%), T-cell receptor (TCR)β(+) (10%), TCRγ(+) (35%), TCRγδ(+) (50%), and double negative for TCR (six cases, 30%). All cases were EBER(-). The genomic profile showed recurrent copy number gains of 1q32.3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8(+) CD56(+) phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including MYC). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of αβ-T-cells and γδ-T-cells. PMID

  17. Impact of mass screening for gluten-sensitive enteropathy in working population

    PubMed Central

    Mariné, Meritxell; Fernández-Bañares, Fernando; Alsina, Montserrat; Farré, Carme; Cortijo, Montserrat; Santaolalla, Rebeca; Salas, Antonio; Tomàs, Margarita; Abugattas, Elias; Loras, Carme; Ordás, Ingrid; Viver, Josep M; Esteve, Maria

    2009-01-01

    AIM: To assess: (1) frequency and clinical relevance of gluten sensitive enteropathy (GSE) detected by serology in a mass screening program; (2) sensitivity of antitransglutaminase (tTGA) and antiendomysium antibodies (EmA); and (3) adherence to gluten-free diet (GFD) and follow-up. METHODS: One thousand, eight hundred and sixty-eight subjects recruited from an occupational health department underwent analysis for tTGA and EmA and, if positive, duodenal biopsy, DQ2/DQ8 genotyping, clinical feature recording, blood tests, and densitometry were performed. Since > 98% of individuals had tTGA < 2 U/mL, this value was established as the cut-off limit of normality and was considered positive when confirmed twice in the same sample. Adherence to a GFD and follow up were registered. RESULTS: Twenty-six (1.39%) subjects had positive tTGA and/or EmA, and 21 underwent biopsy: six Marsh III (one IIIa, four IIIb, one IIIc), nine Marsh I and six Marsh 0 (frequency of GSE 1:125). The sensitivity of EmA for GSE was 46.6% (11.1% for Marsh I, 100% for Marsh III), while for tTGA, it was 93.3% (88.8% for Marsh I, 100% for Marsh III). All 15 patients with abnormal histology had clinical features related to GSE. Marsh I and III subjects had more abdominal pain than Marsh 0 (P = 0.029), and a similar trend was observed for distension and diarrhea. No differences in the percentage of osteopenia were found between Marsh I and III (P = 0.608). Adherence to follow-up was 69.2%. Of 15 GSE patients, 66.7% followed a GFD with 80% responding to it. CONCLUSION: GSE in the general population is frequent and clinically relevant, irrespective of histological severity. tTGA is the marker of choice. Mass screening programs are useful in identifying patients who can benefit from GFD and follow-up. PMID:19294762

  18. Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh

    PubMed Central

    Naylor, Caitlin; Lu, Miao; Haque, Rashidul; Mondal, Dinesh; Buonomo, Erica; Nayak, Uma; Mychaleckyj, Josyf C.; Kirkpatrick, Beth; Colgate, Ross; Carmolli, Marya; Dickson, Dorothy; van der Klis, Fiona; Weldon, William; Steven Oberste, M.; Ma, Jennie Z.; Petri, William A.

    2015-01-01

    Background Environmental enteropathy (EE) is a subclinical enteric condition found in low-income countries that is characterized by intestinal inflammation, reduced intestinal absorption, and gut barrier dysfunction. We aimed to assess if EE impairs the success of oral polio and rotavirus vaccines in infants in Bangladesh. Methods We conducted a prospective observational study of 700 infants from an urban slum of Dhaka, Bangladesh from May 2011 to November 2014. Infants were enrolled in the first week of life and followed to age one year through biweekly home visits with EPI vaccines administered and growth monitored. EE was operationally defied as enteric inflammation measured by any one of the fecal biomarkers reg1B, alpha-1-antitrypsin, MPO, calprotectin, or neopterin. Oral polio vaccine success was evaluated by immunogenicity, and rotavirus vaccine response was evaluated by immunogenicity and protection from disease. This study is registered with ClinicalTrials.gov, number NCT01375647. Findings EE was present in greater than 80% of infants by 12 weeks of age. Oral poliovirus and rotavirus vaccines failed in 20.2% and 68.5% of the infants respectively, and 28.6% were malnourished (HAZ < − 2) at one year of age. In contrast, 0%, 9.0%, 7.9% and 3.8% of infants lacked protective levels of antibody from tetanus, Haemophilus influenzae type b, diphtheria and measles vaccines respectively. EE was negatively associated with oral polio and rotavirus response but not parenteral vaccine immunogenicity. Biomarkers of systemic inflammation and measures of maternal health were additionally predictive of both oral vaccine failure and malnutrition. The selected biomarkers from multivariable analysis accounted for 46.3% variation in delta HAZ. 24% of Rotarix® IgA positive individuals can be attributed to the selected biomarkers. Interpretation EE as well as systemic inflammation and poor maternal health were associated with oral but not parenteral vaccine

  19. Animal Models of Autoimmune Neuropathy

    PubMed Central

    Soliven, Betty

    2014-01-01

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

  20. Propylthiouracil-induced autoimmune disease

    PubMed Central

    Paiaulla, Santosh; Venkategowda, Pradeep Marur; Rao, S. Manimala; Balaraju, Banda

    2015-01-01

    Hyperthyroidism is a condition characterized by excessive production of thyroid hormones. Propylthiouracil (PTU) is commonly used as first line drug in the management of hyperthyroidism. This is a case report of 24-year-old female, a known case of hyperthyroidism since 4 years, who came with a history of fever and myalgia since 3 days and dyspnea with coughing out of blood since 1 day. Patient was taking PTU (100 mg per day) since 4 years for hyperthyroidism. Patient was immediately intubated for type-II respiratory failure. Diagnosed to be having PTU-induced autoimmune disease. PTU was stopped and treated with methylprednisolone and cyclophosphamide. Clinical features improved over a period of 8 days and discharged home successfully. Having a high suspicion for the onset of autoimmune disease in hyperthyroidism patients who are on PTU therapy and timely treatment with immunosuppressants and supportive care along with the withdrawal of the drug can make a difference in morbidity and mortality. PMID:26321810

  1. Progranulin antibodies in autoimmune diseases.

    PubMed

    Thurner, Lorenz; Preuss, Klaus-Dieter; Fadle, Natalie; Regitz, Evi; Klemm, Philipp; Zaks, Marina; Kemele, Maria; Hasenfus, Andrea; Csernok, Elena; Gross, Wolfgang L; Pasquali, Jean-Louis; Martin, Thierry; Bohle, Rainer Maria; Pfreundschuh, Michael

    2013-05-01

    Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. PMID:23149338

  2. Expression of serotonin, chromogranin-A, serotonin receptor-2B, tryptophan hydroxylase-1, and serotonin reuptake transporter in the intestine of dogs with chronic enteropathy.

    PubMed

    Bailey, Candice; Ruaux, Craig; Stang, Bernadette V; Valentine, Beth A

    2016-05-01

    Serotonin regulates many intestinal motor and sensory functions. Altered serotonergic metabolism has been described in human gastrointestinal diseases. The objective of our study was to compare expression of several components of the serotonergic system [serotonin (5-HT), serotonin reuptake transporter protein (SERT), tryptophan hydroxylase-1 (TPH-1), 5-HT receptor2B (5-HT2B)] and the enterochromaffin cell marker chromogranin-A (CgA) in the intestinal mucosa between dogs with chronic enteropathy and healthy controls. Serotonin and CgA expression were determined by immunohistochemistry using banked and prospectively obtained, paraffin-embedded canine gastrointestinal biopsies (n = 11), and compared to a control group of canine small intestinal sections (n = 10). Expression of SERT, TPH-1, and 5-HT2B were determined via real-time reverse transcription (qRT)-PCR using prospectively collected endoscopic duodenal biopsies (n = 10) and compared to an additional control group of control duodenal biopsies (n = 8, control group 2) showing no evidence of intestinal inflammation. Dogs with chronic enteropathies showed strong staining for both 5-HT and CgA. Mean positive cells per high power field (HPF) were significantly increased for both compounds in dogs with chronic enteropathies (p < 0.001 for 5-HT; p < 0.05 for CgA). The number of 5-HT-positive and CgA-positive cells/HPF showed significant correlation in the entire group of dogs, including both diseased and healthy individuals (Pearson r(2) = 0.2433, p = 0.016). No significant differences were observed for SERT, TPH-1, or 5-HT2B expression; however, dogs with chronic enteropathy showed greater variability in expression of TPH-1 and 5-HT2B We conclude that components of the neuroendocrine system show altered expression in the intestinal mucosa of dogs with chronic enteropathy. These changes may contribute to nociception and clinical signs in these patients. PMID:27026108

  3. [Autoimmune hepatitis induced by isotretionine].

    PubMed

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

    2016-01-01

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

  4. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    PubMed Central

    Saif, Muhammad Wasif

    2014-01-01

    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

  5. Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy

    PubMed Central

    Asmuth, David M.; Ma, Zhong-Min; Albanese, Anthony; Sandler, Netanya G.; Devaraj, Sridevi; Knight, Thomas H.; Flynn, Neil M.; Yotter, Tammy; Garcia, Juan-Carlos; Tsuchida, Emily; Wu, Tsung-Teh; Douek, Daniel C.; Miller, Christopher J.

    2013-01-01

    Objectives: To examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy. Design: Open-label trial with intensive 8-week phase of bovine serum immunoglobulin (SBI) 2.5 g twice daily with a 4-week washout period and an optional 9-month extension study. Methods: HIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastrointestinal questionnaire assessed changes in symptoms. Results: All eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P = 0.008) and improvements in stool consistency (P = 0.008). Gut permeability was normal before and after the intervention, but d-xylose absorption increased in seven of eight participants. Mucosal CD4+ lymphocyte densities increased by a median of 139.5 cells/mm2 from 213 to 322 cells/mm2 (P = 0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P = 0.039), and then fell below baseline in four of five who continued receiving SBI (P = 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4+ lymphocyte densities (r = −0.74, P = 0.046). Conclusion: SBI significantly increases intestinal mucosal CD4+ lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting

  6. Autoimmunity in primary T-cell immunodeficiencies.

    PubMed

    Azizi, Gholamreza; Ghanavatinejad, Alireza; Abolhassani, Hassan; Yazdani, Reza; Rezaei, Nima; Mirshafiey, Abbas; Aghamohammadi, Asghar

    2016-09-01

    Primary immunodeficiency diseases (PID) are a genetically heterogeneous group of more than 270 disorders that affect distinct components of both humoral and cellular arms of the immune system. Primary T cell immunodeficiencies affect subjects at the early age of life. In most cases, T-cell PIDs become apparent as combined T- and B-cell deficiencies. Patients with T-cell PID are prone to life-threatening infections. On the other hand, non-infectious complications such as lymphoproliferative diseases, cancers and autoimmunity seem to be associated with the primary T-cell immunodeficiencies. Autoimmune disorders of all kinds (organ specific or systemic ones) could be subjected to this class of PIDs; however, the most frequent autoimmune disorders are immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). In this review, we discuss the proposed mechanisms of autoimmunity and review the literature reported on autoimmune disorder in each type of primary T-cell immunodeficiencies. PMID:27063703

  7. Eosinophil-Rich Acute Febrile Neutrophilic Dermatosis in a Patient With Enteropathy-Associated T-cell Lymphoma, Type 1.

    PubMed

    Soon, Christopher W; Kirsch, Ilan R; Connolly, Andrew J; Kwong, Bernice Y; Kim, Jinah

    2016-09-01

    The presence of eosinophils within the neutrophilic infiltrates of acute febrile neutrophilic dermatosis (Sweet syndrome) is documented in the literature. Here, the authors describe a case of eosinophil-rich acute febrile neutrophilic dermatosis in the setting of new onset enteropathy-associated T-cell lymphoma (EATL), type 1. Histopathologic evaluation of the skin biopsies demonstrated a mixed superficial perivascular and inflammatory infiltrate composed of neutrophils, lymphocytes, and abundant eosinophils. EATL, type 1 is an aggressive although rare primary intestinal lymphoma that may be associated with celiac disease. This lymphoma is associated with a poor prognosis due to treatment resistance or bowel perforation. To the authors' knowledge, Sweet syndrome has not been reported in a patient with EATL. PMID:27097333

  8. Hemophagocytic Lymphohistiocytic Syndrome and Enteropathy-Associated T-cell Lymphoma in a Patient with Refractory Celiac Disease.

    PubMed

    Lu, Lucy; Ning, Shuoyan; Kassam, Zain; Hunt, Richard; Puglia, Marco

    2014-04-01

    A 70-year-old woman with celiac disease presented with weight loss and diarrhea unresponsive to gluten-free diet (GFD) and prednisone. Diagnosis of type 2 refractory celiac disease (RCD) was made by small intestinal biopsies showing severe villous blunting and intraepithelial lymphocytosis. She was diagnosed with hemophagocytic lymphohistiocytic syndrome (HLH) after developing fever, pancytopenia, hypofibrinogenemia, elevated ferritin, and demonstration of hemophagocytosis on her bone marrow biopsy. An expert pathologist on lymphoma reviewed her biopsies and revised the final diagnosis to type 1 enteropathy-associated T-cell lymphoma (EATL) based on large T-cells infiltrating the lamina propria. We describe the first case of HLH associated with localized EATL and RCD. PMID:26157854

  9. Further investigation of exposure to Lawsonia intracellularis in wild and feral animals captured on horse properties with equine proliferative enteropathy.

    PubMed

    Pusterla, Nicola; Mapes, Samantha; Gebhart, Connie

    2012-11-01

    This study investigated the exposure to Lawsonia intracellularis in wild birds, mice, rabbits, raccoons, coyotes and squirrels, and feral cats and pigs on 10 farms with confirmed equine proliferative enteropathy (EPE). Serum samples from all resident foals (417 samples) as well as fecal (461) and serum (106) samples from wild and feral animals were collected for serological and molecular detection of L. intracellularis following the diagnosis of EPE in index cases. A total of three cats from two farms, three mice from two farms and eight cottontail rabbits from one farm had evidence of prior exposure to L. intracellularis. These animals may be an indicator of environmental exposure or may be actively involved in the transmission of L. intracellularis to foals by acting as a potential reservoir/amplifier host. PMID:22627048

  10. Antimicrobial susceptibility testing of two Lawsonia intracellularis isolates associated with proliferative hemorrhagic enteropathy and porcine intestinal adenomatosis in South Korea.

    PubMed

    Yeh, Jung-Yong; Lee, Ji-Hye; Yeh, Hye-Ryun; Kim, Aeran; Lee, Ji Youn; Hwang, Jeong-Min; Kang, Bo-Kyu; Kim, Jong-Man; Choi, In-Soo; Lee, Joong-Bok

    2011-09-01

    This study represents the first published data on antimicrobial susceptibility of Asian isolates of Lawsonia intracellularis. We assessed MICs of 16 antimicrobials for two isolates of L. intracellularis recovered from diseased pigs in South Korea, one from a finisher pig with acute proliferative hemorrhagic enteropathy in 2002 and the other from a grower pig with porcine intestinal adenomatosis in 2010. Tylosin and tilmicosin were found to be the most active against L. intracellularis both intracellularly (MICs, 0.25 to 0.5 μg/ml and 0.125 μg/ml, respectively) and extracellularly (MICs, 0.25 to 0.5 μg/ml and 1 μg/ml, respectively). PMID:21690283

  11. Treatment challenges and investigational opportunities in autoimmune hepatitis.

    PubMed

    Czaja, Albert J; Bianchi, Francesco B; Carpenter, Herschel A; Krawitt, Edward L; Lohse, Ansgar W; Manns, Michael P; McFarlane, Ian G; Mieli-Vergani, Giorgina; Toda, Gotaro; Vergani, Diego; Vierling, John; Zeniya, Mikio

    2005-01-01

    New drugs and advances in molecular biology afford opportunities to upgrade the treatment of autoimmune hepatitis. The aims of this study were to define treatment problems, identify possible solutions, and stimulate investigations to improve patient care. A clinical subcommittee of the International Autoimmune Hepatitis Group reviewed current management difficulties and proposed corrective actions. The assessment of new front-line and salvage therapies for adults and children were given top priority. Cyclosporine and mycophenolate mofetil were endorsed as drugs worthy of rigorous study in severe disease, and budesonide was endorsed for study as front-line therapy in mild disease. Diagnostic criteria and treatment regimens for children required codification, and pharmacokinetic studies were encouraged to develop optimal dosing schedules based on therapeutic ranges. Collaborative efforts were proposed to help understand racial, geographical, and genetic factors affecting outcome and to establish definitions and therapies for variant syndromes and graft dysfunction after transplantation. The development of experimental animal models was deemed essential for the study of site-specific molecular interventions, and gene therapy was endorsed as a means of bolstering reparative processes. In conclusion, evolving pharmacological and technical advances promise to improve the treatment of autoimmune hepatitis, and investigations of these advances are timely, feasible, and necessary. PMID:15690485

  12. Autoimmune thrombocytopenia (AITP) and thyroid autoimmune disease (TAD): overlapping syndromes?

    PubMed Central

    Cordiano, I; Betterle, C; Spadaccino, C A; Soini, B; Girolami, A; Fabris, F

    1998-01-01

    The pathogenesis of thrombocytopenia associated with TAD and the occurrence of overlapping traits between TAD and AITP are still a matter of debate. For this reason, we investigated for the presence and specificity of platelet and thyroid autoantibodies in 18 TAD patients with thrombocytopenia, 19 TAD patients without thrombocytopenia and in 22 patients with primary AITP without clinical signs of TAD. Platelet-associated IgG and/or specific circulating platelet autoantibodies were detected in 83% of patients with TAD and thrombocytopenia, in 10% of patients with TAD without thrombocytopenia and in 86% of patients with primary AITP. The reactivity of serum autoantibodies, assayed by MoAb immobilization of platelet antigens (MAIPA), was directed against platelet glycoproteins Ib and/or IIb/IIIa in 50% of the patients with TAD and thrombocytopenia, as in 46% of the patients with primary AITP. Thyroid autoantibodies were found in 89% of patients with TAD and thrombocytopenia, in 95% of patients with TAD without thrombocytopenia, and in 18% of patients with primary AITP. Thyrotropin (TSH) levels determined in three of four AITP patients with thyroid autoantibodies revealed a subclinical hyperthyroidism in one patient. The present study supports the autoimmune aetiology of thrombocytopenia associated with TAD, since the prevalence and specificity of platelet autoantibodies are similar in TAD and primary AITP. The results indicate also that there exists an overlap between thyroid and platelet autoimmunity with or without clinical manifestations. PMID:9737665

  13. Anatabine ameliorates experimental autoimmune thyroiditis.

    PubMed

    Caturegli, Patrizio; De Remigis, Alessandra; Ferlito, Marcella; Landek-Salgado, Melissa A; Iwama, Shintaro; Tzou, Shey-Cherng; Ladenson, Paul W

    2012-09-01

    Tobacco smoking favorably influences the course of Hashimoto thyroiditis, possibly through the antiinflammatory proprieties of nicotine. In this study we tested anatabine, another tobacco alkaloid, in a model of experimental autoimmune thyroiditis. Experimental autoimmune thyroiditis was induced by different doses of thyroglobulin, to produce a disease of low, moderate, or high severity, in 88 CBA/J female mice: 43 drank anatabine supplemented water and 45 regular water. Mice were bled after immunization and killed to assess thyroid histopathology, thyroglobulin antibodies, T(4), and thyroid RNA expression of 84 inflammatory genes. We also stimulated in vitro a macrophage cell line with interferon-γ or lipopolysaccharide plus or minus anatabine to quantitate inducible nitric oxide synthase and cyclooxygenase 2 protein expression. Anatabine reduced the incidence and severity of thyroiditis in the moderate disease category: only 13 of 21 mice (62%) developed thyroid infiltrates when drinking anatabine as compared with 22 of 23 (96%) controls (relative risk 0.59, P = 0.0174). The median thyroiditis severity was 0.5 and 2.0 in anatabine and controls, respectively (P = 0.0007 by Wilcoxon rank sum test). Anatabine also reduced the antibody response to thyroglobulin on d 14 (P = 0.029) and d 21 (P = 0.045) after immunization and improved the recovery of thyroid function on d 21 (P = 0.049). In the thyroid transcriptome, anatabine restored expression of IL-18 and IL-1 receptor type 2 to preimmunization levels. Finally, anatabine suppressed in a dose-dependent manner macrophage production of inducible nitric oxide synthase and cyclooxygenase 2. Anatabine ameliorates disease in a model of autoimmune thyroiditis, making the delineation of its mechanisms of action and potential clinical utility worthwhile. PMID:22807490

  14. Thymoma with Autoimmune Hemolytic Anemia

    PubMed Central

    Suzuki, Kensuke; Inomata, Minehiko; Shiraishi, Shiori; Hayashi, Ryuji; Tobe, Kazuyuki

    2014-01-01

    A 38-year-old Japanese male was referred to our hospital with abnormal chest X-ray results and severe Coombs-positive hemolytic anemia. He was diagnosed with a stage IV, WHO type A thymoma and was treated with oral prednisolone (1 mg/kg/day) and subsequent chemotherapy. After chemotherapy, the patient underwent surgical resection of the thymoma. Hemolysis rapidly disappeared and did not return after the discontinuation of oral corticosteroids. Corticosteroid therapy may be preferable to chemotherapy or thymoma surgical resection in the management of autoimmune hemolytic anemia with thymoma. PMID:25722666

  15. The Immunogenetics of Autoimmune Cholestasis.

    PubMed

    Trivedi, Palak J; Hirschfield, Gideon M

    2016-02-01

    The immune-mediated hepatobiliary diseases, primary biliary cirrhosis and primary sclerosing cholangitis are relatively rare, albeit and account for a significant amount of liver transplant activity and liver-related mortality globally. Precise disease mechanisms are yet to be described although a contributory role of genetic predisposition is firmly established. In addition to links with the major histocompatibility complex, a number of associations outside this region harbor additional loci which underscore the fundamental role of breaks in immune tolerance and mucosal immunogenicity in the pathogenesis of autoimmune biliary disease. We provide an overview of these key discoveries before discussing putative avenues of therapeutic exploitation based on existing findings. PMID:26593288

  16. Immunomodulatory vaccines against autoimmune diseases.

    PubMed

    Sela, Michael

    2006-01-01

    Vaccines are for healthy people, to prevent them from becoming ill. Such prophylactic vaccines have been a great success. Therapeutic vaccines become more and more important, especially as life expectancy increases. Efforts to develop vaccines against such diseases as cancer, AIDS, hepatitis, tuberculosis, Alzheimer disease, and mad cow disease have not yet reached the stage where they can be successfully used on a daily basis. However, significant progress has been made in the realm of autoimmune diseases, resulting (at least in one case) in an immunomodulatory vaccine against multiple sclerosis that was developed in the author's laboratory, and that is in daily use by about 100,000 patients. The drug or therapeutic vaccine against the exacerbating-remitting type of multiple sclerosis is a copolymer of four amino acid residues, denoted Copaxone, which are related to myelin basic protein. This paper discusses Copaxone as well as a candidate immunomodulatory vaccine against myasthenia gravis, a peptide derived from the nicotinic acetylcholine receptor. Copolymer 1 (Cop 1, glatiramer acetate, Copaxone) is a synthetic amino acid random copolymer that is immunologically cross-reactive with myelin basic protein and suppresses experimental allergic encephalomyelitis in several animal species. Cop 1 slows the progression of disability and reduces the relapse rate in exacerbating-remitting multiple sclerosis patients. Cop 1 is a potent inducer of T helper 2 (Th2) regulatory cells in mice and humans; and Th2 cells are found in both the brains and spinal cords of Cop 1-treated mice and humans. MG and experimental autoimmune MG are T cell-regulated, antibody-mediated autoimmune diseases. Two peptides, representing sequences of the human AChR-alpha-subunit, p195-212 and p259-271, are immunodominant T-cell epitopes in MG patients and two strains of mice. Altered peptide ligand, composed of the randomly arranged two single amino acid analogs inhibits in vitro and in vivo MG

  17. Therapy of autoimmune bullous diseases

    PubMed Central

    Mutasim, Diya F

    2007-01-01

    Autoimmune bullous diseases result from an immune response to molecular components of the desmosome or basement membrane. Bullous diseases are associated with a high degree of morbidity and occasional mortality. Therapy of bullous diseases consists of suppressing the immune system, controlling inflammation and improving healing of erosions. The therapeutic agents used in the treatment of bullous diseases may be associated with high morbidity and occasional mortality. Successful treatment requires understanding of the pathophysiology of the disease process and the pharmacology of the drugs being used. PMID:18360613

  18. Autoimmune Cytopenias In Common Variable Immunodeficiency

    PubMed Central

    Podjasek, Jenna C.; Abraham, Roshini S.

    2012-01-01

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

  19. Autoimmune cytopenias in common variable immunodeficiency.

    PubMed

    Podjasek, Jenna C; Abraham, Roshini S

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  1. Developmental expression of autoimmune target antigens during organogenesis.

    PubMed Central

    Akashi, T; Eishi, Y

    1991-01-01

    A common factor existing among autoimmune target antigens was sought in association with their developmental expression during organogenesis. Autoimmunity against a certain organ was experimentally induced in rats by deliberate immunization with whole tissue extract of the respective organ. Histopathological changes in a target organ of the immunized rats were recorded, and tissue specificity of the raised autoantibodies was immunohistologically examined with tissue sections of normal adult rats. These immune sera were also reacted with tissue sections of a target organ in each stage of organogenesis, and the time of first expression of the target antigen was determined for each immune serum. As a result, induced autoantibodies were directed only to a limited number of tissue antigens, such as thyroid follicular antigens [gestation day 17 (17 GD)], salivary ductal antigens (18 GD), anterior pituitary antigens (21 GD), gastric parietal cell antigens (22 GD), neural myelin antigens (2 days after birth), retinal photo-receptor cell antigens (3 days after birth) and testicular germ cell antigens (4 weeks after birth). They were first expressed on the day indicated in parentheses. Comparing with the development of the immune system, which was monitored by demonstrating CD4- and/or CD8-positive cells in the developing thymus and spleen, a common feature of these potential autoimmune target antigens was found to be that they were expressed either in parallel with, or after, but never before, the development of the immune system. This observation might suggest why only a limited number of self antigens can be autoimmune target antigens among the enormously large number of antigen determinants existing in the whole extract of each organ. Images Figure 1 Figure 2 Figure 3 PMID:1769700

  2. Cystic Lesions in Autoimmune Pancreatitis.

    PubMed

    Gompertz, Macarena; Morales, Claudia; Aldana, Hernán; Castillo, Jaime; Berger, Zoltán

    2015-01-01

    Autoimmune pancreatitis (AIP) can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases. PMID:26675058

  3. Cardiovascular Involvement in Autoimmune Diseases

    PubMed Central

    Amaya-Amaya, Jenny

    2014-01-01

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

  4. Susceptibility Genes in Thyroid Autoimmunity

    PubMed Central

    Ban, Yoshiyuki; Tomer, Yaron

    2005-01-01

    The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine) is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT) and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg). Most likely, these loci interact and their interactions may influence disease phenotype and severity. PMID:15712599

  5. Defining and analyzing geoepidemiology and human autoimmunity.

    PubMed

    Shapira, Yinon; Agmon-Levin, Nancy; Shoenfeld, Yehuda

    2010-05-01

    Autoimmune diseases cumulatively affect 5-10% of the industrial world population and are a significant cause of morbidity and mortality. In recent decades rates are rising worldwide, and autoimmunity can no longer be associated solely with the more developed "Western" countries. Geoepidemiology of autoimmune diseases portrays the burden of these illnesses across various regions and ethnic populations. Furthermore, Geoepidemiology may yield important clues to the genetic and triggering environmental mechanisms of autoimmunity. In this review we compiled and discuss in depth abundant geoepidemiological data pertaining to four major autoimmune conditions, namely type-1 diabetes mellitus, multiple sclerosis, autoimmune thyroid disease, and inflammatory bowel disease. The following key results manifested in this review: 1) Ethno-geographic gradients in autoimmune disease risk are attributable to a complex interplay of genetic and environmental pressures. 2) Industrial regions, particularly Northern Europe and North America, still exhibit the highest rates for most autoimmune diseases. 3) Methods particularly useful in demonstrating the significant influence of genetic and environmental factors include comparative ethnic differences studies, migration studies, and recognition of 'hotspots'. 4) Key environmental determinants of geographical differences include diminished ultraviolet radiation exposure, Western or affluence-related lifestyle, infection exposure, environmental pollutants, nutritional factors and disease-specific precipitants (e.g., iodine exposure). PMID:20034761

  6. Helicobacter pylori and skin autoimmune diseases.

    PubMed

    Magen, Eli; Delgado, Jorge-Shmuel

    2014-02-14

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

  7. Sex bias in CNS autoimmune disease mediated by androgen control of autoimmune regulator.

    PubMed

    Zhu, Meng-Lei; Bakhru, Pearl; Conley, Bridget; Nelson, Jennifer S; Free, Meghan; Martin, Aaron; Starmer, Joshua; Wilson, Elizabeth M; Su, Maureen A

    2016-01-01

    Male gender is protective against multiple sclerosis and other T-cell-mediated autoimmune diseases. This protection may be due, in part, to higher androgen levels in males. Androgen binds to the androgen receptor (AR) to regulate gene expression, but how androgen protects against autoimmunity is not well understood. Autoimmune regulator (Aire) prevents autoimmunity by promoting self-antigen expression in medullary thymic epithelial cells, such that developing T cells that recognize these self-antigens within the thymus undergo clonal deletion. Here we show that androgen upregulates Aire-mediated thymic tolerance to protect against autoimmunity. Androgen recruits AR to Aire promoter regions, with consequent enhancement of Aire transcription. In mice and humans, thymic Aire expression is higher in males compared with females. Androgen administration and male gender protect against autoimmunity in a multiple sclerosis mouse model in an Aire-dependent manner. Thus, androgen control of an intrathymic Aire-mediated tolerance mechanism contributes to gender differences in autoimmunity. PMID:27072778

  8. Cell mediated immune regulation in autoimmunity.

    PubMed

    Gillissen, G; Pusztai-Markos, Z

    1979-01-01

    Autoimmunity is the term for the immune conditions characterized by a specific humoral or cell mediated response to the body's own tissues. The termination of the natural state of self tolerance may lead to immunopathological manifestations with clinical consequences, i.e. autoimmune diseases. In a very general sense, one may classify autoimmune diseases into two groups with respect to the underlying mechanism: 1. There are autoimmune diseases which develop in the presence of a normal intact regulation mechanism. 2. Another group whose development must be understood on the basis of a cellular dysfunction. In the first case, dequestered or semi-sequestered autoantigens are liberated as a consequence of exogenic influences inducing the sensitization of immunocompetent cells. The immune system then reacts with these autoantigens in the same way as with foreign substances. This kind of autoimmune disease will, however, not be dealt with here. In the second case, autoantigens are normally, i.e. in healthy individuals, accessible to the immunocompetent cells. To understand the reason for the development of an autoimmune reaction one must first clarify the mechanism of self tolerance. Then one must examine the way in which a break of this physiological state takes place. One of the major unanswered questions is the relative importance of antibody-mediated and cell-mediated immune mechanisms in the onset and further development of autoimmune diseases. Recently it has been suggested that a dysfunction at the cellular level might represent the basic cause which induces the termination of selftolerance. Most of the conceptions about the mechanism by which autoimmune diseases are triggered were gained through experiments with animals. It is, however, difficult to use these experimental results to explain human diseases; in humans many questions are still open. Undoubtedly, the mechanisms of induction and maintenance of self tolerance and also the ways in which autoimmune

  9. Amplification of autoimmune disease by infection

    PubMed Central

    Posnett, David N; Yarilin, Dmitry

    2005-01-01

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

  10. Polyglandular autoimmune syndrome disguised as mental illness.

    PubMed

    Wei, Randy; Chang, Allen; Rockoff, Aaron

    2013-01-01

    Our case acts to highlight the numerous presentations of polyglandular autoimmune syndromes. A 62-year-old Taiwanese woman with a history of schizophrenia presented to our emergency department with a brain tumour causing her headaches. She was admitted due to severe anaemia, and after further investigation, the patient was discovered to have pernicious anaemia and autoimmune thyroiditis-consistent with the diagnosis of polyglandular autoimmune syndrome IIIb. Her underlying primary psychiatric diagnosis was then questioned. The diagnosis of her endocrinopathies were likely delayed for many years due to the psychiatric disorder which may have been due to her long-standing autoimmune hypothyroidism and/or vitamin B12 deficiency. Initial treatment brought about major behavioural improvement, and encourages physicians to investigate secondary causes of psychosis and other coexisting autoimmune diseases when a patient presents with one endocrinopathy. PMID:23632176

  11. Apoptosis in autoimmune and non-autoimmune thyroid disease.

    PubMed

    Ludgate, M; Jasani, B

    1997-06-01

    The elimination of autoreactive T cells in the thymus involves the process of programmed cell death. Animal model studies, using the lpr and gld strains of mice, have identified FAS receptor (FAS) and FAS ligand (FAS-L) as important components of this mechanism. Whether FAS and FAS-L are also implicated in the autoimmune destruction of a target organ, such as the thyroid, remain hypothetical. An accompanying paper in this issue has addressed the question by FACS and immunocytochemical analysis of FAS expression and apoptosis in thyrocytes grown in culture and in intact thyroid tissues obtained from Hashimoto's thyroiditis, multinodular goitre and Graves' disease. The overall results suggest that the degree of FAS expression on target cells may determine their sensitivity to T-cell mediated cytotoxicity in the absence of perforin or granzyme directed apoptosis mechanisms. PMID:9274519

  12. Autoimmune Neutropenia as a Cause of Periodontal Disease in Preschool Children.

    PubMed

    Hajishengallis, Evlambia; Rashewsky, Stephanie; Kulkarni, Cyelee; Stathopoulou, Panagiota

    2016-01-01

    In autoimmune neutropenia, autoantibodies attack neutrophils resulting in their destruction or alteration of their function. Since neutrophils have important immunologic functions, aberrations in their homeostasis lead to increased susceptibility to diseases, such as periodontitis. Periodontitis as a manifestation of neutropenia can affect adults and children. In this paper, we describe the treatment of periodontal disease in a 2-year-old female with autoimmune neutropenia. The importance of an interdisciplinary approach, frequent recalls, and meticulous mechanical therapy in stabilizing her periodontal condition, despite ongoing systemic infections is emphasized. PMID:26696110

  13. Enteropathy-associated intestinal T-cell lymphoma in cavitating mesenteric lymph node syndrome: fine-needle aspiration contributes to the diagnosis.

    PubMed

    Schwock, Joerg; Hyjek, Elizabeth M; Torlakovic, Emina E; Geddie, William R

    2015-02-01

    Cavitating mesenteric lymph node syndrome (CMLNS) is an infrequently reported manifestation of unrecognized/longstanding celiac disease and may be associated with enteropathy-associated intestinal T-cell lymphoma and hyposplenism. Unrecognized malignancy and life-threatening infections can pose a significant risk to patients in cases of delayed diagnosis. Fine-needle aspiration of the mesenteric lesions may contribute significantly to the correct diagnosis and can expedite patient management. We report on the cytologic characteristics of enteropathy-associated intestinal T-cell lymphoma first detected in a cyst fluid specimen obtained from a patient with cavitating mesenteric lesions. Image-guided fine-needle aspiration resulted in chylous fluid that contained a lymphoid cell population with neoplastic morphology and abnormal immunophenotype. Further work-up led to the diagnosis of enteropathy-associated intestinal T-cell lymphoma with bone marrow involvement. Cytologic assessment of the cyst fluid is an important part of the diagnostic cascade in patients with CMLNS to exclude clinically occult lymphoma. PMID:24610808

  14. Immunomodulatory vaccination in autoimmune disease.

    PubMed

    Urbanek-Ruiz, Irene; Ruiz, Pedro J; Steinman, Lawrence; Fathman, C Garrison

    2002-06-01

    The development of vaccines is arguably the most significant achievement in medicine to date. The practice of innoculation with the fluid from a sore to protect from a disease actually dates back to ancient China; however, with the introduction of Jenner's smallpox vaccine, and greater understanding of the immune system, vaccines have become specific and systematic. Traditional vaccines have used killed pathogens (hepatitis A and the Salk polio vaccines), immunogenic subunits of a given pathogen (hepatitis B subunit vaccine), or live attenuated pathogens (measles, mumps, rubella, Sabin polio vaccines) to generate protective immunity. Currently, a new generation of vaccines that use the genetic material of a pathogen to elicit protective immunity are being developed. Although the most widespread and successful use of vaccines today remains in the arena of infectious diseases, manipulations of immune responses to protect against cancers, neurologic diseases, and autoimmunity are being explored rigorously. PMID:12092460

  15. Successful pregnancy with autoimmune cirrhosis.

    PubMed

    Braga, António; Braga, Jorge

    2016-01-01

    Pregnancy with liver cirrhosis is a rare and dangerous event that exposes mother and fetus to potentially lethal risks. During pregnancy, hepatic decompensation could suffice and the development of hepatic failure and encephalopathy could occur. The incidence of obstetric complications is also increased with a high rate of pre-eclampsia, postpartum bleeding, preterm delivery and stillbirth. We report a case of a 27-year-old woman with autoimmune hepatitis and liver cirrhosis complicated by splenomegaly, oesophageal varices and severe thrombocytopaenia. During pregnancy, close clinical and analytical surveillance was performed. She was medicated with corticosteroids, azathioprine and propranolol. At the 25th week of gestation, an upper gastrointestinal endoscopy was performed to control oesophageal varices. This patient had an uneventful pregnancy until 37 weeks. At 37th week of gestation, after spontaneous rupture of membranes, signs of acute fetal distress were observed, and an urgent caesarean was performed. Good neonatal and maternal outcomes were achieved. PMID:26825934

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

    PubMed

    Cohen, Irun R

    2014-11-01

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

  17. Immunotherapeutic strategies in autoimmune uveitis

    PubMed Central

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

    2014-01-01

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

  18. Rett syndrome: An autoimmune disease?

    PubMed

    De Felice, Claudio; Leoncini, Silvia; Signorini, Cinzia; Cortelazzo, Alessio; Rovero, Paolo; Durand, Thierry; Ciccoli, Lucia; Papini, Anna Maria; Hayek, Joussef

    2016-04-01

    Rett syndrome (RTT) is a devastating neurodevelopmental disease, previously included into the autistic spectrum disorders, affecting almost exclusively females (frequency 1:10,000). RTT leads to intellective deficit, purposeful hands use loss and late major motor impairment besides featuring breathing disorders, epilepsy and increased risk of sudden death. The condition is caused in up to 95% of the cases by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Our group has shown a number of previously unrecognized features, such as systemic redox imbalance, chronic inflammatory status, respiratory bronchiolitis-associated interstitial lung disease-like lung disease, and erythrocyte morphology changes. While evidence on an intimate involvement of MeCP2 in the immune response is cumulating, we have recently shown a cytokine dysregulation in RTT. Increasing evidence on the relationship between MeCP2 and an immune dysfunction is reported, with, apparently, a link between MECP2 gene polymorphisms and autoimmune diseases, including primary Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. Antineuronal (i.e., brain proteins) antibodies have been shown in RTT. Recently, high levels of anti-N-glucosylation (N-Glc) IgM serum autoantibodies [i.e., anti-CSF114(N-Glc) IgMs] have been detected by our group in a statistically significant number of RTT patients. In the current review, the Authors explore the current evidence, either in favor or against, the presence of an autoimmune component in RTT. PMID:26807990

  19. Immunoadsorption therapy in autoimmune encephalitides

    PubMed Central

    Golombeck, Kristin S.; Bien, Corinna; Abu-Tair, Mariam; Brand, Marcus; Bulla-Hellwig, Michael; Lohmann, Hubertus; Münstermann, Dieter; Pavenstädt, Hermann; Thölking, Gerold; Valentin, Rainer; Wiendl, Heinz; Melzer, Nico; Bien, Christian G.

    2016-01-01

    Objective: It was hypothesized that in encephalitides with autoantibodies directed to CNS surface antigens an antibody-removing intervention might speed up recovery. Methods: The outcome of autoimmune encephalitis in 19 patients with antibodies against surface antigens (leucine-rich, glioma inactivated 1 [LGI1], n = 3; contactin-associated protein-2 [CASPR2], n = 4; NMDA receptor [NMDAR], n = 7) and intracellular antigens (glutamic acid decarboxylase [GAD], n = 5) after immunoadsorption in addition to corticosteroid therapy was evaluated retrospectively. Modified Rankin scale (mRS) scores and data on seizures, memory, and antibody titers directly after immunoadsorption (early follow-up) and after a median of 4 months (late follow-up) were compiled. Results: Immediately after immunoadsorption, 9 of 14 patients with antibodies against LGI1, CASPR2, or NMDAR (64%), but none with GAD antibodies, had improved by at least one mRS point. Five of the 7 patients with LGI1 or CASRP2 antibodies had become seizure-free, and 2 patients with NMDAR antibodies had a memory improvement of more than 1 SD of a normal control population. At late follow-up, 12 of 14 patients with surface antibodies had improved (86%), and none of the patients with GAD antibodies. Conclusions: It is suggested that addition of immunoadsorption to immunosuppression therapy in patients with surface antibodies may accelerate recovery. This supports the pathogenic role of surface antibodies. Classification of evidence: This study provides Class IV evidence that immunoadsorption combined with immunosuppression therapy is effective in patients with autoimmune encephalitis with surface antibodies. PMID:26977423

  20. The Diagnosis and Treatment of Autoimmune Encephalitis

    PubMed Central

    2016-01-01

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

  1. Human autoimmune diseases: a comprehensive update.

    PubMed

    Wang, Lifeng; Wang, Fu-Sheng; Gershwin, M Eric

    2015-10-01

    There have been significant advances in our understanding of human autoimmunity that have led to improvements in classification and diagnosis and, most importantly, research advances in new therapies. The importance of autoimmunity and the mechanisms that lead to clinical disease were first recognized about 50 years ago following the pioneering studies of Macfarlane Burnett and his Nobel Prize-winning hypothesis of the 'forbidden clone'. Such pioneering efforts led to a better understanding not only of autoimmunity, but also of lymphoid cell development, thymic education, apoptosis and deletion of autoreactive cells. Contemporary theories suggest that the development of an autoimmune disease requires a genetic predisposition and environmental factors that trigger the immune pathways that lead, ultimately, to tissue destruction. Despite extensive research, there are no genetic tools that can be used clinically to predict the risk of autoimmune disease. Indeed, the concordance of autoimmune disease in identical twins is 12-67%, highlighting not only a role for environmental factors, but also the potential importance of stochastic or epigenetic phenomena. On the other hand, the identification of cytokines and chemokines, and their cognate receptors, has led to novel therapies that block pathological inflammatory responses within the target organ and have greatly improved the therapeutic effect in patients with autoimmune disease, particularly rheumatoid arthritis. Further advances involving the use of multiplex platforms for diagnosis and identification of new therapeutic agents should lead to major breakthroughs within the next decade. PMID:26212387

  2. Cutting-edge issues in autoimmune orchitis.

    PubMed

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

    2012-04-01

    Autoimmune orchitis is a relevant cause of decreased fecundity in males, and it is defined as a direct aggression to the testis with the concomitant presence of anti-sperm antibodies (ASA). The presence of these specific antibodies has been observed in approximately 5-12% of infertile male partners. Primary autoimmune orchitis is defined by isolated infertility with ASA but without evidence of a systemic disease. Secondary causes of orchitis and/or testicular vasculitis are uniformly associated with autoimmune diseases, mainly in primary vasculitis such as polyarteritis nodosa, Behçet's disease, and Henoch-Schönlein purpura. The overall frequencies of acute orchitis and ASA in rheumatic diseases are 2-31% and 0-50%, respectively. The pathogenesis of primary/secondary autoimmune orchitis is not completely understood but probably involves the access of immune cells to the testicular microenvironment due to inflammation, infection or trauma, leading to apoptosis of spermatocytes and spermatids. Glucocorticoids and immunosuppressive drugs are indicated in autoimmune orchitis-associated active systemic autoimmune diseases. However, there are no standardized treatment options, and the real significance of ASA in infertile men is still controversial. Assisted reproductive technologies such as intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection (ICSI) are therapeutic options for male infertility associated with these autoantibodies. ICSI is considered to be the best choice for patients with severe sperm autoimmunity, particularly in males with low semen counts or motility. PMID:21842235

  3. Latent polyglandular autoimmune syndrome type 2 case diagnosed during a shock manifestation.

    PubMed

    Gürkan, Eren; Çetinarslan, Berrin; Güzelmansur, İsmail; Kocabaş, Beyza

    2016-07-01

    There are many types of polyglandular autoimmune syndrome (PAS). PAS type 2 is the most common type among adults. For PAS type 2 (PAS-2) diagnosis, detection of Addison's disease with autoimmune thyroid disease and/or type 1 diabetes mellitus are required. Premature ovarian insufficiency, pernicious anemia, vitiligo, alopecia, myasthenia gravis, celiac disease and autoimmune diabetes insipidus may be comorbidities of this condition. Contrary to the common belief, latent PAS is more common than the manifest forms. Here, we present a PAS-2 case diagnosed via adrenal crisis. At the time of diagnosis, the case was observed to have thyroid, adrenal and ovarian involvement. Therefore, PAS-2 and possible immunologic disorders were discussed. PMID:26806667

  4. Molecular diagnosis of autoimmune blistering diseases.

    PubMed

    Tsuruta, Daisuke; Dainichi, Teruki; Hamada, Takahiro; Ishii, Norito; Hashimoto, Takashi

    2013-01-01

    Autoimmune bullous diseases are the best-characterized autoimmune skin diseases. Molecular diagnosis of these diseases has become possible due to the identification of their target autoantigens over the past three decades. In this review, we summarize methodology for categorizing autoimmune bullous diseases by means of combinations of direct and indirect immunofluorescence techniques using normal human skin sections, rat bladder sections and COS7 cells transfected with desmocollins 1-3 encoded vectors, enzyme-linked immunosorbent assays and immunoblotting with normal human epidermal extracts, dermal extracts, purified proteins from cell cultures and recombinant proteins. PMID:23325635

  5. Autoimmune Hemolysis: A Journey through Time

    PubMed Central

    Freedman, John

    2015-01-01

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

  6. Phosphodiesterase 4-targeted treatments for autoimmune diseases

    PubMed Central

    2013-01-01

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

  7. Presence of Autoimmune Antibody in Chikungunya Infection

    PubMed Central

    Maek-a-nantawat, Wirach; Silachamroon, Udomsak

    2009-01-01

    Chikungunya infection has recently re-emerged as an important arthropod-borne disease in Thailand. Recently, Southern Thailand was identified as a potentially endemic area for the chikungunya virus. Here, we report a case of severe musculoskeletal complication, presenting with muscle weakness and swelling of the limbs. During the investigation to exclude autoimmune muscular inflammation, high titers of antinuclear antibody were detected. This is the report of autoimmunity detection associated with an arbovirus infection. The symptoms can mimic autoimmune polymyositis disease, and the condition requires close monitoring before deciding to embark upon prolonged specific treatment with immunomodulators. PMID:19997520

  8. B Cells with Regulatory Function in Animal Models of Autoimmune and Non-Autoimmune Diseases

    PubMed Central

    Lin, Mei; Wang, Zuomin; Han, Xiaozhe

    2015-01-01

    Although the identification of B cell subsets with negative regulatory functions and the definition of their mechanisms of action are recent events, the important negative regulatory roles of B cells in immune responses are now broadly recognized. There is an emerging appreciation for the pivotal role played by B cells in several areas of human diseases including autoimmune diseases and non-autoimmune diseases such as parasite infections and cancer. The recent research advancement of regulatory B cells in human disease coincides with the vastly accelerated pace of research on the bridging of innate and adaptive immune system. Current study and our continued research may provide better understanding of the mechanisms that promote regulatory B10 cell function to counteract exaggerated immune activation in autoimmune as well as non-autoimmune conditions. This review is focused on the current knowledge of BREG functions studied in animal models of autoimmune and non-autoimmune diseases. PMID:26236565

  9. Role of Complement in Autoimmune Hemolytic Anemia.

    PubMed

    Berentsen, Sigbjørn

    2015-09-01

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

  10. Cardiovascular disease biomarkers across autoimmune diseases.

    PubMed

    Ahearn, Joseph; Shields, Kelly J; Liu, Chau-Ching; Manzi, Susan

    2015-11-01

    Cardiovascular disease is increasingly recognized as a major cause of premature mortality among those with autoimmune disorders. There is an urgent need to identify those patients with autoimmune disease who are at risk for CVD so as to optimize therapeutic intervention and ultimately prevention. Accurate identification, monitoring and stratification of such patients will depend upon a panel of biomarkers of cardiovascular disease. This review will discuss some of the most recent biomarkers of cardiovascular diseases in autoimmune disease, including lipid oxidation, imaging biomarkers to characterize coronary calcium, plaque, and intima media thickness, biomarkers of inflammation and activated complement, genetic markers, endothelial biomarkers, and antiphospholipid antibodies. Clinical implementation of these biomarkers will not only enhance patient care but also likely accelerate the pharmaceutical pipeline for targeted intervention to reduce or eliminate cardiovascular disease in the setting of autoimmunity. PMID:26168705

  11. Microbiota at the crossroads of autoimmunity.

    PubMed

    Shamriz, Oded; Mizrahi, Hila; Werbner, Michal; Shoenfeld, Yehuda; Avni, Orly; Koren, Omry

    2016-09-01

    Autoimmune diseases have a multifactorial etiology including genetic and environmental factors. Recently, there has been increased appreciation of the critical involvement of the microbiota in the pathogenesis of autoimmunity, although in many cases, the cause and the consequence are not easy to distinguish. Here, we suggest that many of the known cues affecting the function of the immune system, such as genetics, gender, pregnancy and diet, which are consequently involved in autoimmunity, exert their effects by influencing, at least in part, the microbiota composition and activity. This, in turn, modulates the immune response in a way that increases the risk for autoimmunity in predisposed individuals. We further discuss current microbiota-based therapies. PMID:27392501

  12. Role of Complement in Autoimmune Hemolytic Anemia

    PubMed Central

    Berentsen, Sigbjørn

    2015-01-01

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

  13. Myeloid derived suppressor cells and autoimmunity.

    PubMed

    Boros, Peter; Ochando, Jordi; Zeher, Margit

    2016-08-01

    Myeloid-derived suppressor cells are a heterogeneous group of immature myeloid cells with immunoregulatory function. When activated and expanded, these cells can suppress T cell functions via cell-to cell interactions as well as soluble mediators. Recent studies investigated the involvement of MDSC in autoimmune diseases. Some papers have described beneficial effect of MDSC during the course of autoimmune diseases, and suggest a potential role as a treatment option, while others failed to detect these effects. Their contributions to autoimmune diseases are not fully understood, and many questions and some controversies remain as to the expansion, activation, and inhibitory functions of MDSC. This review aims to summarize current knowledge of MDSC in autoimmune disorders. PMID:27240453

  14. Deleterious versus protective autoimmunity in multiple sclerosis.

    PubMed

    Kostic, Milos; Stojanovic, Ivana; Marjanovic, Goran; Zivkovic, Nikola; Cvetanovic, Ana

    2015-08-01

    Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disorder of central nervous system, in which myelin specific CD4(+) T cells have a central role in orchestrating pathological events involved in disease pathogenesis. There is compelling evidence that Th1, Th9 and Th17 cells, separately or in cooperation, could mediate deleterious autoimmune response in MS. However, the phenotype differences between Th cell subpopulations initially employed in MS pathogenesis are mainly reflected in the different patterns of inflammation introduction, which results in the development of characteristic pathological features (blood-brain barrier disruption, demyelination and neurodegeneration), clinically presented with MS symptoms. Although, autoimmunity was traditionally seen as deleterious, some studies indicated that autoimmunity mediated by Th2 cells and T regulatory cells could be protective by nature. The concept of protective autoimmunity in MS pathogenesis is still poorly understood, but could be of great importance in better understanding of MS immunology and therefore, creating better therapeutic strategies. PMID:25944389

  15. Shaping the spectrum - From autoinflammation to autoimmunity.

    PubMed

    Hedrich, Christian M

    2016-04-01

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

  16. Role of neutrophils in systemic autoimmune diseases

    PubMed Central

    2013-01-01

    Neutrophils have emerged as important regulators of innate and adaptive immune responses. Recent evidence indicates that neutrophils display marked abnormalities in phenotype and function in various systemic autoimmune diseases, and may play a central role in initiation and perpetuation of aberrant immune responses and organ damage in these conditions. This review discusses the putative roles that neutrophils and aberrant neutrophil cell death play in the pathogenesis of various systemic autoimmune diseases, including systemic lupus erythematosus, small vessel vasculitis and rheumatoid arthritis. PMID:24286137

  17. Renal cell carcinoma and autoimmune hemolytic anemia.

    PubMed

    Lands, R; Foust, J

    1996-04-01

    A previously healthy man who became bedridden because of malaise, fatigue, and weakness was found to have an autoimmune hemolytic anemia (AIHA). In the course of his evaluation for the AIHA, he was found, coincidentally, to have a renal cell carcinoma. The AIHA was marginally responsive to therapy with corticosteroids, but it resolved promptly after excision of the cancer. This case represents probably a rarely observed association between a nonhematologic malignancy and autoimmune hemolytic anemia. PMID:8614893

  18. Intermittent cyclophosphamide treatment of autoimmune thrombocytopenia

    PubMed Central

    Weinerman, Brian; Maxwell, Ian; Hryniuk, William

    1974-01-01

    Cyclophosphamide was given intermittently rather than daily to 14 patients with autoimmune thrombocytopenic purpura. Eight patients responded and six did not. In those who responded the rise in platelet count was rapid, and in all patients the lack of toxicity was striking. Intermittent cyclophosphamide seems effective in some cases of autoimmune thrombocytopenia and is safe, at least in the short term. Controlled trials would be required to prove that intermittent is better than daily administration. PMID:4473260

  19. Effects of Ex-Vivo and In-Vivo Treatment with Probiotics on the Inflammasome in Dogs with Chronic Enteropathy

    PubMed Central

    Schmitz, Silke; Werling, Dirk; Allenspach, Karin

    2015-01-01

    Inflammasomes coordinate the maturation of IL-1β and IL-18 in response to danger signals. They are vital for maintenance of intestinal homeostasis and have been linked to chronic intestinal inflammation in humans. Probiotics have been advocated as treatment in intestinal inflammation. So far, no study has investigated the role of the inflammasome in canine chronic enteropathy (CE). In this study the intestinal expression of inflammasome components was assessed in CE dogs compared to controls, when treated with probiotic Enterococcus faecium (EF) ex-vivo and in-vivo. RNA extraction from endoscopic biopsies and reverse-transcriptase quantitative PCR was performed for NLRP3, casp-1, IL-1β and IL-18. Immunohistochemistry was performed to investigate protein expression in tissues. Gene expression of casp-1 and NLRP3 was lower in CE samples than controls. Ex-vivo treatment with EF reduced NLRP3 expression in control samples. Treatment of CE dogs with EF alongside dietary intervention had no effect on gene expression. In contrast, IL-1β protein expression in CE decreased with dietary treatment (but not with probiotics). The results of this study suggest that the inflammasome or its components may be partially involved in the inflammatory process seen in CE, but distinct from intestinal inflammation in humans. PMID:25799280

  20. Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations.

    PubMed

    Roberti, Annalisa; Dobay, Maria Pamela; Bisig, Bettina; Vallois, David; Boéchat, Cloé; Lanitis, Evripidis; Bouchindhomme, Brigitte; Parrens, Marie-Cécile; Bossard, Céline; Quintanilla-Martinez, Leticia; Missiaglia, Edoardo; Gaulard, Philippe; de Leval, Laurence

    2016-01-01

    Enteropathy-associated T-cell lymphoma (EATL), a rare and aggressive intestinal malignancy of intraepithelial T lymphocytes, comprises two disease variants (EATL-I and EATL-II) differing in clinical characteristics and pathological features. Here we report findings derived from whole-exome sequencing of 15 EATL-II tumour-normal tissue pairs. The tumour suppressor gene SETD2 encoding a non-redundant H3K36-specific trimethyltransferase is altered in 14/15 cases (93%), mainly by loss-of-function mutations and/or loss of the corresponding locus (3p21.31). These alterations consistently correlate with defective H3K36 trimethylation. The JAK/STAT pathway comprises recurrent STAT5B (60%), JAK3 (46%) and SH2B3 (20%) mutations, including a STAT5B V712E activating variant. In addition, frequent mutations in TP53, BRAF and KRAS are observed. Conversely, in EATL-I, no SETD2, STAT5B or JAK3 mutations are found, and H3K36 trimethylation is preserved. This study describes SETD2 inactivation as EATL-II molecular hallmark, supports EATL-I and -II being two distinct entities, and defines potential new targets for therapeutic intervention. PMID:27600764

  1. Extranodal multiple involvement of enteropathy-type T-cell lymphoma without expression of CC chemokine receptor 7.

    PubMed

    Shiratsuchi, Motoaki; Suehiro, Youko; Yoshikawa, Yasuji; Ohshima, Koichi; Shiokawa, Satoshi; Nishimura, Junji

    2004-01-01

    Enteropathy-type T-cell lymphoma (ETCL) is a rare extranodal lymphoma that tends to disseminate into the intestines and other extranodal organs. We present a case of ETCL with involvement of the lungs and kidneys and report CC chemokine receptor 7 (CCR7) expression of lymphoma cells. A 73-year-old man was admitted to the hospital with a complaint of abdominal pain. Multiple ulcers and perforations were observed in the small intestine, and partial resection of the ileum was performed. Histological examination of the resected specimen revealed diffuse proliferation of atypical large lymphoid cells. The diagnosis was ETCL with dissemination into the lungs and kidney. Lymphoma cells of the small intestine and in pleural effusion were CD3+, CD4+, CD7+, CD8-, CD25-, CD56-, CD103 +/-, and TIA-1+. Rearrangement of the T-cell receptor beta gene was detected, and human T-lymphotropic virus was not integrated. Combination chemotherapy did not result in a sustained response. The results for CCR7 expression of lymphoma cells in the lung and pleural effusion were negative. Therefore we concluded that lymphoma cells did not migrate into the lymph nodes but instead spread into the extranodal organs. PMID:14979477

  2. Recovery of graft steatosis and protein-losing enteropathy after biliary diversion in a PFIC 1 liver transplanted child.

    PubMed

    Nicastro, Emanuele; Stephenne, Xavier; Smets, Françoise; Fusaro, Fabio; de Magnée, Catherine; Reding, Raymond; Sokal, Etienne M

    2012-08-01

    PFIC 1 is a genetic disorder characterized by hepatic and gastrointestinal disease, often requiring LT during childhood. Extrahepatic symptoms, such as diarrhea and malabsorption, do not improve or may be aggravated after LT, as graft steatosis or steatohepatitis as consequences of the interaction between transplanted liver and native bowel. We describe a patient with PFIC 1 who presented with cholestasis in infancy, who developed intractable pruritus and liver fibrosis. The child underwent living donor LT at 3.6 yr of age, and he early developed severe refractory diarrhea, secondary malabsorption with protein-losing enteropathy, and an early fatty liver disease trough graft steatohepatitis. As the response to cholestyramine was unsatisfactory, we decided to perform an EBD by using the jejunal loop used for the cholangiojejunostomy. Diarrhea resolved rapidly after surgery. He remained well after six months following biliary diversion, with normal stool output and no protein loss. We documented a dramatic improvement of graft steatosis at histology as well as normalization of liver function test. EBD can be considered a valuable treatment option to avoid organ disfunction and loss in PFIC 1 transplanted patients who develop graft steatohepatitis. PMID:21672103

  3. A Novel SMAD4 Mutation Causing Severe Juvenile Polyposis Syndrome with Protein Losing Enteropathy, Immunodeficiency, and Hereditary Haemorrhagic Telangiectasia

    PubMed Central

    Johansson, Joel; Sahin, Christofer; Pestoff, Rebecka; Ignatova, Simone; Forsberg, Pia; Edsjö, Anders; Ekstedt, Mattias; Stenmark Askmalm, Marie

    2015-01-01

    Juvenile polyposis syndrome (JPS) is a rare genetic disorder characterized by juvenile polyps of the gastrointestinal tract. We present a new pathogenic mutation of the SMAD4 gene and illustrate the need for a multidisciplinary health care approach to facilitate the correct diagnosis. The patient, a 47-year-old Caucasian woman, was diagnosed with anaemia at the age of 12. During the following 30 years, she developed numerous gastrointestinal polyps. The patient underwent several operations, and suffered chronic abdominal pain, malnutrition, and multiple infections. Screening of the SMAD4 gene revealed a novel, disease-causing mutation. In 2012, the patient suffered hypoalbuminemia and a large polyp in the small bowel was found. Gamma globulin was given but the patient responded with fever and influenza-like symptoms and refused more treatment. The patient underwent surgery in 2014 and made an uneventful recovery. At follow-up two months later albumin was 38 g/L and IgG was 6.9 g/L. Accurate diagnosis is essential for medical care. For patients with complex symptomatology, often with rare diseases, this is best provided by multidisciplinary teams including representatives from clinical genetics. Patients with a SMAD4 mutation should be followed up both for JPS and haemorrhagic hereditary telangiectasia and may develop protein loosing enteropathy and immunodeficiency. PMID:25705527

  4. Circulating IGF-I and IGFBP3 levels control human colonic stem cell function and are disrupted in diabetic enteropathy

    PubMed Central

    Maestroni, Anna; Jung, Peter; Orsenigo, Elena; Nasr, Moufida Ben; Tezza, Sara; Bassi, Roberto; Finzi, Giovanna; Marando, Alessandro; Vergani, Andrea; Frego, Roberto; Albarello, Luca; Andolfo, Annapaola; Manuguerra, Roberta; Viale, Edi; Staudacher, Carlo; Corradi, Domenico; Batlle, Eduard; Breault, David; Secchi, Antonio; Folli, Franco; Fiorina, Paolo

    2016-01-01

    Summary The role of circulating factors in regulating colonic stem cells (CoSCs) and colonic epithelial homeostasis is unclear. Individuals with long-standing type 1 diabetes (T1D) frequently have intestinal symptoms, termed diabetic enteropathy (DE), though its etiology is unknown. Here, we report T1D patients with DE exhibit abnormalities in their intestinal mucosa and CoSCs, which fail to generate in vitro mini-guts. Proteomic profiling of T1D+DE patient serum revealed altered levels of insulin-like growth factor 1 (IGF-1) and its binding protein-3 (IGFBP3). IGFBP3 prevented in vitro growth of patient-derived organoids via binding its receptor TMEM219, in an IGF-1-independent manner, and disrupted in vivo CoSC function in a preclinical DE model. Restoration of normoglycemia in patients with long-standing T1D via kidney-pancreas transplantation or in diabetic mice by treatment with an ecto-TMEM219 recombinant protein normalized circulating IGF-1/IGFBP3 levels and reestablished CoSC homeostasis. These findings demonstrate that peripheral IGF-1/IGFBP3 control CoSCs and their dysfunction in DE. PMID:26431183

  5. Biochemical changes in the jejunal mucosa of dogs with a naturally occurring enteropathy associated with bacterial overgrowth.

    PubMed Central

    Batt, R M; Carter, M W; Peters, T J

    1984-01-01

    The subcellular biochemical features of a naturally occurring enteropathy in the dog associated with bacterial overgrowth have been examined. Affected animals comprised a group of 10 German Shepherd dogs with raised serum folate and reduced vitamin B12 concentrations, mild steatorrhoea, reduced xylose absorption, and normal exocrine pancreatic function. Culture of duodenal juice showed bacterial overgrowth with mixed flora, most frequently including enterococci and Escherichia coli. Examination of peroral jejunal biopsies revealed predominantly minimal histological but distinct biochemical abnormalities in the mucosa. The specific activity of alkaline phosphatase was decreased, isopycnic density gradient centrifugation showing a marked loss particularly of the brush border component of enzyme activity. In contrast, gamma-glutamyl transferase activity was enhanced in brush border fragments of slightly increased modal density, but there were no changes in the activities of the carbohydrases, zinc-resistant alpha-glucosidase, maltase, sucrase, and lactase or of the peptidase, leucyl-2-naphthylamidase. Activities of lysosomal enzymes were increased and there was evidence for enhanced lysosomal fragility and mitochondrial disruption. The activities and density gradient distributions of marker enzymes for basal-lateral membranes, endoplasmic reticulum and peroxisomes were essentially unaltered. These findings show that bacterial colonisation of the proximal small intestine may be associated with specific alterations in microvillus membrane proteins and provide biochemical evidence for intracellular damage to the enterocytes. PMID:6745719

  6. [Protein-loosing enteropathy: report of four cases and review of etiology, diagnostic work-up and treatment].

    PubMed

    Bindl, L; Buderus, S; Bindl, C; Lentze, M J

    2005-01-01

    The protein-loosing enteropathy (PLE) may result from a broad variety of underlying diseases. These conditions are of systemic nature or locally affecting the gastrointestinal tract. Major symptoms are oedema due to low plasma protein levels. Gastrointestinal symptoms are not necessarily present. The diagnosis is confirmed by the finding of increased faecal concentrations of Alpha-1-Antitrypsin (> 320 mg/L). In the majority of cases, in which underlying diseases are present, the etiology is obvious. In unclear cases the differentiation into inflammatory or circulatory disturbances or alterations of the architecture of the basal membrane is helpful. An economic, staged approach is presented. To localize the site of protein loss imaging is required (abdominal ultrasound, CT-scan, endoscopy and Technetium-Scan). If a circumscribed intestinal source of protein loss is suspected which may be amenable to surgery, intraoperative enteroscopy should be considered. If causal treatment is impossible; intravenous replacement of albumin and immunoglobulines in intervals from 1 to 4 weeks will be necessary. The prognosis in patients with isolated PLE is good. Otherwise it depends on the underlying disease. PMID:16032545

  7. [Autoimmune connective tissue diseases and vaccination].

    PubMed

    Więsik-Szewczyk, Ewa; Jahnz-Różyk, Karina

    2015-01-01

    The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently sensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group. PMID:27259225

  8. Autoimmune encephalitis and its relation to infection.

    PubMed

    Venkatesan, Arun; Benavides, David R

    2015-03-01

    Encephalitis, an inflammatory condition of the brain that results in substantial morbidity and mortality, has numerous causes. Over the past decade, it has become increasingly recognized that autoimmune conditions contribute significantly to the spectrum of encephalitis causes. Clinical suspicion and early diagnosis of autoimmune etiologies are of particular importance due to the need for early institution of immune suppressive therapies to improve outcome. Emerging clinical observations suggest that the most commonly recognized cause of antibody-mediated autoimmune encephalitis, anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, may in some cases be triggered by herpes virus infection. Other conditions such as Rasmussen's encephalitis (RE) and febrile infection-related epilepsy syndrome (FIRES) have also been posited to be autoimmune conditions triggered by infectious agents. This review focuses on emerging concepts in central nervous system autoimmunity and addresses clinical and mechanistic findings linking autoimmune encephalitis and infections. Particular consideration will be given to anti-NMDA receptor encephalitis and its relation to herpes simplex encephalitis. PMID:25637289

  9. Autoimmune liver disease in Noonan Syndrome.

    PubMed

    Loddo, Italia; Romano, Claudio; Cutrupi, Maria Concetta; Sciveres, Marco; Riva, Silvia; Salpietro, Annamaria; Ferraù, Valeria; Gallizzi, Romina; Briuglia, Silvana

    2015-03-01

    Noonan Syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The syndrome is transmitted as an autosomal dominant trait. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein. Autoimmune Hepatitis (AIH) is a cryptogenic, chronic and progressive necroinflammatory liver disease. Common features of AIH are hypergammaglobulinemia (IgG), presence of circulating autoantibodies, histological picture of interface hepatitis and response to immunosuppressant drugs. Conventional treatment with Prednisone and Azathioprine is effective in most patients. We describe the case of a 6 years-old girl with Noonan Syndrome and Autoimmune Hepatitis type 1. Molecular analysis of PTPN11 gene showed heterozygous mutation c.923A>G (Asn308Ser) in exon 8. Though association between NS and autoimmune disorders is known, this is the second case of association between Noonan Syndrome and Autoimmune Hepatitis type 1 described in literature. In the management of NS, an accurate clinical evaluation would be recommended. When there is a clinical suspicion of autoimmune phenomena, appropriate laboratory tests should be performed with the aim of clarifying whether the immune system is involved in NS. We think that autoimmunity represents a characteristic of NS, even if the etiopathogenesis is still unknown. PMID:25595571

  10. Environmental Exposures and Autoimmune Thyroid Disease

    PubMed Central

    2010-01-01

    Background Environmental exposures, ranging from perchlorate in rocket fuel to polychlorinated biphenols, have been shown to influence thyroid function. Although most of these agents are associated with reduced thyroid hormone levels or impaired thyroid hormone action, a number of environmental exposures confer an increased risk of autoimmune thyroid disease. Summary Factors that increase autoimmune thyroid disease risk include radiation exposure, both from nuclear fallout and medical radiation, increased iodine intake, as well as several contaminants in the environment that influence the thyroid. Although ∼70% of the risk for developing autoimmune thyroid disease is attributable to genetic background, environmental triggers are thought to play a role in the development of autoimmune thyroid disease in susceptible individuals. Conclusions Understanding the association of environmental agents with thyroid dysfunction can be utilized to reduce the risk to populations. Knowledge of the specific factors that trigger autoimmune thyroid disease and their mode of action, however, may also inform risk reduction in the individual patient. These factors are especially relevant for those at increased risk of autoimmune thyroid disease based on family history. PMID:20578899

  11. Secondary autoimmune cytopenias in chronic lymphocytic leukemia.

    PubMed

    Rogers, Kerry A; Woyach, Jennifer A

    2016-04-01

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

  12. Solving the puzzle of autoimmunity: critical questions

    PubMed Central

    Smilek, Dawn E.

    2015-01-01

    Despite recent advances in delineating the pathogenic mechanisms of autoimmune disease, the puzzle that reveals the true picture of these diverse immunological disorders is yet to be solved. We know that the human leukocyte antigen (HLA) loci as well as many different genetic susceptibility loci with relatively small effect sizes predispose to various autoimmune diseases and that environmental factors are involved in triggering disease. Models for mechanisms of disease become increasingly complex as relationships between components of both the adaptive and innate immune systems are untangled at the molecular level. In this article, we pose some of the important questions about autoimmunity where the answers will advance our understanding of disease pathogenesis and improve the rational design of novel therapies. How is autoimmunity triggered, and what components of the immune response drive the clinical manifestations of disease? What determines whether a genetically predisposed individual will develop an autoimmune disease? Is restoring immune tolerance the secret to finding cures for autoimmune disease? Current research efforts seek answers to these big questions. PMID:25750735

  13. Smell and autoimmunity: a comprehensive review.

    PubMed

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

    2013-08-01

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

  14. Virus infection, antiviral immunity, and autoimmunity

    PubMed Central

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

    2014-01-01

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

  15. [Thrombophilia, autoimmunity, and perioperative thromboprophylaxis].

    PubMed

    Rubio-Jurado, Benjamín; Salazar-Páramo, Mario; Medrano-Múnoz, Fabiola; González-Ojeda, Alejandro; Nava, Arnulfo

    2007-01-01

    Thrombosis is observed in several areas of medicine. Equilibrium between pro- and anticoagulant factors is required for maintaining blood flow. Tissue injury from multiple causes may induce coagulum formation mediated by coagulation pathway activation. Tissue factor (F III) + F VIIa interacts with both platelet and endothelial cell receptors. This coagulation model displays four stages: a) initiation, b) amplification, c) propagation and d) stabilization. Development of thrombosis is associated with either primary or hereditary and acquired factors. Primary thrombophilia is determined genetically by a hypercoagulative state shown by loss of natural anticoagulant activity, such as antithrombin III, C, S protein or procoagulant activity gaining resistance to activated C protein: factor V (Leiden), prothrombin and methylenetetrahydrofolate reductase mutations. Acquired thrombophilia mainly relates to an autoimmune condition such as the presence of anticardiolipin antibodies or lupus anticoagulant. Surgical procedures enhance mechanisms that predispose to thrombosis, e.g., acidosis, hypothermia, plasma expanders, extracorporeal circulation, duration of surgical procedure, and tissue manipulation. Adequate classification of the patient's thrombosis risk and adequate use of primary and secondary prophylactic recommendations in these groups of patients is necessary. PMID:18053365

  16. [Autoimmune thyroiditis and thyroid cancer].

    PubMed

    Krátký, Jan; Jiskra, Jan

    2015-10-01

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

  17. Autoimmune neurologic disorders in children.

    PubMed

    Lim, Ming; Gorman, Mark

    2016-01-01

    Autoimmune neurologic diseases are of major clinical importance in children. Antibody-mediated diseases of the central nervous system are now increasingly recognized in childhood, where the antibodies bind to cell surface epitopes on neuronal or glial proteins, and the patients demonstrate either focal or more generalized clinical signs depending on the extent of brain regions targeted by the antibodies. The antibodies are directed towards ion channels, receptors, and membrane proteins; and the diseases include limbic encephalitis and N-methyl-d-aspartate receptor-antibody encephalitis, among many others. Additionally there are conditions where the wider immune system is implicated. Neurologic features like seizures, movement disorders, autonomic dysfunction, and sleep disorders, with neuroimaging and electrophysiologic features, may indicate a specific antibody-mediated or immune disorder. Often, phenotypic overlap is observed between these conditions, and phenotypic variation seen in children with the same condition. Nevertheless, many patients benefit from immunotherapy with substantial improvement, although huge efforts are still required to optimize the outcome for many patients. In many patients no antibodies have yet been identified, even though they respond to immunotherapies. Here we describe the known antibodies and associated diseases, discuss conditions that are thought to be immune-mediated but have no known immunologic biomarker, and provide guidelines for the investigation and classification of these disorders. PMID:27112693

  18. The autoimmune basis of narcolepsy.

    PubMed

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

    2013-10-01

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

  19. Treatment of autoimmune hemolytic anemias

    PubMed Central

    Zanella, Alberto; Barcellini, Wilma

    2014-01-01

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

  20. Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations.

    PubMed

    Tomljenovic, L; Shaw, C A

    2012-02-01

    Immune challenges during early development, including those vaccine-induced, can lead to permanent detrimental alterations of the brain and immune function. Experimental evidence also shows that simultaneous administration of as little as two to three immune adjuvants can overcome genetic resistance to autoimmunity. In some developed countries, by the time children are 4 to 6 years old, they will have received a total of 126 antigenic compounds along with high amounts of aluminum (Al) adjuvants through routine vaccinations. According to the US Food and Drug Administration, safety assessments for vaccines have often not included appropriate toxicity studies because vaccines have not been viewed as inherently toxic. Taken together, these observations raise plausible concerns about the overall safety of current childhood vaccination programs. When assessing adjuvant toxicity in children, several key points ought to be considered: (i) infants and children should not be viewed as "small adults" with regard to toxicological risk as their unique physiology makes them much more vulnerable to toxic insults; (ii) in adult humans Al vaccine adjuvants have been linked to a variety of serious autoimmune and inflammatory conditions (i.e., "ASIA"), yet children are regularly exposed to much higher amounts of Al from vaccines than adults; (iii) it is often assumed that peripheral immune responses do not affect brain function. However, it is now clearly established that there is a bidirectional neuro-immune cross-talk that plays crucial roles in immunoregulation as well as brain function. In turn, perturbations of the neuro-immune axis have been demonstrated in many autoimmune diseases encompassed in "ASIA" and are thought to be driven by a hyperactive immune response; and (iv) the same components of the neuro-immune axis that play key roles in brain development and immune function are heavily targeted by Al adjuvants. In summary, research evidence shows that increasing concerns

  1. Analysis of the autoimmune regulator gene in patients with autoimmune non-APECED polyendocrinopathies.

    PubMed

    Palma, Alessia; Gianchecchi, Elena; Palombi, Melania; Luciano, Rosa; Di Carlo, Pierluigi; Crinò, Antonino; Cappa, Marco; Fierabracci, Alessandra

    2013-09-01

    The pathogenesis of autoimmunity was derived from a complex interaction of genetic and environmental factors. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene. AIRE gene variants and, in particular, heterozygous loss-of-function mutations were also discovered in organ-specific autoimmune disorders, possibly contributing to their etiopathogenesis. It was suggested that even predisposition to develop certain autoimmune conditions may be derived from AIRE gene polymorphisms including S278R and intronic IVS9+6 G>A. In this study we unravel the hypothesis on whether AIRE gene variants may predispose individuals to associated autoimmune conditions in 41 Italian patients affected by non-APECED autoimmune polyendocrinopathies. We could not detect any heterozygous mutations of the AIRE gene. Although a trend of association was observed, heterozygous polymorphisms S278R and IVS9+6 G>A were detected in patients without statistically significant prevalence than in controls. Their putative contribution to autoimmune polyendocrinopathies and their predictive value in clinical strategies of disease development could be unravelled by analysing a larger sample of diseased patients and healthy individuals. PMID:23643663

  2. Role of IgE in autoimmunity.

    PubMed

    Sanjuan, Miguel A; Sagar, Divya; Kolbeck, Roland

    2016-06-01

    There is accumulating evidence to suggest that IgE plays a significant role in autoimmunity. The presence of circulating self-reactive IgE in patients with autoimmune disorders has been long known but, at the same time, largely understudied. However, studies have shown that the increased IgE concentration is not associated with higher prevalence for atopy and allergy in patients with autoimmune diseases, such as systemic lupus erythematosus. IgE-mediated mechanisms are conventionally known to facilitate degranulation of mast cells and basophils and promote TH2 immunity, mechanisms that are not only central to mounting an appropriate defense against parasitic worms, noxious substances, toxins, venoms, and environmental irritants but that also trigger exuberant allergic reactions in patients with allergies. More recently, IgE autoantibodies have been recognized to participate in the self-inflicted damaging immune responses that characterize autoimmunity. Such autoimmune responses include direct damage on tissue-containing autoantigens, activation and migration of basophils to lymph nodes, and, as observed most recently, induction of type 1 interferon responses from plasmacytoid dendritic cells. The importance of IgE as a central pathogenic mechanism in autoimmunity has now been clinically validated by the approval of omalizumab, an anti-IgE mAb, for patients with chronic spontaneous urticaria and for the clinical benefit of patients with bullous pemphigoid. In this review we summarize recent reports describing the prevalence of self-reactive IgE and discuss novel findings that incriminate IgE as central in the pathogenesis of inflammatory autoimmune disorders. PMID:27264000

  3. Neuromyelitis optica spectrum disorders without and with autoimmune diseases

    PubMed Central

    2014-01-01

    Background Neuromyelitis optica spectrum disorder (NMOSD) can coexist with non-organ-specific or organ-specific autoimmune diseases. The aim of this study was to investigate and compare the features between NMOSD without and with autoimmune diseases, and NMOSD with non-organ-specific and organ-specific autoimmune diseases. Methods One hundred and fifty five NMOSD patients without autoimmune diseases (n = 115) and with autoimmune diseases (n = 40) were enrolled. NMOSD with autoimmune diseases were divided by organ-specific autoimmune diseases. The clinical, laboratory and magnetic resonance imaging features between two groups were assessed. Results Motor deficit was less frequent in NMOSD patients with non-organ-specific autoimmune diseases (p = 0.024). Cerebrospinal fluid white blood cell and protein, serum C-reactive protein and immunoglobulin G were lower in NMOSD patients without autoimmune diseases, while several autoantibodies seropositivity and thyroid indexes were significantly higher in NMOSD patients with autoimmune diseases (p < 0.05). No difference was found in other clinical and laboratory characteristics between different NMOSD subtypes (p > 0.05). NMOSD patients with autoimmune diseases had higher brain abnormalities than NMOSD without autoimmune diseases (p < 0.001). Conclusions The characteristics between NMOSD without and with autoimmune diseases were similar. NMOSD with autoimmune diseases have high frequency of brain abnormalities. PMID:25135481

  4. Impaired hapten sensitization in patients with autoimmune disease

    PubMed Central

    Bangsgaard, N; Engkilde, K; Menné, T; Løvendorf, M; Jacobsen, G K; Olsen, J; Skov, L

    2011-01-01

    An inverse relation between contact allergy and autoimmune diseases is suggested from epidemiological studies. The aim of this study was to investigate susceptibility and reactivity in patients with psoriasis, patients with diabetes and healthy controls in an experimental sensitization study. We sensitized 68 adult individuals (23 patients with psoriasis, 22 patients with diabetes and 23 healthy controls) with diphenylcyclopropenone (DPCP) and assessed challenge responses with visual scoring and ultrasound. Skin biopsies from challenged skin were investigated for differences in down-regulatory mechanisms with immunohistochemistry and gene-expression profiles using microarray technology. The sensitization ratios were 26%, 36% and 65% for the psoriatic, diabetic and healthy groups, respectively. Logistic regression analysis gave an odds ratio (OR) for a patient with psoriasis or diabetes type I of being sensitized to 0·18 [95% confidence interval (CI): 0·039–0·85], P = 0·031 and 0·74 (95% CI: 0·548–1·008), P = 0·056, respectively. A high degree of forkhead box P3-positive (FoxP3+) cells were found in biopsies of positively challenged reactions, but only limited numbers in negatively challenged reactions, with no difference among the groups. No specific mRNA expression was found in the challenged skin of negative elicitation reactions, also indicating no sign of active down-regulation. The study contibutes strongly to the evidence of a decreased susceptibility to develop contact allergy in individuals with autoimmune diseases such as psoriasis. PMID:21668897

  5. Impaired hapten sensitization in patients with autoimmune disease.

    PubMed

    Bangsgaard, N; Engkilde, K; Menné, T; Løvendorf, M; Jacobsen, G K; Olsen, J; Skov, L

    2011-09-01

    An inverse relation between contact allergy and autoimmune diseases is suggested from epidemiological studies. The aim of this study was to investigate susceptibility and reactivity in patients with psoriasis, patients with diabetes and healthy controls in an experimental sensitization study. We sensitized 68 adult individuals (23 patients with psoriasis, 22 patients with diabetes and 23 healthy controls) with diphenylcyclopropenone (DPCP) and assessed challenge responses with visual scoring and ultrasound. Skin biopsies from challenged skin were investigated for differences in down-regulatory mechanisms with immunohistochemistry and gene-expression profiles using microarray technology. The sensitization ratios were 26%, 36% and 65% for the psoriatic, diabetic and healthy groups, respectively. Logistic regression analysis gave an odds ratio (OR) for a patient with psoriasis or diabetes type I of being sensitized to 0·18 [95% confidence interval (CI): 0·039-0·85], P = 0·031 and 0·74 (95% CI: 0·548-1·008), P = 0·056, respectively. A high degree of forkhead box P3-positive (FoxP3(+) ) cells were found in biopsies of positively challenged reactions, but only limited numbers in negatively challenged reactions, with no difference among the groups. No specific mRNA expression was found in the challenged skin of negative elicitation reactions, also indicating no sign of active down-regulation. The study contibutes strongly to the evidence of a decreased susceptibility to develop contact allergy in individuals with autoimmune diseases such as psoriasis. PMID:21668897

  6. Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

    PubMed Central

    Teixeira, Antonio R. L.; Hecht, Mariana M.; Guimaro, Maria C.; Sousa, Alessandro O.; Nitz, Nadjar

    2011-01-01

    Summary: Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8+ γδ, and CD8α+ T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease. PMID:21734249

  7. Autoimmunity and auto-immune syndromes associated with and preceding the development of lymphoproliferative disorders.

    PubMed

    Polliack, A; Lugassy, G

    1992-11-01

    In this report the association of autoimmunity and autoimmune syndromes with lymphoproliferative disorders (LPD) is described in 15 patients. Non-Hodgkin's lymphoma (NHL) developed in 10 patients, Hodgkin's disease (HD) in 3 and chronic lymphocytic leukemia (CLL) in two. In most instances clinical and laboratory phenomena preceded the development/diagnosis of these disorders. Manifestations ranged from the presence of autoantibodies in the serum to the presence of both ill defined or incomplete autoimmune syndromes including cold urticaria, Raynaud's phenomenon, cold agglutinin disease, thyroiditis, nephrotic syndrome and vasculitis to typical systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and even one of scleroderma. It is suggested that in some patients (in)complete clinical manifestations of autoimmunity may precede the development of lymphoid neoplasias. The link between autoimmunity and lymphoproliferative disorders is briefly discussed. PMID:1434818

  8.  An autoimmune polyglandular syndrome complicated with celiac disease and autoimmune hepatitis.

    PubMed

    Dieli-Crimi, Romina; Núñez, Concepción; Estrada, Lourdes; López-Palacios, Natalia

    2016-01-01

     Autoimmune polyglandular syndrome (APS) is a combination of different autoimmune diseases. The close relationship between immune-mediated disorders makes it mandatory to perform serological screening periodically in order to avoid delayed diagnosis of additional autoimmune diseases. We studied a patient with type 1 diabetes (T1D) who later developed an autoimmune thyroid disease (ATD) and was referred to our hospital with a serious condition of his clinical status. The patient was suffering from an advance stage of celiac disease (CD), the delay in its diagnosis and in the establishment of a gluten-free dietled the patient to a severe proteincalorie malnutrition. Later, the patient developed an autoimmune hepatitis (AIH). We consider that clinical deterioration in patients with APS should alert physicians about the possible presence of other immune-mediated diseases. Periodic screening for autoantibodies would help to prevent delayed diagnosis and would improve patient's quality of life. PMID:27236159

  9. Autoimmune Encephalitis in Postpartum Psychosis

    PubMed Central

    Bergink, Veerle; Armangue, Thaís; Titulaer, Maarten J.; Markx, Sander; Dalmau, Josep; Kushner, Steven A.

    2016-01-01

    Objective Significant immunological alterations have been observed in women with first-onset affective psychosis during the postpartum period. Recent studies have highlighted the possibility that a subset of patients with first-onset severe psychiatric episodes might suffer from undiagnosed autoimmune encephalitis. Therefore, the authors performed a three-step immunohistochemistry-based screening for CNS autoantibodies in a large cohort of patients with postpartum psychosis and matched postpartum comparison subjects. Method Ninety-six consecutive patients with postpartum psychosis and 64 healthy postpartum women were included. Screening for antibodies in patient serum was performed using immunohistochemistry. Samples showing any staining were further examined by immunocytochemistry using live hippocampal neurons and cell-based assays to test for anti-N-methyl-d-aspartate (NMDA) receptor antibodies. Cell-based assays for all other known CNS antigens were performed in those samples with immunocytochemistry labeling but negative for NMDA receptor antibodies. Results Four patients (4%) with neuropil labeling suggestive for extracellular antigen reactivity were identified. Serum samples from all four patients showed clear extracellular labeling of live hippocampal neurons. Two women had the specific staining pattern characteristic for anti-NMDA receptor antibody positivity, which was confirmed by cell-based assays. Neither patient with anti-NMDA receptor antibody positivity had evidence of an ovarian teratoma. The other two patients tested negative by cell-based assays for all known CNS antigens. None of the matched postpartum comparison subjects had confirmed neuronal surface antibodies. The two patients with anti-NMDA receptor antibodies both showed extrapyramidal symptoms following initiation of treatment with low-dose haloperidol. Conclusions In patients with acute psychosis during the postpartum period, systematic screening for anti-NMDA receptor autoantibodies

  10. Protective autoimmunity in cancer (review).

    PubMed

    Toubi, E; Shoenfeld, Y

    2007-01-01

    Not all malignant cells progress to invasive cancer, some may even regress, but the early detection of abnormal cells can be crucial for patient survival. Immune surveillance mechanisms are complex and provide continuous efforts for the removal of transformed cells. Naturally occurring antibodies are frontier soldiers that act as the first line of defense in the battle against cancer. During the process of carcinogenesis naturally occurring antibody responses to tumor antigens were found to be associated with improved survival and protection against the spread of cancer. Using the human hybridoma technology, a series of tumor-binding antibodies can be isolated as they have several common features: they are germ-line coded IgM antibodies, they bind to various tumor-antigens, they induce apoptosis of malignant cells, and most importantly they detect not only malignant cells but also the precursor stages (i.e., autoantigens). Natural protective autoantibodies against tumor-antigens were isolated from patients and healthy donors reflecting the development of naturally occurring B-cell responses during the process of cancer evolvement. They fulfill the definition of autoantibodies since they are self-reactive and they also bind altered self-antigens such as tumor cells. In this regard various autoantibodies such as anti-dsDNA and anti-Fas autoantibodies were found to be significantly higher in patients with various carcinomas, thus playing a role for their improved survival. Targeting T-regulatory cells, namely the expression of CTLA-4 was also found to improve survival in cancer patients. Autoimmunity and malignancy frequently coexist and they may share etiological and pathological mechanisms. Therefore, the efficacy of intravenous immunoglobulins or CTLA-4 blockade was also employed as a treatment for prevention of malignancy and metastases spread. PMID:17143505

  11. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children

    PubMed Central

    Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R.

    2016-01-01

    We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation. PMID:27622194

  12. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children.

    PubMed

    Bolia, Rishi; Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R

    2016-07-01

    We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation. PMID:27622194

  13. Complicating autoimmune diseases in myasthenia gravis: a review

    PubMed Central

    Nacu, Aliona; Andersen, Jintana Bunpan; Lisnic, Vitalie; Owe, Jone Furlund; Gilhus, Nils Erik

    2015-01-01

    Abstract Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis. PMID:25915571

  14. Autoimmunity in connection with a metal implant: a case of autoimmune/autoinflammatory syndrome induced by adjuvants.

    PubMed

    Loyo, Esthela; Jara, Luis J; López, Persio David; Puig, Ana Carolina

    2013-04-01

    Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) has been recently proposed by Shoenfeld and Agmon-Levin as a new entity that comprises several conditions: the macrophagic-myofasciitis syndrome, the Gulf War syndrome, silicosis and post-vaccination phenomena, autoimmunity related to infectious fragments, hormones, aluminum, silicone, squalene oil, and pristane. We report the case of a 23-year-old woman who developed serial episodes of high fever, extreme fatigue, transient thrombocytopenia, multiple cervical adenopathies, hepatosplenomegaly, anemia, neutropenia, severe proteinuria and urine sediment abnormalities, elevated serum ferritin levels, and transient low positive antinuclear antibodies 1 year after she had a nickel-titanium chin implant for cosmetic reasons. The clinical picture simulated a variety of probable diseases: systemic lupus erythematosus, Kikuchi-Fujimoto syndrome, adult onset Still's disease, antiphospholipid syndrome, and hemophagocytic syndrome, among others, so she underwent an extensive medical investigation including two lymph node biopsies. She received treatment accordingly with steroids, methotrexate, and mofetil mycophenolate, with initial improvement of her symptoms, which recurred every time the dose was reduced. Two and a half years later the patient decided to retire the chin implant and afterwards all her systemic symptoms have disappeared. She remains in good health, without recurrence of any symptom and off medications until today. Albeit this patient fulfills proposed major ASIA criteria, to our knowledge it would be the first description of systemic features of autoinflammation in connection with a metal implant. PMID:26000140

  15. Molecular Diagnosis in Autoimmune Skin Blistering Conditions

    PubMed Central

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

    2014-01-01

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

  16. Autoimmune gastritis: Pathologist’s viewpoint

    PubMed Central

    Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo

    2015-01-01

    Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling. PMID:26576102

  17. Neurologic autoimmunity: mechanisms revealed by animal models.

    PubMed

    Bradl, Monika; Lassmann, Hans

    2016-01-01

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

  18. How I treat autoimmune lymphoproliferative syndrome

    PubMed Central

    Oliveira, João Bosco

    2011-01-01

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

  19. Autoimmune Hemolytic Anemia and Hodgkin's Disease: An Unusual Pediatric Association

    PubMed Central

    Gomes, Maria Miguel; Oliva, Tereza; Pinto, Armando

    2016-01-01

    Autoimmune hemolytic anemia (AIHA) is a recognized complication of lymphoproliferative disorders. AIHA associated with Hodgkin's disease (HD) is uncommon especially in the pediatric population. The diagnosis of AIHA is usually associated with HD at the time of initial presentation or during the course of disease, but it could precede it by years to months. In adults the association of AIHA and HD is more frequent in advanced stages and in the nodular sclerosis and mixed cellularity type HD. Warm immune hemolytic anemia is mainly controlled with steroids and chemotherapy. We report a case of a pediatric patient with direct antiglobulin positive test at the diagnosis of a late relapse of stage III B mixed cellularity type HD. PMID:26904342

  20. Nuclear receptor and target gene mRNA abundance in duodenum and colon of dogs with chronic enteropathies.

    PubMed

    Greger, D L; Gropp, F; Morel, C; Sauter, S; Blum, J W

    2006-11-01

    Nuclear receptors (NR), such as constitutive androstane receptor (CAR), pregnane X receptor (PXR) and peroxisome proliferator-associated receptors alpha and gamma (PPARalpha, PPARgamma) are mediators of inflammation and may be involved in inflammatory bowel disease (IBD) and food responsive diarrhea (FRD) of dogs. The present study compared mRNA abundance of NR and NR target genes [multi drug-resistance gene-1 (MDR1), multiple drug-resistance-associated proteins (MRD2, MRD3), cytochrome P450 (CYP3A12), phenol-sulfating phenol sulfotransferase (SULT1A1) and glutathione-S-transferase (GST A3-3)] in biopsies obtained from duodenum and colon of dogs with IBD and FRD and healthy control dogs (CON; n=7 per group). Upon first presentation of dogs, mRNA levels of PPARalpha, PPARgamma, CAR, PXR and RXRalpha in duodenum as well as PPARgamma, CAR, PXR and RXRalpha in colon were not different among groups (P>0.10). Although mRNA abundance of PPARalpha in colon of dogs with FRD was similar in both IBD and CON (P>0.10), PPARalpha mRNA abundance was higher in IBD than CON (P<0.05). Levels of mRNA of MDR1 in duodenum were higher in FRD than IBD (P<0.05) or CON (P<0.001). Compared with CON, abundances of mRNA for MRP2, CYP3A12 and SULT1A1 were higher in both FRD and IBD than CON (P<0.05). Differences in mRNA levels of PPARalpha and MRP2 in colon and MDR1, MRP2, CYP3A12 and SULT1A1 in duodenum may be indicative for enteropathy in FRD and (or) IBD dogs relative to healthy dogs. More importantly, increased expression of MDR1 in FRD relative to IBD in duodenum may be a useful diagnostic marker to distinguish dogs with FRD from dogs with IBD. PMID:16446074

  1. Low Vitamin D Status Is Associated with Systemic and Gastrointestinal Inflammation in Dogs with a Chronic Enteropathy

    PubMed Central

    Titmarsh, Helen F.; Gow, Adam G.; Kilpatrick, Scott; Cartwright, Jennifer A.; Milne, Elspeth M.; Philbey, Adrian W.; Berry, Jacqueline; Handel, Ian; Mellanby, Richard J.

    2015-01-01

    Introduction Vitamin D deficiency, as assessed by serum concentrations of 25 hydroxyvitamin D (25(OH)D), has been linked to the development of over-zealous and inappropriate inflammation in humans. However, the relationship between vitamin D status and inflammation in dogs is ill-defined. Chronic enteropathies (CE) are frequently diagnosed in client owned dogs, have a wide range of serum 25(OH)D concentrations, and represent a spontaneous model in which to probe the relationship between vitamin D and inflammation. The hypothesis of this study was that vitamin D status would be negatively associated with systemic and gastrointestinal inflammation in dogs with a CE. The aim of this study was to examine the relationship between serum 25(OH)D concentrations and markers of systemic and gastrointestinal inflammation in a cohort of dogs with CE. Methods and Materials Serum 25(OH)D concentrations, together with neutrophil, monocyte, eosinophil and lymphocyte counts, duodenal histopathology scores, serum IL-2, IL-6, IL-8 and TNFα concentrations and were measured in 39 dogs with histologically confirmed CE. A linear regression model examined the relationship between serum 25(OH)D status and measures of inflammation. Results Serum 25(OH)D concentrations were negatively associated with neutrophil and monocyte counts, duodenal histopathology scores and serum IL-2 and IL-8 concentrations. Dogs with low serum 25(OH)D concentrations typically had an inflammatory signature characterised by high monocyte and neutrophil numbers together with low lymphocyte numbers. There is a need to establish whether low vitamin D status is a cause or consequence of inflammation. PMID:26333093

  2. Comparison of the expression, activity, and fecal concentration of intestinal alkaline phosphatase between healthy dogs and dogs with chronic enteropathy.

    PubMed

    Ide, Kaori; Kato, Kazuki; Sawa, Yuki; Hayashi, Akiko; Takizawa, Rei; Nishifuji, Koji

    2016-07-01

    OBJECTIVE To compare expression, activity, and fecal concentration of intestinal alkaline phosphatase (IAP) between healthy dogs and dogs with chronic enteropathy (CE). ANIMALS 9 healthy university-owned Beagles and 109 healthy client-owned dogs (controls) and 28 dogs with CE (cases). PROCEDURES Cases were defined as dogs with persistent (> 3 weeks) gastrointestinal signs that failed to respond to antimicrobials and anti-inflammatory doses of prednisolone or dietary trials, did not have mechanical gastrointestinal abnormalities as determined by abdominal radiography and ultrasonography, and had a diagnosis of lymphoplasmacytic enteritis or eosinophilic gastroenteritis on histologic examination of biopsy specimens. Duodenal and colonic mucosa biopsy specimens were obtained from the 9 university-owned Beagles and all cases for histologic examination and determination of IAP expression (by real-time quantitative PCR assay) and activity (by enzyme histochemical analysis). Fecal samples were obtained from all dogs for determination of fecal IAP concentration by a quantitative enzyme reaction assay. RESULTS For dogs evaluated, IAP expression and activity were localized at the luminal side of epithelial cells in the mucosa and intestinal crypts, although both were greater in the duodenum than in the colon. Active IAP was detected in the feces of all dogs. Intestinal alkaline phosphatase expression and activity were lower for cases than for controls, and fecal IAP concentration for dogs with moderate and severe CE was lower than that for dogs with mild CE. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dogs with CE had impaired IAP expression and activity. Additional research is necessary to elucidate the role of IAP in the pathogenesis of CE. PMID:27347825

  3. Zinc deficiency in children with environmental enteropathy-development of new strategies: report from an expert workshop.

    PubMed

    Young, Graeme P; Mortimer, Elissa K; Gopalsamy, Geetha L; Alpers, David H; Binder, Henry J; Manary, Mark J; Ramakrishna, Balakrishnan S; Brown, Ian L; Brewer, Thomas G

    2014-10-01

    Zinc deficiency is a major cause of childhood morbidity and mortality. The WHO/UNICEF strategy for zinc supplementation as adjunctive therapy for diarrhea is poorly implemented. A conference of experts in zinc nutrition and gastrointestinal disorders was convened to consider approaches that might complement the current recommendation and what research was needed to develop these approaches. Several key points were identified. The design of novel zinc interventions would be facilitated by a better understanding of how disturbed gut function, such as environmental (or tropical) enteropathy, affects zinc absorption, losses, and homeostasis. Because only 10% of zinc stores are able to be rapidly turned over, and appear to be rapidly depleted by acute intestinal illness, they are probably best maintained by complementary regular supplementation in a primary prevention strategy rather than secondary prevention triggered by acute diarrhea. The assessment of zinc status is challenging and complex without simple, validated measures to facilitate field testing of novel interventions. Zinc bioavailability may be a crucial factor in the success of primary prevention strategies, and a range of options, all still inadequately explored, might be valuable in improving zinc nutrition. Some therapeutic actions of zinc on diarrhea seem attributable to pharmacologic effects, whereas others are related to the reversal of deficiency (ie, nutritional). The distinction between these 2 mechanisms cannot be clarified given the insensitivity of serum zinc to identify subclinical deficiency states. Why zinc seems to be less effective than expected at all ages, and ineffective for secondary prevention of diarrhea in children <12 mo of age, remains unclear. It was concluded that a reframing of the current recommendation is warranted with consideration of how to better optimize and deliver zinc and whether to provide a complementary public health primary prevention zinc strategy. This requires

  4. Induction of autoimmune disease by deletion of CTLA-4 in mice in adulthood.

    PubMed

    Klocke, Katrin; Sakaguchi, Shimon; Holmdahl, Rikard; Wing, Kajsa

    2016-04-26

    Cytotoxic T lymphocyte antigen-4 (CTLA-4) is essential for immunological (self-) tolerance, but due to the early fatality of CTLA-4 KO mice, its specific function in central and peripheral tolerance and in different systemic diseases remains to be determined. Here, we further examined the role of CTLA-4 by abrogating CTLA-4 expression in adult mice and compared the resulting autoimmunity that follows with that produced by congenital CTLA-4 deficiency. We found that conditional deletion of CTLA-4 in adult mice resulted in spontaneous lymphoproliferation, hypergammaglobulinemia, and histologically evident pneumonitis, gastritis, insulitis, and sialadenitis, accompanied by organ-specific autoantibodies. However, in contrast to congenital deficiency, this was not fatal. CTLA-4 deletion induced preferential expansion of CD4(+)Foxp3(+) Treg cells. However, T cells from CTLA-4-deficient inducible KO mice were able to adoptively transfer the diseases into T cell-deficient mice. Notably, cell transfer of thymocytes de novo produced myocarditis, otherwise not observed in donor mice depleted in adulthood. Moreover, CTLA-4 deletion in adult mice had opposing impacts on induced autoimmune models. Thus, although CTLA-4-deficient mice had more severe collagen-induced arthritis (CIA), they were protected against peptide-induced experimental autoimmune encephalomyelitis (EAE); however, onset of protein-induced EAE was only delayed. Collectively, this indicates that CTLA-4 deficiency affects both central and peripheral tolerance and Treg cell-mediated suppression. PMID:27071130

  5. Autoimmune Myocarditis, Valvulitis, and Cardiomyopathy

    PubMed Central

    Myers, Jennifer M.; Cunningham, Madeleine W.; Fairweather, DeLisa; Huber, Sally A.

    2013-01-01

    Cardiac myosin-induced autoimmune myocarditis (EAM) is a model of inflammatory heart disease initiated by CD4+ T cells (Smith and Allen 1991; Li, Heuser et al. 2004). It is a paradigm of the immune-mediated cardiac damage believed to play a role in the pathogenesis of a subset of postinfectious human cardiomyopathies (Rose, Herskowitz et al. 1993). Myocarditis is induced in susceptible mice by immunization with purified cardiac myosin (Neu, Rose et al. 1987) or specific peptides derived from cardiac myosin (Donermeyer, Beisel et al. 1995; Pummerer, Luze et al. 1996) (see Basic Protocol 1), or by adoptive transfer of myosin-reactive T cells (Smith and Allen 1991) (see Alternate Protocol). Myocarditis has been induced in Lewis rats by immunization with purified rat or porcine cardiac myosin (Kodama, Matsumoto et al. 1990; Li, Heuser et al. 2004) (see Basic Protocol 2) or S2-16 peptide (Li, Heuser et al. 2004), or by adoptive transfer of T cells stimulated by specific peptides derived from cardiac myosin (Wegmann, Zhao et al. 1994). Myocarditis begins 12 to 14 days after the first immunization, and is maximal after 21 days. Other animal models commonly used to study myocarditis development include the pathogen-induced models in which disease is initiated by viral infection. The first murine model of acute viral myocarditis causes sudden death via viral damage to cardiomyocytes (Huber, Gauntt et al. 1998; Horwitz, La Cava et al. 2000; Fong 2003; Fuse, Chan et al. 2005; Fairweather and Rose 2007; Cihakova and Rose 2008) whereas the second model is based on inoculation with heart-passaged coxsackievirus B3 (CVB3) that includes damaged heart proteins (Fairweather, Frisancho-Kiss et al. 2004; Fairweather D 2004; Fairweather and Rose 2007; Cihakova and Rose 2008) In addition to the protocols used to induce EAM in mice and rats, support protocols are included for preparing purified cardiac myosin using mouse or rat heart tissue (see Support Protocol 1), preparing purified

  6. Understanding autoimmunity: The ion channel perspective.

    PubMed

    RamaKrishnan, Anantha Maharasi; Sankaranarayanan, Kavitha

    2016-07-01

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

  7. Macrophage activation syndrome in autoimmune disease.

    PubMed

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

    2010-01-01

    Macrophage activation syndrome (MAS) is a phenomenon characterized by cytopenia, organ dysfunction, and coagulopathy associated with an inappropriate activation of macrophages. Current diagnostic criteria are imprecise, but the syndrome is now recognized as a form of hemophagocytic lymphohistiocytosis that is characteristically associated with autoimmune diatheses. The diagnosis of incipient MAS in patients with autoimmune disease requires a high index of suspicion, as several characteristics of the disorder may be present in the underlying condition or infectious complications associated with the treatment thereof. Proposed treatment regimens include aggressive approaches that require validation in future controlled studies. This review discusses the major aspects of the pathophysiology, diagnosis, and management of MAS with a focus on the association with autoimmune disease. PMID:20407267

  8. Immunogenetics of autoimmune diseases in Asian Indians.

    PubMed

    Mehra, N K; Kaur, Gurvinder; Kanga, Uma; Tandon, Nikhil

    2002-04-01

    The HLA class II molecules play a critical role in the processing and presentation of specific peptides derived from autoantigens of pancreatic beta cells or gluten for T cell scrutiny in IDDM and CD. In the present study, extended DR3-positive haplotypes associated with autoimmunity in northern Indian patients have been reported. The haplotype A26-B8-DR3 was the most common autoimmunity-favoring haplotype encountered among these patients. This association is, indeed, unique to Indian autoimmune patients, as it replaces the otherwise most commonly associated Caucasian haplotype A1-B8-DR3 (AH8.1) in this population. Further, CD patients revealed 100% association with DQB1*0201 along with DQA*0501 (97%) either in cis or trans configuration. PMID:12021136

  9. Pregnancy and autoimmune connective tissue diseases.

    PubMed

    Marder, Wendy; Littlejohn, Emily A; Somers, Emily C

    2016-02-01

    Autoimmune connective tissue diseases predominantly affect women and often occur during the reproductive years. Thus, specialized issues in pregnancy planning and management are commonly encountered in this patient population. This chapter provides a current overview of pregnancy as a risk factor for onset of autoimmune disease, considerations related to the course of pregnancy in several autoimmune connective tissue diseases, and disease management and medication issues before pregnancy, during pregnancy, and in the postpartum period. A major theme that has emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and that maternal and fetal health can be optimized when conception is planned during times of inactive disease and through maintaining treatment regimens compatible with pregnancy. PMID:27421217

  10. Epidemiology of Autoimmune Diseases in Denmark

    PubMed Central

    Eaton, William W.; Rose, Noel R.; Kalaydjian, Amanda; Pedersen, Marianne G.; Mortensen, Preben Bo

    2007-01-01

    An epidemiologic study of the autoimmune diseases taken together has not been done heretofore. The National Patient Register of Denmark is used to estimate population prevalence of 31 possible or probable autoimmune diseases. Record linkage is used to estimate 465 pairwise comorbidities in individuals among the 31 diseases, and familial aggregation among sibs, parents and offspring. The prevalence of any of the 31 diseases in the population is more than 5%. Within individuals, there is extensive comorbidity across the 31 diseases. Within families, aggregation is strongest for individual diseases, and weak across diseases. These data confirm the importance of the autoimmune diseases as a group, and suggest that common etiopathologies exist among them. PMID:17582741

  11. Gq-Coupled Receptors in Autoimmunity

    PubMed Central

    Zhang, Lu; Shi, Guixiu

    2016-01-01

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

  12. [Clinical manifestations of adult celiac disease].

    PubMed

    Malamut, G; Cellier, C

    2013-06-01

    Celiac disease is an enteropathy due to gluten intake in genetically predisposed persons (HLA DQ2/DQ8). Celiac disease occurs in adults and children at rates approaching 1% of population in Europe and USA. Celiac disease is extremely various and anaemia, oral aphthous stomatis, amenorrhea or articular symptoms may be the only revealing symptoms. Diagnosis releases on evidence of histological villous atrophy in proximal small bowel and presence of specific serum antibodies. Treatment relies on eviction of gluten. Gluten free diet allows prevention of malignant complications such as small bowel adenocarcinoma and lymphoma and osteopenia. The main cause of resistance to gluten free diet is its bad observance. On the contrary, serious complications of celiac disease, such as clonal refractory celiac sprue and intestinal T-cell lymphoma need to be screen. PMID:21621928

  13. MicroRNAs in Autoimmune Diseases

    PubMed Central

    Qu, Zigang; Li, Wenhui; Fu, Baoquan

    2014-01-01

    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

  14. [Ludwig van Beethoven: an autoimmune deafness?].

    PubMed

    Davies, P J

    1995-01-01

    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

  15. Pharmacologic Therapies for Rheumatologic and Autoimmune Conditions.

    PubMed

    Bays, Alison M; Gardner, Gregory

    2016-07-01

    Disease-modifying antirheumatic drugs (DMARDs) are commonly prescribed by rheumatologists to reduce disease activity and induce remission in autoimmune conditions such as systemic lupus erythematosus and rheumatoid arthritis. Steroids are sometimes used in combination with DMARD therapy and should be used at the lowest effective dose for the least amount of time. There are many biologic agents available for use for inflammatory arthritis and other autoimmune conditions. Care should be taken when prescribing and managing DMARDS, steroids and biologic agents medications with a careful eye towards screening for infectious disease, vaccination, bone heath and lab monitoring. PMID:27235612

  16. The immunofluorescence techniques in the diagnosis of endocrine autoimmune diseases.

    PubMed

    Betterle, Corrado; Zanchetta, Renato

    2012-08-01

    In the study of autoimmune diseases, the laboratory plays a very important role. We describe the immunofluorescence techniques (direct, indirect, complement-fixing, double) for determining the presence of autoantibodies and their role in the autoimmune endocrine diseases. PMID:26000129

  17. Total Recovery from Monoclonal Gammopathy and Autoimmune Phenomena After Parathyroidectomy

    PubMed Central

    Cañas, Carlos A; Echeverri, Andrés F; Anaya, Juan-Manuel

    2012-01-01

    Based on the observation of a patient with a causal relationship between hyperparathyroidism and development of both autoimmune disease and paraproteinemia, we hypothesize a novel cause of autoimmunity triggered in the context of hyperparathyroidism. PMID:22870165

  18. Genetics Home Reference: autoimmune polyglandular syndrome, type 1

    MedlinePlus

    ... polyglandular syndrome, type 1 autoimmune polyglandular syndrome, type 1 Enable Javascript to view the expand/collapse boxes. ... All Close All Description Autoimmune polyglandular syndrome, type 1 is an inherited condition that affects many of ...

  19. Successful treatment of pediatric IgG4 related systemic disease with mycophenolate mofetil: case report and a review of the pediatric autoimmune pancreatitis literature

    PubMed Central

    2011-01-01

    Autoimmune pancreatitis is frequently associated with elevated serum and tissue IgG4 levels in the adult population, but there are few reports of pediatric autoimmune pancreatitis, and even fewer reports of IgG4 related systemic disease in a pediatric population. The standard of care treatment in adults is systemic corticosteroids with resolution of symptoms in most cases; however, multiple courses of corticosteroids are occasionally required and some patients require long term corticosteroids. In these instances, steroid sparing disease modify treatments are in demand. We describe a 13-year-old girl with IgG4 related systemic disease who presented with chronic recurrent autoimmune pancreatitis resulting in surgical intervention for obstructive hyperbilirubinemia and chronic corticosteroid treatment. In addition, she developed fibrosing medianstinitis as part of her IgG4 related systemic disease. She was eventually successfully treated with mycophenolate mofetil allowing for discontinuation of corticosteroids. This is the first reported use of mycophenolate mofetil for IgG4 related pancreatitis. Although autoimmune pancreatitis as part of IgG4 related systemic disease is rarely reported in pediatrics, autoimmune pancreatitis is also characterized as idiopathic fibrosing pancreatitis. All pediatric autoimmune pancreatitis cases reported in the world medical literature were identified via a PUBMED search and are reviewed herein. Twelve reports of pediatric autoimmune pancreatitis were identified, most of which were treated with corticosteroids or surgical approaches. Most case reports failed to report IgG4 levels, so it remains unclear how commonly IgG4 related autoimmune pancreatitis occurs during childhood. Increased evaluation of IgG4 levels in patients with autoimmune pancreatitis may shed further light on the association of IgG4 with pancreatitis and the underlying pathophysiology. PMID:21205323

  20. Therapeutic strategies for autoimmune hepatitis.

    PubMed

    Manns, Michael P; Strassburg, Christian P

    2011-01-01

    Autoimmune hepatitis (AIH) is a disease of unknown etiology. However, a loss of tolerance against the patient's own liver is regarded as the main pathogenetic mechanism. Immunosuppressive therapy prolongs survival in patients with severe AIH. Two phases of therapy have to be distinguished. In newly diagnosed AIH, induction of remission is the main goal. Here predniso(lo)ne alone or in combination with azathioprine has been shown to induce remission in the majority of patients. In the past, reduction of aminotransferase levels below two times the upper limit of normal was the aim of therapy. Nowadays, normalization of aminotransferase levels should be achieved. The majority of patients usually respond to therapy within 6-12 months. A significant reduction in aminotransferase levels is achieved within a few weeks of therapy. Improvement in clinical symptoms is followed by improvement in biochemical parameters of disease activity and then by significant improvement in histological disease activity. Around 20-40% of patients do not achieve remission. In these patients, alternative therapies should be evaluated for the individual patient. Prospective controlled trials with a larger number of patients are missing in this population. At the moment, mycophenolate mofetil at a dose of 2 × 1 g daily, either given alone or in combination with predniso(lo)ne, is able to achieve remission in a significant proportion of patients. Based on recent retrospective observations, mycophenolate mofetil is beneficial in patients who were previously azathioprine intolerant rather than azathioprine failure patients. Again, prospective trials are missing. Alternative drugs include cyclophosphamide, cyclosporin A, tacrolimus and others. Women in particular suffer from steroid-specific side effects, including weight gain, moon face, diabetes, glaucoma and bone disease. Recently, a topical steroid, budesonide, was shown to induce disease remission in combination with azathioprine. The second

  1. Presence of Idiopathic Thrombocytopenic Purpura and autoimmune hemolytic anemia in the patients with common variable immunodeficiency.

    PubMed

    Ramyar, Asghar; Aghamohammadi, Asghar; Moazzami, Kasra; Rezaei, Nima; Yeganeh, Mehdi; Cheraghi, Taher; Pouladi, Nima; Heydari, Golnaz; Abolhassani, Hassan; Amirzargar, Ali Akbar; Parvaneh, Nima; Moin, Mostafa

    2008-09-01

    Common Variable Immunodeficiency (CVID) is a heterogeneous group of disorders characterized by hypogammaglobulinemia and an increased susceptibility to recurrent infections as well as autoimmunity and malignancies. Idiopathic Thrombocytopenic Purpura (ITP) and Autoimmune Hemolytic Anemia (AIHA) are two autoimmune disorders which may be seen in association with CVID. Among 85 CVID patients, seven cases had ITP and/or AIHA (8%). Four of these patients had one or more episodes of ITP, one patient had AIHA, and two patients had both ITP and AIHA (Evans syndrome). Almost, all patients experienced chronic and recurrent infections mostly in respiratory and gastrointestinal systems during the course of the disease. Among the seven patients, five presented their underlying disease with recurrent respiratory and/or gastrointestinal tract infections, while in two remaining patients, CVID was presented with ITP. Three patients died until now; two because of hepatic failure and one due to pulmonary hemorrhage. As CVID is prone to autoimmune disorders, it should be considered as a differential diagnosis of adult-onset ITP and possibly in children. Chronic and recurrent ITP, especially in the presence of propensity to respiratory and gastrointestinal infections mandate the evaluation for an underlying immune dysregulation such as CVID. PMID:18780952

  2. Emu Oil Reduces Small Intestinal Inflammation in the Absence of Clinical Improvement in a Rat Model of Indomethacin-Induced Enteropathy

    PubMed Central

    Abimosleh, Suzanne M.; Tran, Cuong D.; Howarth, Gordon S.

    2013-01-01

    Nonsteroidal-anti-inflammatory-drug (NSAID) enteropathy is characterized by small intestinal damage and ulceration. Emu Oil (EO) has previously been reported to reduce intestinal inflammation. Aim. We investigated EO for its potential to attenuate NSAID-enteropathy in rats. Methods. Male Sprague Dawley rats (n = 10/group) were gavaged with Water, Olive Oil (OO), or EO (0.5 mL; days 0–12) and with 0.5 mL Water or the NSAID, Indomethacin (8 mg/kg; days 5–12) daily. Disease activity index (DAI), 13C-sucrose breath test (SBT), organ weights, intestinal damage severity (IDS), and myeloperoxidase (MPO) activity were assessed. P < 0.05 was considered significant. Results. In Indomethacin-treated rats, DAI was elevated (days 10–12) and SBT values (56%) and thymus weight (55%) were decreased, relative to normal controls. Indomethacin increased duodenum (68%), colon (24%), SI (48%), caecum (48%), liver (51%) and spleen (88%) weights, IDS scores, and MPO levels (jejunum: 195%, ileum: 104%) compared to normal controls. Jejunal MPO levels were decreased (64%) by both EO and OO, although only EO decreased ileal MPO (50%), compared to Indomethacin controls. Conclusions. EO reduced acute intestinal inflammation, whereas other parameters of Indomethacin-induced intestinal injury were not affected significantly. Increased EO dose and/or frequency of administration could potentially improve clinical efficacy. PMID:23573127

  3. Morphological and biochemical studies of a naturally occurring enteropathy in the Irish setter dog: a comparison with coeliac disease in man.

    PubMed

    Batt, R M; Carter, M W; McLean, L

    1984-11-01

    A naturally occurring enteropathy was identified in Irish setter dogs and wheat-sensitivity was demonstrated in a litter bred from two of the affected animals. The morphological and biochemical features of this enteropathy are described and compared to coeliac disease in man. Affected animals comprised 10 dogs that presented with poor weight gain or weight loss, with or without diarrhoea. Exocrine pancreatic function was normal and culture of duodenal juice demonstrated no marked bacterial overgrowth. Serum vitamin B12 concentrations were unaltered, but in some cases low serum and erythrocyte folate concentrations and reduced xylose absorption provided indirect evidence for proximal small intestinal disease. Examination of peroral jejunal biopsies revealed patchy morphological changes within individual animals, comprising predominantly partial, but in one case subtotal, villous atrophy. Brush border enzymes were selectively altered: the specific activities of alkaline phosphatase, leucyl-2-naphthylamidase and of zinc-resistant alpha-glucosidase were reduced by approximately 40 per cent, while activities of maltase, sucrase, lactase and gamma-glutamyl transferase were unaltered. Activity of a lysosomal enzyme was increased and there was evidence for enhanced lysosomal fragility. The activity of malate dehydrogenase, with a dual mitochondrial and cytoplasmic localisation, was decreased but there were no changes in the activities of marker enzymes for basal-lateral membranes, endoplasmic reticulum or peroxisomes. These findings, particularly the specific biochemical abnormalities, were comparable to those in partially treated coeliac disease in man; however, a specific role for wheat in the pathogenesis of the disease has yet to be defined. PMID:6522828

  4. Requirements for innate immune pathways in environmentally induced autoimmunity.

    PubMed

    Pollard, Kenneth Michael; Kono, Dwight H

    2013-01-01

    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-κB-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

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

    PubMed Central

    2010-01-01

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

  6. Scurfy mice: A model for autoimmune disease

    SciTech Connect

    Godfrey, V.L.

    1993-01-01

    Autoimmune disease-the condition in which the body attacks its own tissue-has been an object of public concern recently. Former President George Bush and his wife Barbara both are afflicted with Graves' disease in which the body's own immune system attakcs the thyroid gland. The safety of breast implants was called into question because of evidence that some recipients had developed autoimmune disorders such a rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Women, the media pointed out, have a higher-than-average incidence of many autoimmune disorders. These events suggest the need to know more about what makes the immune system work so well and what makes it go awry. At ORNL's Biology Division, progress is being in understanding the underlying causes of immune disease by studying mice having a disease that causes them to be underdeveloped; to have scaly skin, small ears, and large spleens; to open their eyes late; and to die early. These [open quotes]scurfy[close quotes]mice are helping us better understand the role of the thymus gland in autoimmune disease.

  7. Pediatric autoimmune neuropsychiatric disorders after streptococcus infection.

    PubMed

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

    2012-10-01

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

  8. [Autoimmune hepatitis and overlap syndrome: therapy].

    PubMed

    Löhr, H F

    2002-08-21

    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

  9. Autism and Autoimmune Disease: A Family Study

    ERIC Educational Resources Information Center

    Money, John; And Others

    1971-01-01

    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)

  10. Oral mucosal manifestations of autoimmune skin diseases.

    PubMed

    Mustafa, Mayson B; Porter, Stephen R; Smoller, Bruce R; Sitaru, Cassian

    2015-10-01

    A group of autoimmune diseases is characterised by autoantibodies against epithelial adhesion structures and/or tissue-tropic lymphocytes driving inflammatory processes resulting in specific pathology at the mucosal surfaces and the skin. The most frequent site of mucosal involvement in autoimmune diseases is the oral cavity. Broadly, these diseases include conditions affecting the cell-cell adhesion causing intra-epithelial blistering and those where autoantibodies or infiltration lymphocytes cause a loss of cell-matrix adhesion or interface inflammation. Clinically, patients present with blistering, erosions and ulcers that may affect the skin as well as further mucosal surfaces of the eyes, nose and genitalia. While the autoimmune disease may be suspected based on clinical manifestations, demonstration of tissue-bound and circulating autoantibodies, or lymphocytic infiltrates, by various methods including histological examination, direct and indirect immunofluorescence microscopy, immunoblotting and quantitative immunoassay is a prerequisite for definitive diagnosis. Given the frequency of oral involvement and the fact that oral mucosa is the initially affected site in many cases, the informed practitioner should be well acquainted with diagnostic and therapeutic aspects of autoimmune dermatosis with oral involvement. This paper reviews the pathogenesis and clinical presentation of these conditions in the oral cavity with a specific emphasis on their differential diagnosis and current management approaches. PMID:26117595

  11. Follicular Helper T Cells in Autoimmunity.

    PubMed

    Scherm, Martin G; Ott, Verena B; Daniel, Carolin

    2016-08-01

    The development of multiple disease-relevant autoantibodies is a hallmark of autoimmune diseases. In autoimmune type 1 diabetes (T1D), a variable time frame of autoimmunity precedes the clinically overt disease. The relevance of T follicular helper (TFH) cells for the immune system is increasingly recognized. Their pivotal contribution to antibody production by providing help to germinal center (GC) B cells facilitates the development of a long-lived humoral immunity. Their complex differentiation process, involving various stages and factors like B cell lymphoma 6 (Bcl6), is strictly controlled, as anomalous regulation of TFH cells is connected with immunopathologies. While the adverse effects of a TFH cell-related insufficient humoral immunity are obvious, the role of increased TFH frequencies in autoimmune diseases like T1D is currently highlighted. High levels of autoantigen trigger an excessive induction of TFH cells, consequently resulting in the production of autoantibodies. Therefore, TFH cells might provide promising approaches for novel therapeutic strategies. PMID:27324759

  12. CNS autoimmune inflammation: RICK must NOD!

    PubMed

    Kang, Zizhen; Gulen, Muhammet Fatih; Li, Xiaoxia

    2011-01-28

    In this issue of Immunity, Shaw et al. (2011) report that the NOD-RICK signaling axis is required for the activation of dendritic cells infiltrating the central nervous system, leading to reactivation of antigen-specific T cells and autoimmune inflammation. PMID:21272781

  13. Imaging combined autoimmune and infectious disease microarrays

    NASA Astrophysics Data System (ADS)

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

    2006-09-01

    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

  14. Autoimmune hepatitis. Definition--classification--histopathology--immunopathogenesis.

    PubMed

    Meyer zum Büschenfelde, K H; Dienes, H P

    1996-09-01

    Autoimmune hepatitis (AIH) is a distinct form of acute and chronic inflammatory liver disease in which immune reactions against host antigens are found to be the major pathological mechanism. If left untreated it carries an unfavourable prognosis, and the diagnosis should be made as soon as possible. The diagnostic approach has been greatly facilitated by the establishment of a panel of marker autoantibodies, which do not define distinct therapeutic groups of AIH, but do allow a subgrouping based on differences in patient populations, some clinical features and prognosis. The characterization of organ-specific components of the liver cell surface as targets of cellular and humoral autoimmune reactions give new insights into the pathogenesis of the disease, even though the primary event triggering the disease remains to be defined. The most important disease-promoting factor seems to be a genetically determined background for autoimmunity. Without this different environmental factors, including viruses, toxins, cytokines and drugs, are only able to induce transient autoimmune phenomena and not autoimmune disease. The histopathology of AIH is in keeping with the present pathogenetic concept. Although there is no pathognomonic feature distinguishing this type of hepatitis from virus-induced forms, some distinct morphological lesions are regarded as characteristic. Clinical research on AIH has benefited greatly from observations of experimental AIH in mice. Recognition of the critical role of autoreactive T-lymphocytes in the pathogenesis and the observation of spontaneous recovery from AIH in the animal model associated with antigen-specific and antigen-non-specific T-cell suppression have made basic contributions to our improved understanding of the natural course of AIH in humans. PMID:8865847

  15. Inflammasomes and human autoimmunity: A comprehensive review.

    PubMed

    Yang, Chin-An; Chiang, Bor-Luen

    2015-07-01

    Inflammasomes are multi-protein complexes composed of a NOD-like receptor (NLR)/an AIM-like receptor (ALR), the adapter molecule apoptosis-associated speck-like protein that contains a CARD (ASC), and caspase-1. Active caspase-1 cleaves pro-IL-1β and pro-IL-18 to IL-1β and IL-18, resulting in inflammation. Genetic mutations in inflammasomes were first recognized to result in autoinflammatory diseases, which are characterized by the absence of both autoantibodies and autoreactive-T/B cells. However, there is increasing attention being placed on genetic polymorphisms that are involved in the components of inflammasomes, and these have implications for innate immunity and the natural history of autoimmune diseases. For example, while the NOD-like receptor family, pyrin domain containing 1 (NLRP1) haplotypes contributes to susceptibility to developing vitiligo; there are other single nucleotide polymorphisms (SNPs) that alters the susceptibility and severity of rheumatoid arthritis (RA) and juvenile idiopathic arthritis. Indeed, there are multiple factors that contribute to lowering the threshold of immunity and inflammasomes play a key role in this threshold. For example, IL-1β and IL-18 further perpetuate Th17 responses and endothelial cell damage, which potentiate a number of autoimmune diseases, including synovitis in RA, cardiovascular disease, and systemic lupus erythematosus (SLE). There is also increasing data on the role of innate immunity in experimental autoimmune encephalomyelitis (EAE), in lupus nephritis, and in a variety of autoimmune pathologies in which activation of the innate immune system is the driver for the adaptive system. Indeed, it is likely that the chronic pathology of autoimmunity is mediated in part by otherwise innocent bystander cells, augmented by inflammasomes. PMID:26005048

  16. Nutritional profile of adult patients with celiac disease.

    PubMed

    Abenavoli, L; Delibasic, M; Peta, V; Turkulov, V; De Lorenzo, A; Medić-Stojanoska, M

    2015-11-01

    Celiac disease (CD) is a chronic immune-mediated gluten dependent enteropathy induced by ingestion of gluten, characterized by intestinal malabsorption and subtotals or total atrophy of intestinal villi. The predominant consequence of CD in untreated patients, is malnutrition as a result of malabsorption. Moreover, several and increasing extra-intestinal clinical manifestations have been described in the CD patients. Strict adherence to a gluten-free diet (GFD) improves nutritional status, inducing an increase in fat and bone compartments, but does not completely normalize body composition and nutritional deficiencies. An early and accurate evaluation of nutritional status can be of the pivotal step in the clinical management of the adult CD patients. The aim of this review is to present the most important and recent data on nutritional and metabolic features in the CD adult patients, the related implications and the effects of the GFD on these conditions. PMID:26636515

  17. Helicobacter pylori and autoimmune disease: Cause or bystander

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-12-01

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

  19. Dilemmas in autoimmune pancreatitis. Surgical resection or not?

    PubMed

    Hoffmanova, I; Gurlich, R; Janik, V; Szabo, A; Vernerova, Z

    2016-01-01

    Surgical treatment is not commonly recommended in the management of autoimmune pancreatitis. The article describes a dilemma in diagnostics and treatment of a 68-year old man with the mass in the head of the pancreas that mimicked pancreatic cancer and that was diagnosed as a type 1 autoimmune pancreatitis (IgG4-related pancreatitis) after a surgical resection. Diagnosis of the autoimmune pancreatitis is a real clinical challenge, as in the current diagnostic criteria exists some degree of overlap in the findings between autoimmune pancreatitis and pancreatic cancer (indicated by the similarity in radiologic findings, elevation of IgG4, sampling errors in pancreatic biopsy, and the possibility of synchronous autoimmune pancreatitis and pancreatic cancer). Despite the generally accepted corticosteroids as the primary treatment modality in autoimmune pancreatitis, we believe that surgical resection remains necessary in a specific subgroup of patients with autoimmune pancreatitis (Fig. 4, Ref. 37). PMID:27546699

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

    PubMed Central

    Greer, Judith M; McCombe, Pamela A

    2012-01-01

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

  1. Classification and therapeutic approaches in autoimmune hemolytic anemia: an update.

    PubMed

    Michel, Marc

    2011-12-01

    Autoimmune hemolytic anemia (AIHA) is an uncommon autoantibody-mediated immune disorder that affects both children and adults. The diagnosis of AIHA relies mainly on the direct antiglobulin test, which is a highly sensitive and relatively specific test. The classification of AIHA is based on the pattern of the direct antiglobulin test and on the immunochemical properties of the autoantibody (warm or cold type), but also on the presence or absence of an underlying condition or disease (secondary vs primary AIHAs) that may have an impact on treatment and outcome. The distinction between AIHAs due to warm antibody (wAIHA) and AIHAs due to cold antibody is a crucial step of the diagnostic procedure as it influences the therapeutic strategy. Whereas corticosteroids are the cornerstone of treatment in wAIHA, they have no or little efficacy in cold AIHA. In wAIHA that is refractory or dependent to corticosteroids, splenectomy and rituximab are both good alternatives and the benefit?risk ratio of each option must be discussed on an individual basis. In chronic agglutinin disease, the most common variety of cold AIHA in adults, beyond supportive measures, rituximab given either alone or in combination with chemotherapy may be helpful. In this article, the classification of AIHA and the recent progress in therapeutics are discussed. PMID:22077525

  2. Etanercept (SB4): A Review in Autoimmune Inflammatory Diseases.

    PubMed

    Burness, Celeste B; Duggan, Sean T

    2016-08-01

    Etanercept (SB4) [Benepali(®)], a tumour necrosis factor inhibitor that is a biosimilar of reference etanercept (Enbrel(®)), is approved in the EU for use in all adult indications for which reference etanercept is approved, namely rheumatoid arthritis, axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis), psoriatic arthritis, and plaque psoriasis. The approval of etanercept (SB4) was based on the results of stringent comparability exercises designed to demonstrate similarity to reference etanercept in terms of quality, biological activity, efficacy, safety, and immunogenicity. In two well-designed clinical trials, etanercept (SB4) was equivalent to reference etanercept with regard to pharmacokinetic properties in healthy volunteers and in terms of efficacy in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy. Longer-term efficacy (up to 52 weeks) was also similar in both treatment groups. Etanercept (SB4) was generally well tolerated, with a similar safety profile to that of reference etanercept. Preliminary results of the open-label extension period (100 weeks) suggest that transitioning from reference etanercept to etanercept (SB4) was associated with sustained efficacy and no change in the adverse event profile or immunogenicity. In conclusion, etanercept (SB4) provides therapeutically equivalent alternative in adult patients with autoimmune inflammatory diseases requiring treatment with etanercept. PMID:27455991

  3. The neonatal CNS is not conducive for encephalitogenic Th1 T cells and B cells during experimental autoimmune encephalomyelitis

    PubMed Central

    2013-01-01

    Multiple sclerosis (MS) is thought to be a CD4+ T cell mediated autoimmune demyelinating disease of the central nervous system (CNS) that is rarely diagnosed during infancy. Cellular and molecular mechanisms that confer disease resistance in this age group are unknown. We tested the hypothesis that a differential composition of immune cells within the CNS modulates age-associated susceptibility to CNS autoimmune disease. C57BL/6 mice younger than eight weeks were resistant to experimental autoimmune encephalomyelitis (EAE) following active immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (p) 35–55. Neonates also developed milder EAE after transfer of adult encephalitogenic T cells primed by adult or neonate antigen presenting cells (APC). There was a significant increase in CD45+ hematopoietic immune cells and CD45+ high side scatter granulocytes in the CNS of adults, but not in neonates. Within the CD45+ immune cell compartment of adults, the accumulation of CD4+ T cells, Gr-1+ and Gr-1- monocytes and CD11c+ dendritic cells (DC) was identified. A significantly greater percentage of CD19+ B cells in the adult CNS expressed MHC II than neonate CNS B cells. Only in the adult CNS could IFNγ transcripts be detected 10 days post immunization for EAE. IFNγ is highly expressed by adult donor CD4+ T cells that are adoptively transferred but not by transferred neonate donor cells. In contrast, IL-17 transcripts could not be detected in adult or neonate CNS in this EAE model, and neither adult nor neonate donor CD4+ T cells expressed IL-17 at the time of adoptive transfer. PMID:23705890

  4. Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party.

    PubMed

    Daikeler, Thomas; Labopin, Myriam; Di Gioia, Massimo; Abinun, Mario; Alexander, Tobias; Miniati, Irene; Gualandi, Francesca; Fassas, Athanasios; Martin, Thierry; Schwarze, Carl Philipp; Wulffraat, Nico; Buch, Maya; Sampol, Antonia; Carreras, Enric; Dubois, Benedicte; Gruhn, Bernd; Güngör, Tayfun; Pohlreich, David; Schuerwegh, Annemie; Snarski, Emilian; Snowden, John; Veys, Paul; Fasth, Anders; Lenhoff, Stig; Messina, Chiara; Voswinkel, Jan; Badoglio, Manuela; Henes, Jörg; Launay, David; Tyndall, Alan; Gluckman, Eliane; Farge, Dominique

    2011-08-11

    To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34(+) graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT. PMID:21596847

  5. Targeting Syk in Autoimmune Rheumatic Diseases

    PubMed Central

    Deng, Guo-Min; Kyttaris, Vasileios C.; Tsokos, George C.

    2016-01-01

    Spleen tyrosine kinase (Syk) is a member of the Src family of non-receptor tyrosine kinases, which associates directly with surface receptors, including B-cell receptor and Fcγ receptor, and is involved in a variety of signal transduction pathways. Rheumatoid arthritis (RA) and systemic lupus erythematosus are autoimmune diseases in which autoantibodies, immune complexes, and autoreactive T cells account for the expression of tissue inflammation and damage. Syk inhibitors efficiently suppress RA in patients albeit in the expression of unwanted side effects, including gastrointestinal effects, hypertension, and neutropenia. Syk inhibitors also inhibit clinical manifestations in lupus-prone mice. Here, we review the evidence that supports the use of Syk inhibitors to treat rheumatic and other autoimmune diseases. PMID:27014261

  6. Is Tourette's syndrome an autoimmune disease?

    PubMed

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

    2002-01-01

    We provide a review of recent research findings which support the involvement of autoimmunity in childhood-onset tic disorders, in particular the presence of antineuronal autoantibodies, D8/17 B lymphocyte overexpression, a marker of chorea associated with streptococcal infection, and possible beneficial effects of immunomodulatory intervention. One of the most controversial areas in this field is the validity of the proposed PANDAS concept. Some researchers have delineated a putatively unique subgroup of patients, from the spectrum of illness encompassing Tourette's syndrome and obsessive-compulsive disorder (OCD), whose tics and obsessive-compulsive symptoms are shown to arise in response to beta-hemolytic streptococcal infections. They designated it by the term pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Herein we additionally present pros and cons concerning the concept of PANDAS. Finally, recommendations for future research directions are given. PMID:12082557

  7. Neuromyelitis optica (NMO) and autoimmune thyroiditis.

    PubMed

    Sudulagunta, Sreenivasa Rao; Sodalagunta, Mahesh Babu; Khorram, Hadi; Sepehrar, Mona; Aheta Sham, Mohammed; Nidsale Sudarshan, Ranjitha; Gangadharappa, Rekha

    2015-10-01

    Neuromyelitis optica (NMO or Devic's syndrome) is a rare demyelinating disease of the CNS that predominantly affects the spinal cord and optic nerves and shares many clinical and radiological features with multiple sclerosis (MS). The association of NMO with autoimmune thyroiditis has been reported very rarely. Early differentiation between NMO and MS is very important because they have different natural courses and treatment regimens. We report a case regarding a 53-year-old woman who was admitted initially with hiccups and paraesthesias, but was not evaluated during first two episodes and presented with severe progression of NMO. Patient was found to have autoimmune thyroiditis with lymphocytic infiltration of thyroid which progressed to hypothyroidism. NMO was diagnosed with seropositivity for NMO-IgG and longitudinally extensive spinal cord lesions (three or more spinal segments). Patient poorly responded to treatment due to the lack of early diagnosis and aggressive immunosuppressant therapy. PMID:26568836

  8. Autoimmune lymphoproliferative syndrome presenting with glomerulonephritis.

    PubMed

    Kanegane, Hirokazu; Vilela, Maria Marluce dos Santos; Wang, Yue; Futatani, Takeshi; Matsukura, Hiroyoshi; Miyawaki, Toshio

    2003-05-01

    Autoimmune lymphoproliferative syndrome (ALPS) is characterized clinically by chronic non-malignant lymphoproliferation and autoimmunity and is caused by a genetic defect in programmed cell death (apoptosis). Most patients with ALPS have heterozygous mutations in the Fas gene. We describe an 11-year-old Brazilian boy with hepatosplenomegaly, lymphadenopathy, hemolytic anemia, and hypergammaglobulinemia since early infancy. T cell lines from the patient were defective in Fas-mediated apoptosis. He was diagnosed as having ALPS and found to have a novel Fas gene mutation (IVS4+1G>A). In addition, he presented with glomerulonephritis in infancy. An aunt and uncle who had the same Fas mutations also had histories of glomerulonephritis. Although glomerulonephritis is common in Fas-deficient mice, it is infrequent in human ALPS. Corticosteroid therapy ameliorated the glomerulonephritis in our patient, as well as his lymphoproliferation, anemia, and hypergammaglobulinemia. This study suggests that glomerulonephritis is one of the characteristic features of ALPS. PMID:12736807

  9. Fetal microchimeric cells in autoimmune thyroid diseases

    PubMed Central

    Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter

    2013-01-01

    Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD. PMID:23723083

  10. [Biochemical and immunological markers of autoimmune thyroiditis].

    PubMed

    Biktagirova, E M; Sattarova, L I; Vagapova, G R; Skibo, Y V; Chuhlovina, E N; Kravtsova, O A; Abramova, Z I

    2016-05-01

    Correlations between biochemical and immunological markers of programmed cell death (apoptosis), and the functional state of the thyroid gland (hyperthyroidism, euthyroidism, hypothyroidism) have been investigated in autoimmune thyroiditis (AT) (also known as chronic autoimmune thyroiditis). Annexin V, TRAIL and TNF-a, as well as DNA-hydrolyzing antibodies were used as the main markers. Increased levels of TRAIL were found in the serum of AT patients (hyperthyroidism>hypothyroidism>euthyroidism) compared with healthy individuals. The highest frequency of antibodies to denatured DNA (Abs-dDNA) had the highest frequency in AT patients (97%) compared with healthy controls. Among these patients, 75% had hyperthyroidism, 85% had hypothyroidism, and 84.7% had euthyroidism. Abs hydrolyzing activity demonstrated correlation dependence with symptoms of the thyroid dysfunction. PMID:27563001

  11. Autoimmune Myopathies: Where Do We Stand?

    PubMed Central

    Simon, Jean-Philippe; Marie, Isabelle; Jouen, Fabienne; Boyer, Olivier; Martinet, Jérémie

    2016-01-01

    Autoimmune diseases (AIDs) as a whole represent a major health concern and remain a medical and scientific challenge. Some of them, such as multiple sclerosis or type 1 diabetes, have been actively investigated for many decades. Autoimmune myopathies (AIMs), also referred to as idiopathic inflammatory myopathies or myositis, represent a group of very severe AID for which we have a more limited pathophysiological knowledge. AIM encompass a group of, individually rare but collectively not so uncommon, diseases characterized by symmetrical proximal muscle weakness, increased serum muscle enzymes such as creatine kinase, myopathic changes on electromyography, and several typical histological patterns on muscle biopsy, including the presence of inflammatory cell infiltrates in muscle tissue. Importantly, some AIMs are strongly related to cancer. Here, we review the current knowledge on the most prevalent forms of AIM and, notably, the diagnostic contribution of autoantibodies. PMID:27379096

  12. Autoimmunity vs. cancer: predator vs. alien?

    PubMed

    Berens, Christian; Lauber, Kirsten; Herrmann, Martin

    2013-08-01

    "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

  13. [Glycosylation of autoantibodies in autoimmunes diseases].

    PubMed

    Goulabchand, R; Batteux, F; Guilpain, P

    2013-12-01

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

  14. Fibrosis in autoimmune and cholestatic liver disease.

    PubMed

    Penz-Österreicher, Melitta; Österreicher, Christoph H; Trauner, Michael

    2011-04-01

    Autoimmune and cholestatic liver disease account for a significant part of end-stage liver disease and are leading indications for liver transplantation. Especially cholestatic liver diseases (primary biliary cirrhosis and primary sclerosing cholangitis) appear to be different from other chronic liver diseases with regards to pathogenesis. Portal fibroblasts located in the connective tissue surrounding bile ducts appear to be different from hepatic stellate cells with regards to expression of marker proteins and response the profibrogenic and mitogenic stimuli. In addition there is increasing evidence for a cross talk between activated cholangiocytes and portal myofibroblasts. Several animal models have improved our understanding of the mechanisms underlying these chronic liver diseases. In the present review, we discuss the current concepts and ideas with regards to myofibroblastic cell populations, mechanisms of fibrosis, summarize characteristic histological findings and currently employed animal models of autoimmune and cholestatic liver disease. PMID:21497742

  15. The mechanisms behind helminth's immunomodulation in autoimmunity.

    PubMed

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

    2015-02-01

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

  16. Total lymphoid irradiation in alloimmunity and autoimmunity

    SciTech Connect

    Strober, S.

    1987-12-01

    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.

  17. Autoimmune Hepatitis with Anti Centromere Antibodies

    PubMed Central

    Lodh, Moushumi; Pradhan, Debkant; Parida, Ashok

    2013-01-01

    We present the case report of a 49-year-old type 2 diabetes mellitus patient presenting with abdominal pain and black stool for 15 days. A proper workup of laboratory investigations helped us diagnose autoimmune hepatitis with anticentromere antibodies. The authors would like to highlight that screening AIH patients for anticentromere antibody is not mandatory but can be considered, especially in the presence of disease-related symptomatology for quicker, more accurate diagnosis and optimum management. PMID:25379307

  18. Natural regulatory T cells in autoimmunity

    PubMed Central

    Lourenço, Elaine V.; La Cava, Antonio

    2010-01-01

    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

  19. Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

    PubMed Central

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

    2006-01-01

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

  20. Refractory Autoimmune Hepatitis: Beyond Standard Therapy.

    PubMed

    Rubin, Jonah N; Te, Helen S

    2016-06-01

    Autoimmune hepatitis (AIH) can be difficult to control, particularly in some African-Americans. When standard therapy of prednisone and azathioprine is ineffective or poorly tolerated, alternative therapies are resorted to. We report two patients with AIH who were refractory to or intolerant of standard therapy. They initially responded to a combination of tacrolimus and MMF, but eventually developed acute flares of the disease that had to be managed with sirolimus, and in one case, rituximab, to achieve remission. PMID:26725067

  1. THE AUTOIMMUNE CONSTELLATION IN LICHEN AMYLOIDOSIS.

    PubMed

    Andrese, Elena; Vâţă, D; Ciobanu, Delia; Stătescu, Laura; Solovăstru, Laura Gheucă

    2015-01-01

    Localized cutaneous amyloidosis is a rare disease among white people, being more common in South-Asia, China and South America. The disease is characterized by deposition of amyloid material in the papillary dermis without visceral involvement. Nevertheless, there is a growing list of immune-mediated disorders that have been linked to cutaneous amyloidosis. We present two cases of concomitant occurrence of lichen amyloidosis and autoimmune thyroiditis/atopic dermatitis in two Caucasian women. PMID:26793847

  2. Association between chronic urticaria and thyroid autoimmunity.

    PubMed

    Cebeci, Filiz; Tanrikut, Ayşenur; Topcu, Elif; Onsun, Nahide; Kurtulmus, Neslihan; Uras, Ahmet R

    2006-01-01

    The association between chronic idiopathic urticaria (CIU) and thyroid autoimmunity has most often been suggested in studies investigating thyroid microsomal antibodies, which are less sensitive and specific than anti-thyroperoxidase antibodies, moreover these studies were not case-control studies in large series. By comparing a large patient series presenting with CIU with a large numbered control group we aimed to learn the extent of autoimmune thyroid disease. We compared the frequency of thyroid autoantibodies in 140 patients with CIU with 181 age-and sex-matched volunteers. Thyroid function tests and thyroid autoantibodies were measured by chemiluminescent immunometric assay in study groups. The frequency of thyroid autoantibodies was significantly higher in patients with CIU than that in healthy controls (29.28 %/5.52%; p < 0.001). Of 41 patients, 10 had thyroid dysfunction and the other cases were euthyroid. The higher frequency of these antibodies in our patients shows that there was a strong association between CIU and thyroid autoimmunity. PMID:16935798

  3. Environmentally induced autoimmune diseases: potential mechanisms.

    PubMed Central

    Rao, T; Richardson, B

    1999-01-01

    Environmental and other xenobiotic agents can cause autoimmunity. Examples include drug-induced lupus, toxic oil syndrome, and contaminated l-tryptophan ingestion. Numerous mechanisms, based on (italic)in vitro(/italic) evidence and animal models, have been proposed to explain how xenobiotics induce or accelerate autoimmunity. The majority of these can be divided into three general categories. The first is those inhibiting the processes involved in establishing tolerance by deletion. Inhibiting deletion can result in the release of newly generated autoreactive cells into the periphery. The second mechanism is the modification of gene expression in the cells participating in the immune response, permitting lymphocytes to respond to signals normally insufficient to initiate a response or allowing the antigen-presenting cells to abnormally stimulate a response. Abnormal gene expression can thus disrupt tolerance maintained by suppression or anergy, permitting activation of autoreactive cells. The third is the modification of self-molecules such that they are recognized by the immune system as foreign. Examples illustrating these concepts are presented, and related mechanisms that have the potential to similarly affect the immune system are noted. Some mechanisms appear to be common to a variety of agents, and different mechanisms appear to produce similar diseases. However, evidence that any of these mechanisms are actually responsible for xenobiotic-induced human autoimmune disease is still largely lacking, and the potential for numerous and as yet unidentified mechanisms also exists. PMID:10502539

  4. Neuronal Surface Antibody-Mediated Autoimmune Encephalitis

    PubMed Central

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

    2016-01-01

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

  5. Automation, consolidation, and integration in autoimmune diagnostics.

    PubMed

    Tozzoli, Renato; D'Aurizio, Federica; Villalta, Danilo; Bizzaro, Nicola

    2015-08-01

    Over the past two decades, we have witnessed an extraordinary change in autoimmune diagnostics, characterized by the progressive evolution of analytical technologies, the availability of new tests, and the explosive growth of molecular biology and proteomics. Aside from these huge improvements, organizational changes have also occurred which brought about a more modern vision of the autoimmune laboratory. The introduction of automation (for harmonization of testing, reduction of human error, reduction of handling steps, increase of productivity, decrease of turnaround time, improvement of safety), consolidation (combining different analytical technologies or strategies on one instrument or on one group of connected instruments) and integration (linking analytical instruments or group of instruments with pre- and post-analytical devices) opened a new era in immunodiagnostics. In this article, we review the most important changes that have occurred in autoimmune diagnostics and present some models related to the introduction of automation in the autoimmunology laboratory, such as automated indirect immunofluorescence and changes in the two-step strategy for detection of autoantibodies; automated monoplex immunoassays and reduction of turnaround time; and automated multiplex immunoassays for autoantibody profiling. PMID:26138781

  6. The Dopaminergic System in Autoimmune Diseases

    PubMed Central

    Pacheco, Rodrigo; Contreras, Francisco; Zouali, Moncef

    2014-01-01

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

  7. Renal involvement in autoimmune connective tissue diseases

    PubMed Central

    2013-01-01

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

  8. Achalasia and thyroid disease: possible autoimmune connection?

    PubMed

    Quidute, Ana Rosa P; Freitas, Eduardo Vasconcelos de; Lima, Tadeu Gonçalves de; Feitosa, Ana Márcia Lima; Santos, Joyce Paiva dos; Correia, José Walter

    2012-12-01

    Many cases have been published showing a co-existence of autoimmune thyroid diseases (AITDs) and other autoimmune diseases. About a quarter of patients with achalasia have a concurrent thyroid disease, most commonly associated with hypothyroidism. Although relatively rare, the association of achalasia and hyperthyroidism requires attention. The physiopathology of Grave's Disease (GD) involves B- and T-mediator lymphocytes, which have an affinity for known thyroid antigens: thyroglobulin, thyroid-peroxidase, and thyrotrophin receptor. Currently, however, the real physiopathogenesis of achalasia continues to be unknown. Some important findings are suggestive of an autoimmune mechanism: significant infiltration of the myoenteric plexus by monocytes, presence of the class II-Human Histocompatibility Complex DQwl antigen and antibodies to myoenteric neurons. The present case reports a patient who, despite testing negative for Chagas' disease, had achalasia, progressed to developing significant wasting and worsening of his quality of life, was later diagnosed with hyperthyroidism. After endoscopic esophageal dilatation and radioiodine ablation of the thyroid gland, there was great improvement in the patient clinical condition. PMID:23329193

  9. Autoimmune thyroiditis associated with neuromyelitis optica (NMO).

    PubMed

    Sudulagunta, Sreenivasa Rao; Sodalagunta, Mahesh Babu; Khorram, Hadi; Sepehrar, Mona; Gonivada, Jayadevappa; Noroozpour, Zahra; Prasad, Nagendra

    2015-01-01

    Neuromyelitis optica (NMO or Devic's syndrome) is a rare relapsing demyelinating disease of the central nervous system (CNS) that mainly affects the spinal cord and optic nerves and shares many clinical and radiological features with multiple sclerosis. The association of NMO with other autoimmune diseases was reported, but very few reports described association with autoimmune thyroid disease. Early differentiation between NMO and multiple sclerosis is very important as the natural course and treatment regimens differ significantly. We report a case of a 50-year-old woman who was admitted initially with vomiting, hiccups and paraesthesias but was not diagnosed with NMO and presented with a severe progression of the disease. The patient was also diagnosed to have autoimmune thyroiditis with lymphocytic infiltration of the thyroid which progressed from hyperthyroidism to hypothyroidism. NMO diagnosis was established with seropositivity for NMO-IgG and MRI showing longitudinally extensive spinal cord lesions (3 or more spinal segments). In spite of treatment, the response was poor due to lack of early diagnosis and aggressive immunosuppressant therapy. PMID:26633965

  10. [Vaccinations in patients with autoimmune diseases].

    PubMed

    Bühler, Silja; Hatz, Christoph

    2016-01-01

    The number of individuals with autoimmune diseases treated with immunosuppressive drugs is increasing steadily. The variety of immunosuppressive drugs and in particular biological therapies is also rising. The autoimmune disease itself as well as the immunosuppressive therapy increases the risk of infection in this population. Particularly the risk of vaccine-preventable infections is elevated. Thus, preventing infections by the means of vaccination is of utmost importance. The Division of Infectious Diseases of the Epidemiology, Biostatistics and Prevention Institute, University of Zurich, performed a literature search on the topic of vaccinations in patients with autoimmune diseases upon request by the Swiss Federal Commission for Vaccination Issues. Overall, data are scarce. The following main points were retrieved from the literature: Inactivated vaccines are safe, but their immunogenicity may be reduced under immunosuppressive therapy. In addition to the generally recommended basic vaccinations, specific vaccinations, such as influenza and pneumococcal vaccination are indicated in these patient groups. Live vaccines are generally contraindicated under immunosuppressive therapy due to safety concerns. However, specific exceptions apply. Furthermore, certain time intervals for the administration of live vaccines after pausing or ceasing an immunosuppressive therapy should be respected. PMID:27268452

  11. Autoimmune Pathogenesis of Chagas Heart Disease

    PubMed Central

    Bonney, Kevin M.; Engman, David M.

    2016-01-01

    Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of individuals infected with the protozoan parasite Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas >100 years ago, much has been learned about Chagas disease pathogenesis; however, the outcome of T. cruzi infection is highly variable and difficult to predict. Many mechanisms have been proposed to promote tissue inflammation, but the determinants and the relative importance of each have yet to be fully elucidated. The notion that some factor other than the parasite significantly contributes to the development of myocarditis was hypothesized by the first physician-scientists who noted the conspicuous absence of parasites in the hearts of those who succumbed to Chagas disease. One of these factors—autoimmunity—has been extensively studied for more than half a century. Although questions regarding the functional role of autoimmunity in the pathogenesis of Chagas disease remain unanswered, the development of autoimmune responses during infection clearly occurs in some individuals, and the implications that this autoimmunity may be pathogenic are significant. In this review, we summarize what is known about the pathogenesis of Chagas heart disease and conclude with a view of the future of Chagas disease diagnosis, pathogenesis, therapy, and prevention, emphasizing recent advances in these areas that aid in the management of Chagas disease. PMID:25857229

  12. Targeting the Fc receptor in autoimmune disease

    PubMed Central

    Li, Xinrui; Kimberly, Robert P

    2014-01-01

    Introduction The Fc receptors and their interaction with immunoglobulin and innate immune opsonins such as CRP are key players in humoral and cellular immune responses. As the effector mechanism for some therapeutic monoclonal antibodies and often a contributor to the pathogenesis and progression of autoimmunity, FcRs are promising targets for treating autoimmune diseases. Areas covered This review discusses the nature of different Fc receptors and the various mechanisms of their involvement in initiating and modulating immunocyte functions and their biological consequences. It describes a range of current strategies in targeting Fc receptors and manipulating their interaction with specific ligands while presenting the pros and cons of these approaches. This review also discusses potential new strategies including regulation of FcR expression and receptor cross-talk. Expert opinion Fc receptors are appealing targets in the treatment of inflammatory autoimmune diseases. However, there are still knowledge limitations and technical challenges, the most important being a better understanding of the individual roles of each of the Fc receptors and enhancement of the specificity in targeting particular cell types and specific Fc receptors. PMID:24521454

  13. Assessment of Virally Vectored Autoimmunity as a Biocontrol Strategy for Cane Toads

    PubMed Central

    Robinson, Anthony J.; Venables, Daryl; Voysey, Rhonda D.; Boyle, Donna G.; Shanmuganathan, Thayalini; Hardy, Christopher M.; Siddon, Nicole A.; Hyatt, Alex D.

    2011-01-01

    Background The cane toad, Bufo (Chaunus) marinus, is one of the most notorious vertebrate pests introduced into Australia over the last 200 years and, so far, efforts to identify a naturally occurring B. marinus-specific pathogen for use as a biological control agent have been unsuccessful. We explored an alternative approach that entailed genetically modifying a pathogen with broad host specificity so that it no longer caused disease, but carried a gene to disrupt the cane toad life cycle in a species specific manner. Methodology/Principal Findings The adult beta globin gene was selected as the model gene for proof of concept of autoimmunity as a biocontrol method for cane toads. A previous report showed injection of bullfrog tadpoles with adult beta globin resulted in an alteration in the form of beta globin expressed in metamorphs as well as reduced survival. In B. marinus we established for the first time that the switch from tadpole to adult globin exists. The effect of injecting B. marinus tadpoles with purified recombinant adult globin protein was then assessed using behavioural (swim speed in tadpoles and jump length in metamorphs), developmental (time to metamorphosis, weight and length at various developmental stages, protein profile of adult globin) and genetic (adult globin mRNA levels) measures. However, we were unable to detect any differences between treated and control animals. Further, globin delivery using Bohle iridovirus, an Australian ranavirus isolate belonging to the Iridovirus family, did not reduce the survival of metamorphs or alter the form of beta globin expressed in metamorphs. Conclusions/Significance While we were able to show for the first time that the switch from tadpole to adult globin does occur in B. marinus, we were not able to induce autoimmunity and disrupt metamorphosis. The short development time of B. marinus tadpoles may preclude this approach. PMID:21283623

  14. Type I enteropathy-associated T-cell lymphoma in the colon of a 29-year-old patient and a brief literature review

    PubMed Central

    Zhang, Jiu-Cong; Wang, Yong; Wang, Xiu-Feng; Zhang, Fang-Xin

    2016-01-01

    Enteropathy-associated T-cell lymphoma (EATL) is a rare gastrointestinal non-Hodgkin’s lymphoma, originating from intraepithelial T-lymphocyte, which is specifically associated with celiac disease. EATL most commonly presents in the sixth and seventh decades of life. We report a unique case of type I EATL in the colon with liver metastasis, which was presented with nonspecific radiological findings and at a very young age (29 years old) compared with previously published data. We suggest that EATL should be regarded as part of differential diagnosis in any patient presenting with abdominal pain, diarrhea, weight loss, and malabsorption because delay in treatment can result in an irreversible clinical outcome. PMID:26955284

  15. Open questions in autoimmunity: discussions from the 2013 Controversies in Rheumatology and Autoimmunity Meeting.

    PubMed

    Selmi, Carlo; Shoenfeld, Yehuda

    2014-01-01

    The recent CORA (Controversies in Rheumatology and Autoimmunity) meeting held in 2013 represented a unique opportunity for rheumatologists to address several topics. Among these, four topics include: (i) the role of epigenetic changes in the pathogenesis of rheumatoid arthritis (RA), as shown by studies in monozygotic twins; (ii) the cardiovascular and atherosclerotic risk in patients with RA treated with biologics; (iii) the use of new biomarkers for the diagnosis and follow-up of RA and other autoimmune diseases, as represented by the new automatic machines for anti-nuclear antibodies detection, or ultrasound imaging to follow RA progression; and (iv) the latest guidelines on how to use and manage biologic therapies in RA and other autoimmune diseases, such as lupus. In summary, we will herein present these topics of discussion and underline the conclusions obtained by rheumatologists during the 2013 CORA Meeting. PMID:24642104

  16. [Enteropathy due to olmesartan].

    PubMed

    Ould Sidi Mohamed, M; Colardelle, P

    2016-04-01

    The olmesartan is a selective antagonist of angiotensin II indicated for the treatment of essential hypertension. We report the case of a gastrointestinal involvement with duodenal villous atrophy and lymphocytic infiltrate duodenal epithelial and colonic secondary to the olmesartan taking with test of positive reintroduction. The patient had chronic diarrhea with weight loss of 10kg occurred 1month after the passage of 20 to 40mg/day olmesartan took 3years. A rectosigmoidoscopy highlighted some puncture slightly erythematous areas. The responsibility of olmesartan was suspected and the drug was stopped. The evolution was rapidly favorable with disappearance of diarrhea 48hours later. Two days after the patient took the drug on its own initiative. Sigmoid biopsies showed an inflammatory infiltrate rich in lymphocytes. Gastroscopy showed erosive esophagitis and duodenal biopsies showed chronic duodenitis with epithelial lymphocytosis and subtotal villous atrophy. The reintroduction has led to the immediate resumption of diarrhea. olmetec was finalized. Diarrhea has not returned since. A colonoscopy performed 6weeks after discharge was normal. Knowledge of the bowel olmesartan is recent and based almost solely on the description of 22 cases observed at the Mayo Clinic with patients, as in our case, have similar symptoms and lesions. We stress about a publication an isolated case the possibility of less severe cases with histological abnormalities without clinical translation. PMID:26067144

  17. Celiac Disease Autoimmunity in Patients with Autoimmune Diabetes and Thyroid Disease among Chinese Population.

    PubMed

    Zhao, Zhiyuan; Zou, Jing; Zhao, Lingling; Cheng, Yan; Cai, Hanqing; Li, Mo; Liu, Edwin; Yu, Liping; Liu, Yu

    2016-01-01

    The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) amongst patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001) or NAITD (3.1%; P < 0.0001) or healthy controls (1%; p<0.0001). The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients. PMID:27427767

  18. Celiac Disease Autoimmunity in Patients with Autoimmune Diabetes and Thyroid Disease among Chinese Population

    PubMed Central

    Zhao, Zhiyuan; Zou, Jing; Zhao, Lingling; Cheng, Yan; Cai, Hanqing; Li, Mo; Liu, Edwin; Yu, Liping; Liu, Yu

    2016-01-01

    The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) amongst patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001) or NAITD (3.1%; P < 0.0001) or healthy controls (1%; p<0.0001). The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients. PMID:27427767

  19. The MicroRNA-21 in Autoimmune Diseases

    PubMed Central

    Wang, Shaowen; Wan, Xiaochun; Ruan, Qingguo

    2016-01-01

    MicroRNA-21 (miR-21) is an oncomiR and significantly upregulated in a wide range of cancers. It is strongly involved in apoptosis and oncogenesis, since most of its reported targets are tumor suppressors. Recently, miR-21 was found to be correlated with the pathogenesis of autoimmune diseases and may play an essential role in regulating autoimmune responses. In particular, miR-21 promotes Th17 cell differentiation, which mediates the development of multiple autoimmune diseases. In this article, we review the current research on the mechanisms that regulate miR-21 expression, the potential of miR-21 as a diagnostic biomarker for autoimmune disease and the mechanisms by which miR-21 promotes the development of autoimmune disease. We also discussed the therapeutic potential of targeting miR-21 in treating patients with autoimmune disease. PMID:27271606

  20. Immunodeficiency and autoimmunity: lessons from systemic lupus erythematosus

    PubMed Central

    Grammatikos, Alexandros P.; Tsokos, George C.

    2011-01-01

    Recent evidence suggests that systemic autoimmunity and immunodeficiency are not separate entities, but rather interconnected processes. Immunodeficiency results from distinct defects of the immune response and primarily presents as infections, but also frequently with autoimmune features. Systemic autoimmunity is the combined effect of multiple genetic variations, infectious and immunoregulatory factors that result in dominant autoimmune manifestations in addition to frequent and opportunistic infections. The overlap in disease manifestations and symptoms suggests that immunodeficiency should be considered in the presence of autoimmunity, and vice versa. In this review, we present the shared or similar aspects of immunodeficiency and autoimmunity using systemic lupus erythematosus as a paradigm and discuss the implications for clinical care. PMID:22177735

  1. Smoke and autoimmunity: The fire behind the disease.

    PubMed

    Perricone, Carlo; Versini, Mathilde; Ben-Ami, Dana; Gertel, Smadar; Watad, Abdulla; Segel, Michael J; Ceccarelli, Fulvia; Conti, Fabrizio; Cantarini, Luca; Bogdanos, Dimitrios P; Antonelli, Alessandro; Amital, Howard; Valesini, Guido; Shoenfeld, Yehuda

    2016-04-01

    The association between smoke habit and autoimmunity has been hypothesized a long time ago. Smoke has been found to play a pathogenic role in certain autoimmune disease as it may trigger the development of autoantibodies and act on pathogenic mechanism possibly related with an imbalance of the immune system. Indeed, both epidemiological studies and animal models have showed the potential deleterious effect caused by smoke. For instance, smoke, by provoking oxidative stress, may contribute to lupus disease by dysregulating DNA demethylation, upregulating immune genes, thereby leading to autoreactivity. Moreover, it can alter the lung microenvironment, facilitating infections, which, in turn, may trigger the development of an autoimmune condition. This, in turn, may result in a dysregulation of immune system leading to autoimmune phenomena. Not only cigarette smoke but also air pollution has been reported as being responsible for the development of autoimmunity. Large epidemiological studies are needed to further explore the accountability of smoking effect in the pathogenesis of autoimmune diseases. PMID:26772647

  2. Autoimmune myasthenia gravis, immunotherapy and thymectomy in children.

    PubMed

    Ware, Tyson L; Ryan, Monique M; Kornberg, Andrew J

    2012-02-01

    Autoimmune myasthenia gravis is a rare condition in children. Identifying antibodies directed against the acetylcholine receptor is helpful in making the diagnosis. However, seronegative cases do exist and need to be distinguished from congenital forms of myasthenia. There is little published experience to inform the judicious management of autoimmune myasthenia gravis in children. In this article, we report our experience in the management of 12 cases of autoimmune myasthenia gravis in children in the modern era of medical immunotherapy and thymectomy. PMID:21911294

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

    PubMed Central

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

    2015-01-01

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

  4. Ovarian autoimmune disease: clinical concepts and animal models

    PubMed Central

    Warren, Bryce D; Kinsey, William K; McGinnis, Lynda K; Christenson, Lane K; Jasti, Susmita; Stevens, Anne M; Petroff, Brian K; Petroff, Margaret G

    2014-01-01

    The ovary is not an immunologically privileged organ, but a breakdown in tolerogenic mechanisms for ovary-specific antigens has disastrous consequences on fertility in women, and this is replicated in murine models of autoimmune disease. Isolated ovarian autoimmune disease is rare in women, likely due to the severity of the disease and the inability to transmit genetic information conferring the ovarian disease across generations. Nonetheless, autoimmune oophoritis is often observed in association with other autoimmune diseases, particularly autoimmune adrenal disease, and takes a toll on both society and individual health. Studies in mice have revealed at least two mechanisms that protect the ovary from autoimmune attack. These mechanisms include control of autoreactive T cells by thymus-derived regulatory T cells, as well as a role for the autoimmune regulator (AIRE), a transcriptional regulator that induces expression of tissue-restricted antigens in medullary thymic epithelial cells during development of T cells. Although the latter mechanism is incompletely defined, it is well established that failure of either results in autoimmune-mediated targeting and depletion of ovarian follicles. In this review, we will address the clinical features and consequences of autoimmune-mediated ovarian infertility in women, as well as the possible mechanisms of disease as revealed by animal models. PMID:25327908

  5. Epigenetics of autoantigens: new opportunities for therapy of autoimmune diseases.

    PubMed

    Radic, Marko; Muller, Sylviane

    2013-01-01

    The field of epigenetics requires that traditional divisions between scientific disciplines give way to cross-fertilization of concepts and ideas from different areas of investigation. Such is the case with research in autoimmunity. Recent discoveries of stimuli that induce autoimmunity reveal that epigenetic marks of autoantigens are recognized by autoreactive B and T cell receptors. Thus, insights into the initiation of autoimmunity, its prevention and therapy will arise from understanding the biochemistry, cell biology and microbiology of autoantigen epigenetics. Here, we highlight potential benefits from the inhibition of a histone modifying enzyme and the administration of a phosphorylated, spliceosome-derived peptide, in the treatment of autoimmunity. PMID:25512708

  6. The target tissue in autoimmunity--an influential niche.

    PubMed

    Hill, Natasha J; Hultcrantz, Monica; Sarvetnick, Nora; Flodström-Tullberg, Malin

    2007-03-01

    Central and peripheral tolerance mechanisms were for a long time the only regulatory circuits known in autoimmunity. It is now becoming clear that the target tissue itself may have the capacity to control its own destiny. Here we review mechanisms by which the target tissue regulates local inflammation, and the way this could influence progression to overt autoimmunity. Moreover, we discuss recent data showing that physiological properties of the target tissue can determine the organ specificity of autoimmune disease. These recent discoveries and ideas concerning the regulatory potential of the target tissue may, in the future, add a new dimension to our concept of regulatory circuits in autoimmunity. PMID:17301949

  7. Autoimmune vitiligo in rheumatic disease in the mestizo Mexican population

    PubMed Central

    Avalos-Díaz, Esperanza; Pérez-Pérez, Elena; Rodríguez-Rodríguez, Mayra; Pacheco-Tovar, María-Guadalupe; Herrera-Esparza, Rafael

    2016-01-01

    Vitiligo is a chronic disease characterized by the dysfunction or destruction of melanocytes with secondary depigmentation. The aim of the present study was to determine the prevalence of vitiligo associated with autoimmune rheumatic diseases. The clinical records from a 10-year database of patients with rheumatic diseases and associated vitiligo was analysed, with one group of patients having autoimmune rheumatic disease and another non-autoimmune rheumatic disease. Available serum samples were used to assess the anti-melanocyte antibodies. A total of 5,251 individual clinical files were archived in the last 10 years, and these patients underwent multiple rheumatology consultations, with 0.3% of the group presenting with vitiligo. The prevalence of vitiligo in the autoimmune rheumatic disease group was 0.672%, which was mainly associated with lupus and arthritis. However, patients with more than one autoimmune disease had an increased relative risk to develop vitiligo, and anti-melanocyte antibodies were positive in 92% of these patients. By contrast, the prevalence was 0.082% in the group that lacked autoimmune rheumatic disease and had negative autoantibodies. In conclusion, the association between vitiligo and autoimmune rheumatic diseases was relatively low. However, the relative risk increased when there were other autoimmune comorbidities, such as thyroiditis or celiac disease. Therefore, the presence of multiple autoimmune syndromes should be suspected. PMID:27446537

  8. Human immunodeficiency virus infection and autoimmune hepatitis during highly active anti-retroviral treatment: a case report and review of the literature

    PubMed Central

    2011-01-01

    Introduction The emergence of hepatic injury in patients with human immunodeficiency virus infection during highly active therapy presents a diagnostic dilemma. It may represent treatment side effects or autoimmune disorders, such as autoimmune hepatitis, emerging during immune restoration. Case presentation We present the case of a 42-year-old African-American woman with human immunodeficiency virus infection who presented to our emergency department with severe abdominal pain and was found to have autoimmune hepatitis. A review of the literature revealed 12 reported cases of autoimmune hepatitis in adults with human immunodeficiency virus infection, only three of whom were diagnosed after highly active anti-retroviral treatment was initiated. All four cases (including our patient) were women, and one had a history of other autoimmune disorders. In our patient (the one patient case we are reporting), a liver biopsy revealed interface hepatitis, necrosis with lymphocytes and plasma cell infiltrates and variable degrees of fibrosis. All four cases required treatment with corticosteroids and/or other immune modulating agents and responded well. Conclusion Our review suggests that autoimmune hepatitis is a rare disorder which usually develops in women about six to eight months after commencing highly active anti-retroviral treatment during the recovery of CD4 lymphocytes. It represents either re-emergence of a pre-existing condition that was unrecognized or a de novo manifestation during immune reconstitution. PMID:21702972

  9. Melanocyte antigen triggers autoimmunity in human psoriasis.

    PubMed

    Arakawa, Akiko; Siewert, Katherina; Stöhr, Julia; Besgen, Petra; Kim, Song-Min; Rühl, Geraldine; Nickel, Jens; Vollmer, Sigrid; Thomas, Peter; Krebs, Stefan; Pinkert, Stefan; Spannagl, Michael; Held, Kathrin; Kammerbauer, Claudia; Besch, Robert; Dornmair, Klaus; Prinz, Jörg C

    2015-12-14

    Psoriasis vulgaris is a common T cell-mediated inflammatory skin disease with a suspected autoimmune pathogenesis. The human leukocyte antigen (HLA) class I allele, HLA-C*06:02, is the main psoriasis risk gene. Epidermal CD8(+) T cells are essential for psoriasis development. Functional implications of HLA-C*06:02 and mechanisms of lesional T cell activation in psoriasis, however, remained elusive. Here we identify melanocytes as skin-specific target cells of an HLA-C*06:02-restricted psoriatic T cell response. We found that a Vα3S1/Vβ13S1 T cell receptor (TCR), which we had reconstituted from an epidermal CD8(+) T cell clone of an HLA-C*06:02-positive psoriasis patient specifically recognizes HLA-C*06:02-positive melanocytes. Through peptide library screening, we identified ADAMTS-like protein 5 (ADAMTSL5) as an HLA-C*06:02-presented melanocytic autoantigen of the Vα3S1/Vβ13S1 TCR. Consistent with the Vα3S1/Vβ13S1-TCR reactivity, we observed numerous CD8(+) T cells in psoriasis lesions attacking melanocytes, the only epidermal cells expressing ADAMTSL5. Furthermore, ADAMTSL5 stimulation induced the psoriasis signature cytokine, IL-17A, in CD8(+) T cells from psoriasis patients only, supporting a role as psoriatic autoantigen. This unbiased analysis of a TCR obtained directly from tissue-infiltrating CD8(+) T cells reveals that in psoriasis HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation. We propose that HLA-C*06:02 may predispose to psoriasis via this newly identified autoimmune pathway. PMID:26621454

  10. Large leg ulcers due to autoimmune diseases

    PubMed Central

    Rozin, Alexander P.; Egozi, Dana; Ramon, Yehuda; Toledano, Kohava; Braun-Moscovici, Yolanda; Markovits, Doron; Schapira, Daniel; Bergman, Reuven; Melamed, Yehuda; Ullman, Yehuda; Balbir-Gurman, Alexandra

    2011-01-01

    Summary Background Large leg ulcers (LLU) may complicate autoimmune diseases. They pose a therapeutic challenge and are often resistant to treatment. To report three cases of autoimmune diseases complicated with LLU. Case Report Case 1. A 55-year old woman presented with long-standing painful LLU due to mixed connective tissue disease (MCTD). Biopsy from the ulcer edge showed small vessel vasculitis. IV methylprednisolone (MethP) 1 G/day, prednisolone (PR) 1mg/kg, monthly IV cyclophosphamide (CYC), cyclosporine (CyA) 100mg/day, IVIG 125G, ciprofloxacin+IV Iloprost+enoxaparin+aspirin (AAVAA), hyperbaric oxygen therapy (HO), maggot debridement and autologous skin transplantation were performed and the LLU healed. Case 2. A 45-year old women with MCTD developed multiple LLU’s with non-specific inflammation by biopsy. MethP, PR, hydroxychloroquine (HCQ), azathioprine (AZA), CYC, IVIG, AAVAA failed. Treatment for underlying the LLU tibial osteomyelitis and addition of CyA was followed by the LLU healing. Case 3. A 20-year-old man with history of polyarteritis nodosa (PAN) developed painful LLU’s due to small vessel vasculitis (biopsy). MethP, PR 1 mg/kg, CYC, CyA 100 mg/d, AAVAA failed. MRSA sepsis and relapse of systemic PAN developed. IV vancomycin, followed by ciprofloxacin, monthly IVIG (150 g/for 5 days) and infliximab (5 mg/kg) were instituted and the LLU’s healed. Conclusions LLU are extremely resistant to therapy. Combined use of multiple medications and services are needed for healing of LLU due to autoimmune diseases. PMID:21169912

  11. Melanocyte antigen triggers autoimmunity in human psoriasis

    PubMed Central

    Arakawa, Akiko; Siewert, Katherina; Stöhr, Julia; Besgen, Petra; Kim, Song-Min; Rühl, Geraldine; Nickel, Jens; Vollmer, Sigrid; Thomas, Peter; Krebs, Stefan; Pinkert, Stefan; Spannagl, Michael; Held, Kathrin; Kammerbauer, Claudia; Besch, Robert; Dornmair, Klaus

    2015-01-01

    Psoriasis vulgaris is a common T cell–mediated inflammatory skin disease with a suspected autoimmune pathogenesis. The human leukocyte antigen (HLA) class I allele, HLA-C*06:02, is the main psoriasis risk gene. Epidermal CD8+ T cells are essential for psoriasis development. Functional implications of HLA-C*06:02 and mechanisms of lesional T cell activation in psoriasis, however, remained elusive. Here we identify melanocytes as skin-specific target cells of an HLA-C*06:02–restricted psoriatic T cell response. We found that a Vα3S1/Vβ13S1 T cell receptor (TCR), which we had reconstituted from an epidermal CD8+ T cell clone of an HLA-C*06:02–positive psoriasis patient specifically recognizes HLA-C*06:02–positive melanocytes. Through peptide library screening, we identified ADAMTS-like protein 5 (ADAMTSL5) as an HLA-C*06:02–presented melanocytic autoantigen of the Vα3S1/Vβ13S1 TCR. Consistent with the Vα3S1/Vβ13S1-TCR reactivity, we observed numerous CD8+ T cells in psoriasis lesions attacking melanocytes, the only epidermal cells expressing ADAMTSL5. Furthermore, ADAMTSL5 stimulation induced the psoriasis signature cytokine, IL-17A, in CD8+ T cells from psoriasis patients only, supporting a role as psoriatic autoantigen. This unbiased analysis of a TCR obtained directly from tissue-infiltrating CD8+ T cells reveals that in psoriasis HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation. We propose that HLA-C*06:02 may predispose to psoriasis via this newly identified autoimmune pathway. PMID:26621454

  12. [Atopy and autoimmunity -- a case report].

    PubMed

    Alfaro, M; Tapadinhas, F; Neves, Am; Costa Trindade, J

    2007-01-01

    Atopy, immunodeficiency and autoimmunity are manifestations of immune system dysfunction. Classically atopy and autoimmunity are referred as distinct immunological reactions. Recent studies suggest the existence of common pathogenic mechanisms. We report the case of a teenager with familial history of asthma and miasthenia gravis in her mother (HLA- B8+) and personal history of recurrent upper respiratory infections from two to four years old, and pneumonia since five years old (3 or 4 episodes/ year, in three consecutive years), with associated dyspnoea and hypoxemia, requiring frequently hospital admission. Investigation was initially negative for atopy markers, and excluded other hypothesis as tuberculosis, cystic fibrosis, -1 antitrypsin deficiency, congenital heart disease, bronchopulmonary malformations or foreign body aspiration. Latter, further exams finally confirmed atopy with a raised IgE, positive RAST and cutaneous sensitivity tests (for house dust mites and pollen) and revealed circulating immune complexes and IgG 2, 3 e 4 deficit. Most frequent autoantibodies and precipitins study were negative, and histocompatibility antigens study revealed HLA- B8 (as her mother). Ventilation-perfusion scintigraphy and respiratory function tests were normal. Antihistamines, topical corticoids and bronchodilators were done with an excellent clinical response. At 16 years- old she is admitted again with the diagnosis of erythema nodosum and the clinical suspicion of Sweet's syndrome, having a good evolution. The relation between atopy and autoimmunity is enfatized by the authors. This simultaneous occurrence does not correspond merely to a statistical association, but may represent a global immune system impairment, with the involvement of different types of hypersensibility. PMID:17962891

  13. Dendritic cells in autoimmune thyroid disease.

    PubMed

    Kabel, P J; Voorbij, H A; van der Gaag, R D; Wiersinga, W M; de Haan, M; Drexhage, H A

    1987-01-01

    Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20-30% were seen in contact with now-present intrathyroidal T-helper lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3475920

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

    PubMed

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

    2016-01-01

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

  15. Familial Aggregation and Segregation Analysis in Families Presenting Autoimmunity, Polyautoimmunity, and Multiple Autoimmune Syndrome

    PubMed Central

    Castiblanco, John; Sarmiento-Monroy, Juan Camilo; Mantilla, Ruben Dario; Rojas-Villarraga, Adriana; Anaya, Juan-Manuel

    2015-01-01

    Studies documenting increased risk of developing autoimmune diseases (ADs) have shown that these conditions share several immunogenetic mechanisms (i.e., the autoimmune tautology). This report explored familial aggregation and segregation of AD, polyautoimmunity, and multiple autoimmune syndrome (MAS) in 210 families. Familial aggregation was examined for first-degree relatives. Segregation analysis was implemented as in S.A.G.E. release 6.3. Data showed differences between late- and early-onset families regarding their age, age of onset, and sex. Familial aggregation of AD in late- and early-onset families was observed. For polyautoimmunity as a trait, only aggregation was observed between sibling pairs in late-onset families. No aggregation was observed for MAS. Segregation analyses for AD suggested major gene(s) with no clear discernible classical known Mendelian transmission in late-onset families, while for polyautoimmunity and MAS no model was implied. Data suggest that polyautoimmunity and MAS are not independent traits and that gender, age, and age of onset are interrelated factors influencing autoimmunity. PMID:26697508

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

    PubMed Central

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

    2016-01-01

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

  17. HLA, NFKB1 and NFKBIA gene polymorphism profile in autoimmune diabetes mellitus patients.

    PubMed

    Katarina, K; Daniela, P; Peter, N; Marianna, R; Pavlina, C; Stepanka, P; Jan, L; Ludmila, T; Michal, A; Marie, C

    2007-02-01

    Type 1 diabetes mellitus (T1DM) is one of the long-time studied autoimmune disorders. The triggering of the autoimmune process has been ascribed to various genes active in the regulation of the cytokine gene transcription including the Rel/NF-kappaB gene family. In our study the gene polymorphism of HLA class II, NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and NFKBIA (inhibitor of nuclear factor kappa B) was tested. Patients were divided into the subgroups in relation to the disease type: T1DM in children, T1DM in adults, and Latent Autoimmune Diabetes in Adults (LADA). HLA-DRB1 (*)04 and HLA-DQB1 (*)0302 have been detected as risk factors for T1DM in adults and particularly in children (P<0.0001, OR=22.9 and 46.5 respectively). HLA-DRB1 (*)03 has been found as a single risk factor for LADA (P<0.0001, OR=4.9). We detected 15 alleles for the NFKB1 gene polymorphism (CA-repeats) in the Czech population. The alleles were ranging in size from 114-142 bp corresponding to 10-25 CA repeats. Frequency of the A7 allele of NFKB1 gene has been significantly increased in T1DM adults (P<0.01). There was no difference in A and a G allele frequency of NFKBIA gene between the control group and patients, but the association of the AA genotype of NFKBIA gene has been found for LADA (P<0.05). Summarizing our results we concluded that there is a high probability of association of gene polymorphism from Rel/NF-kappaB family with an autoimmune diabetes course. Due to the results obtained in the epidemiological study we have been looking also for the function significance of the genetic predisposition. No significant changes have been observed by real time PCR testing of HLA-DRB1 (*)04 gene and NFKB1 gene expression between T1DM diabetic group with different HLA, NFKB1, NFKBIA genetic background. PMID:17318773

  18. Cold agglutinin-mediated autoimmune hemolytic anemia.

    PubMed

    Berentsen, Sigbjørn; Randen, Ulla; Tjønnfjord, Geir E

    2015-06-01

    Cold antibody types account for about 25% of autoimmune hemolytic anemias. Primary chronic cold agglutinin disease (CAD) is characterized by a clonal lymphoproliferative disorder. Secondary cold agglutinin syndrome (CAS) complicates specific infections and malignancies. Hemolysis in CAD and CAS is mediated by the classical complement pathway and is predominantly extravascular. Not all patients require treatment. Successful CAD therapy targets the pathogenic B-cell clone. Complement modulation seems promising in both CAD and CAS. Further development and documentation are necessary before clinical use. We review options for possible complement-directed therapy. PMID:26043385

  19. Role of extracellular vesicles in autoimmune diseases.

    PubMed

    Turpin, Delphine; Truchetet, Marie-Elise; Faustin, Benjamin; Augusto, Jean-François; Contin-Bordes, Cécile; Brisson, Alain; Blanco, Patrick; Duffau, Pierre

    2016-02-01

    Extracellular vesicles (EVs) consist of exosomes released upon fusion of multivesicular bodies with the cell plasma membrane and microparticles shed directly from the cell membrane of many cell types. EVs can mediate cell-cell communication and are involved in many processes including inflammation, immune signaling, angiogenesis, stress response, senescence, proliferation, and cell differentiation. Accumulating evidence reveals that EVs act in the establishment, maintenance and modulation of autoimmune processes among several others involved in cancer and cardiovascular complications. EVs could also present biomedical applications, as disease biomarkers and therapeutic targets or agents for drug delivery. PMID:26554931

  20. Autoimmune demyelination in the central nervous system.

    PubMed

    Tabira, T

    1988-01-01

    Autoimmune demyelination was studied in EAE induced by active challenge or by transfer of effector T-cell lines or clones specific for myelin basic protein or proteolipid apoprotein. The following points became clear: (1) Proteolipid apoprotein is responsible for widespread demyelination; (2) demyelination is more significant in EAE with a more chronic disease process; (3) a single T-cell clone can mediate significant demyelination without the aid of recipient-derived T-cell populations; (4) the difference in vulnerability between axons and myelin may account for the T-cell-mediated demyelination; and (5) effector T-cell clones can be activated by allogeneic antigens. PMID:2462801

  1. The Clinical Pictures of Autoimmune Hemolytic Anemia.

    PubMed

    Packman, Charles H

    2015-09-01

    Autoimmune hemolytic anemia is characterized by shortened red blood cell survival and a positive Coombs test. The responsible autoantibodies may be either warm reactive or cold reactive. The rate of hemolysis and the severity of the anemia may vary from mild to severe and life-threatening. Diagnosis is made in the laboratory by the findings of anemia, reticulocytosis, a positive Coombs test, and specific serologic tests. The prognosis is generally good but renal failure and death sometimes occur, especially in cases mediated by drugs. PMID:26696800

  2. The Clinical Pictures of Autoimmune Hemolytic Anemia

    PubMed Central

    Packman, Charles H.

    2015-01-01

    Summary Autoimmune hemolytic anemia is characterized by shortened red blood cell survival and a positive Coombs test. The responsible autoantibodies may be either warm reactive or cold reactive. The rate of hemolysis and the severity of the anemia may vary from mild to severe and life-threatening. Diagnosis is made in the laboratory by the findings of anemia, reticulocytosis, a positive Coombs test, and specific serologic tests. The prognosis is generally good but renal failure and death sometimes occur, especially in cases mediated by drugs. PMID:26696800

  3. AUTOIMMUNE HYPOTHYROIDISM IN PATIENT WITH NEUROFIBROMATOSIS-1.

    PubMed

    Faraz, Ahmed; Nafees, Taha; Ahmed, Syed Arsalan; Rizvi, Shahraiz Shah

    2015-01-01

    A 53 year old woman, diagnosed with Neurofibromatosis I with multiple neurfibromas over trunk, upper limb & lower limb, she had café au lait spots on her abdomen skin. She was admitted to the tertiary care setup with the complains of cold intolerance, numbness in the limbs, high blood pressure & constipation, patient also had complain of weight gain, lab revealed high TSH, low Free thyroid hormones & positive anti thyroglobulin antibodies. Case was diagnosed with autoimmune hypothyroidism. This is the first case reported with such association of these two diseases. PMID:27004358

  4. Treating prolactinoma can prevent autoimmune diseases.

    PubMed

    Watad, Abdulla; Versini, Mathilde; Jeandel, Pierre-Yves; Amital, Howard; Shoenfeld, Yehuda

    2015-04-01

    Prolactin (PRL) is a pleiotropic hormone; in addition to a wide variety of endocrine effects, PRL also exhibits immunostimulating effects. Therefore, there is increasing evidence linking PRL with a large number of systemic and organ specific autoimmune diseases. Herein, we report the case of an adolescent girl diagnosed with multiple sclerosis (MS) occurring in the context of untreated prolactinoma evolving since childhood. This raises the exciting question of the involvement of PRL in the pathogenesis of MS. It is likely that early treatment of hyperprolactinemia in this case would have significantly reduced the risk of developing MS or even prevented its occurrence. PMID:25468803

  5. Insulin Autoimmune Syndrome Accompanied by Multiple Myeloma.

    PubMed

    Ito, Harumi; Miyake, Takafumi; Nakashima, Kazuo; Ito, Yuji; Tanahashi, Chisato; Uchigata, Yasuko

    2016-01-01

    In 1981, a 48-year old man was diagnosed with insulin autoimmune syndrome. In 2005, he experienced a substantial increase in his monoclonal insulin antibody levels; in 2006 and 2007, serum monoclonal gammopathy and an 11% marrow plasmacyte ratio were confirmed. In 2012, asymptomatic multiple myeloma was diagnosed based on an increased γ-globulin fraction and serum M-protein (IgG) levels. The insulin antibody binding rate was 75.4% in 2005 and 78.8% in 2012. In 2012, he was hospitalized for ileus and died. Autopsy identified multiple myeloma and no endocrinological tumors in the pancreas. PMID:27522998

  6. Hypothalamic-Pituitary Autoimmunity and Traumatic Brain Injury

    PubMed Central

    Guaraldi, Federica; Grottoli, Silvia; Arvat, Emanuela; Ghigo, Ezio

    2015-01-01

    Background: Traumatic brain injury (TBI) is a leading cause of secondary hypopituitarism in children and adults, and is responsible for impaired quality of life, disabilities and compromised development. Alterations of pituitary function can occur at any time after the traumatic event, presenting in various ways and evolving during time, so they require appropriate screening for early detection and treatment. Although the exact pathophysiology is unknown, several mechanisms have been hypothesized, including hypothalamic-pituitary autoimmunity (HP-A). The aim of this study was to systematically review literature on the association between HP-A and TBI-induced hypopituitarism. Major pitfalls related to the HP-A investigation were also discussed. Methods: The PubMed database was searched with a string developed for this purpose, without temporal or language limits, for original articles assessing the association of HP-A and TBI-induced hypopituitarism. Results: Three articles from the same group met the inclusion criteria. Anti-pituitary and anti-hypothalamic antibodies were detected using indirect immunofluorescence in a significant number of patients with acute and chronic TBI. Elevated antibody titer was associated with an increased risk of persistent hypopituitarism, especially somatotroph and gonadotroph deficiency, while no correlations were found with clinical parameters. Conclusion: HPA seems to contribute to TBI-induced pituitary damage, although major methodological issues need to be overcome and larger studies are warranted to confirm these preliminary data. PMID:26239463

  7. Regulatory T Cells Control Th2-Dominant Murine Autoimmune Gastritis.

    PubMed

    Harakal, Jessica; Rival, Claudia; Qiao, Hui; Tung, Kenneth S

    2016-07-01

    Pernicious anemia and gastric carcinoma are serious sequelae of autoimmune gastritis (AIG). Our study indicates that in adult C57BL/6-DEREG mice expressing a transgenic diphtheria toxin receptor under the Foxp3 promoter, transient regulatory T cell (Treg) depletion results in long-lasting AIG associated with both H(+)K(+)ATPase and intrinsic factor autoantibody responses. Although functional Tregs emerge over time during AIG occurrence, the effector T cells rapidly become less susceptible to Treg-mediated suppression. Whereas previous studies have implicated dysregulated Th1 cell responses in AIG pathogenesis, eosinophils have been detected in gastric biopsy specimens from patients with AIG. Indeed, AIG in DEREG mice is associated with strong Th2 cell responses, including dominant IgG1 autoantibodies, elevated serum IgE, increased Th2 cytokine production, and eosinophil infiltration in the stomach-draining lymph nodes. In addition, the stomachs exhibit severe mucosal and muscular hypertrophy, parietal cell loss, mucinous epithelial cell metaplasia, and massive eosinophilic inflammation. Notably, the Th2 responses and gastritis severity are significantly ameliorated in IL-4- or eosinophil-deficient mice. Furthermore, expansion of both Th2-promoting IFN regulatory factor 4(+) programmed death ligand 2(+) dendritic cells and ILT3(+) rebounded Tregs was detected after transient Treg depletion. Collectively, these data suggest that Tregs maintain physiological tolerance to clinically relevant gastric autoantigens, and Th2 responses can be a pathogenic mechanism in AIG. PMID:27259856

  8. PRKDC mutations associated with immunodeficiency, granuloma, and autoimmune regulator–dependent autoimmunity

    PubMed Central

    Mathieu, Anne-Laure; Verronese, Estelle; Rice, Gillian I.; Fouyssac, Fanny; Bertrand, Yves; Picard, Capucine; Chansel, Marie; Walter, Jolan E.; Notarangelo, Luigi D.; Butte, Manish J.; Nadeau, Kari Christine; Csomos, Krisztian; Chen, David J.; Chen, Karin; Delgado, Ana; Rigal, Chantal; Bardin, Christine; Schuetz, Catharina; Moshous, Despina; Reumaux, Héloïse; Plenat, François; Phan, Alice; Zabot, Marie-Thérèse; Balme, Brigitte; Viel, Sébastien; Bienvenu, Jacques; Cochat, Pierre; van der Burg, Mirjam; Caux, Christophe; Kemp, E. Helen; Rouvet, Isabelle; Malcus, Christophe; Méritet, Jean-Francois; Lim, Annick; Crow, Yanick J.; Fabien, Nicole; Ménétrier-Caux, Christine; De Villartay, Jean-Pierre; Walzer, Thierry; Belot, Alexandre

    2015-01-01

    Background PRKDC encodes for DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a kinase that forms part of a complex (DNA-dependent protein kinase [DNA-PK]) crucial for DNA double-strand break repair and V(D)J recombination. In mice DNA-PK also interacts with the transcription factor autoimmune regulator (AIRE) to promote central T-cell tolerance. Objective We sought to understand the causes of an inflammatory disease with granuloma and autoimmunity associated with decreasing T- and B-cell counts over time that had been diagnosed in 2 unrelated patients. Methods Genetic, molecular, and functional analyses were performed to characterize an inflammatory disease evocative of a combined immunodeficiency. Results We identified PRKDC mutations in both patients. These patients exhibited a defect in DNA double-strand break repair and V(D)J recombination. Whole-blood mRNA analysis revealed a strong interferon signature. On activation, memory T cells displayed a skewed cytokine response typical of TH2 and TH1 but not TH17. Moreover, mutated DNA-PKcs did not promote AIRE-dependent transcription of peripheral tissue antigens in vitro. The latter defect correlated in vivo with production of anti–calcium-sensing receptor autoantibodies, which are typically found in AIRE-deficient patients. In addition, 9 months after bone marrow transplantation, patient 1 had Hashimoto thyroiditis, suggesting that organ-specific autoimmunity might be linked to nonhematopoietic cells, such as AIRE-expressing thymic epithelial cells. Conclusion Deficiency of DNA-PKcs, a key AIRE partner, can present as an inflammatory disease with organ-specific autoimmunity, suggesting a role for DNA-PKcs in regulating autoimmune responses and maintaining AIRE-dependent tolerance in human subjects. PMID:25842288

  9. Autoantibodies against MHC class I polypeptide-related sequence A are associated with increased risk of concomitant autoimmune diseases in celiac patients

    PubMed Central

    2014-01-01

    Background Overexpression of autologous proteins can lead to the formation of autoantibodies and autoimmune diseases. MHC class I polypeptide-related sequence A (MICA) is highly expressed in the enterocytes of patients with celiac disease, which arises in response to gluten. The aim of this study was to investigate anti-MICA antibody formation in patients with celiac disease and its association with other autoimmune processes. Methods We tested serum samples from 383 patients with celiac disease, obtained before they took up a gluten-free diet, 428 patients with diverse autoimmune diseases, and 200 controls for anti-MICA antibodies. All samples were also tested for anti-endomysium and anti-transglutaminase antibodies. Results Antibodies against MICA were detected in samples from 41.7% of patients with celiac disease but in only 3.5% of those from controls (P <0.0001) and 8.2% from patients with autoimmune disease (P <0.0001). These antibodies disappeared after the instauration of a gluten-free diet. Anti-MICA antibodies were significantly prevalent in younger patients (P <0.01). Fifty-eight patients with celiac disease (15.1%) presented a concomitant autoimmune disease. Anti-MICA-positive patients had a higher risk of autoimmune disease than MICA antibody-negative patients (P <0.0001; odds ratio = 6.11). The risk was even higher when we also controlled for age (odds ratio = 11.69). Finally, we found that the associated risk of developing additional autoimmune diseases was 16 and 10 times as high in pediatric patients and adults with anti-MICA, respectively, as in those without. Conclusions The development of anti-MICA antibodies could be related to a gluten-containing diet, and seems to be involved in the development of autoimmune diseases in patients with celiac disease, especially younger ones. PMID:24565339

  10. Tenascin‐C Aggravates Autoimmune Myocarditis via Dendritic Cell Activation and Th17 Cell Differentiation

    PubMed Central

    Machino‐Ohtsuka, Tomoko; Tajiri, Kazuko; Kimura, Taizo; Sakai, Satoshi; Sato, Akira; Yoshida, Toshimichi; Hiroe, Michiaki; Yasutomi, Yasuhiro; Aonuma, Kazutaka; Imanaka‐Yoshida, Kyoko

    2014-01-01

    Background Tenascin‐C (TN‐C), an extracellular matrix glycoprotein, appears at several important steps of cardiac development in the embryo, but is sparse in the normal adult heart. TN‐C re‐expresses under pathological conditions including myocarditis, and is closely associated with tissue injury and inflammation in both experimental and clinical settings. However, the pathophysiological role of TN‐C in the development of myocarditis is not clear. We examined how TN‐C affects the initiation of experimental autoimmune myocarditis, immunologically. Methods and Results A model of experimental autoimmune myocarditis was established in BALB/c mice by immunization with murine α‐myosin heavy chains. We found that TN‐C knockout mice were protected from severe myocarditis compared to wild‐type mice. TN‐C induced synthesis of proinflammatory cytokines, including interleukin (IL)‐6, in dendritic cells via activation of a Toll‐like receptor 4, which led to T‐helper (Th)17 cell differentiation and exacerbated the myocardial inflammation. In the transfer experiment, dendritic cells loaded with cardiac myosin peptide acquired the functional capacity to induce myocarditis when stimulated with TN‐C; however, TN‐C‐stimulated dendritic cells generated from Toll‐like receptor 4 knockout mice did not induce myocarditis in recipients. Conclusions Our results demonstrated that TN‐C aggravates autoimmune myocarditis by driving the dendritic cell activation and Th17 differentiation via Toll‐like receptor 4. The blockade of Toll‐like receptor 4‐mediated signaling to inhibit the proinflammatory effects of TN‐C could be a promising therapeutic strategy against autoimmune myocarditis. PMID:25376187

  11. Galectin isolated from parasite inhibits remission of experimental autoimmune encephalomyelitis by up-regulating autoantibody

    PubMed Central

    Bing, S J; Ha, D; Ahn, G; Cho, J; Kim, A; Park, S K; Yu, H S; Jee, Y

    2015-01-01

    Recently, parasite infections or parasite-derived products have been suggested as a therapeutic strategy with suppression of immunopathology, which involves the induction of regulatory T cells or/and T helper type 2 (Th2) responses. In a recent study, researchers reported that constructed recombinant galectin (rTl-gal) isolated from an adult worm of the gastrointestinal nematode parasite Toxascaris leonina attenuated clinical symptoms of inflammatory bowel disease in mice treated with dextran sulphate sodium. Noting the role of rTl-gal in inflammatory disease, we attempted to investigate the effect of the parasite via its rTl-gal on neuronal autoimmune disease using experimental autoimmune encephalomyelitis (EAE), a mouse inflammatory and demyelinating autoimmune disease model of human multiple sclerosis. In this model, rTl-gal-treated experimental autoimmune encephalomyelitis (EAE) mice failed to recover after the peak of the disease, leading to persistent central nervous system (CNS) damage, such as demyelination, gliosis and axonal damage. Further, rTl-gal-treated EAE mice markedly increased the number of CD45R/B220+ B cells in both infiltrated inflammation and the periphery, along with the increased production of autoantibody [anti-myelin oligodendrocyte glycoprotein (MOG)35–55] in serum at chronic stage. Upon antigen restimulation, rTl-gal treatment affected the release of overall cytokines, especially interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Our results suggest that galectin isolated from a gastrointestinal parasite can deliver a harmful effect to EAE contrary to its beneficial effect on inflammatory bowel disease. PMID:25619397

  12. Genetic susceptibility to autoimmune liver disease.

    PubMed

    Mattner, Jochen

    2011-01-27

    Autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are considered as putative autoimmune diseases of the liver. Whereas strong evidence that bacterial infection may trigger PBC exists, the etiologies for PSC and AIH remain unknown. Although there have been significant discoveries of genetic polymorphisms that may underlie the susceptibility to these liver diseases, their associations with environmental triggers and the subsequent implications have been difficult to elucidate. While single nucleotide polymorphisms within the negative costimulatory molecule cytotoxic T lymphocyte antigen 4 (CTLA-4) have been suggested as genetic susceptibility factors for all three disorders, we discuss the implications of CTLA-4 susceptibility alleles mainly in the context of PBC, where Novosphingobium aromaticivorans, an ubiquitous alphaproteobacterium, has recently been specifically associated with the pathogenesis of this devastating liver disease. Ultimately, the discovery of infectious triggers of PBC may expand the concept of genetic susceptibility in immune-mediated liver diseases from the concept of aberrant immune responses against self-antigens to insufficient and/or inappropriate immunological defense mechanisms allowing microbes to cross natural barriers, establish infection and damage respective target organs. PMID:21307981

  13. Autoimmune pancreatitis can develop into chronic pancreatitis

    PubMed Central

    2014-01-01

    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

  14. Cacao polyphenols ameliorate autoimmune myocarditis in mice.

    PubMed

    Zempo, Hirofumi; Suzuki, Jun-Ichi; Watanabe, Ryo; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki

    2016-04-01

    Myocarditis is a clinically severe disease; however, no effective treatment has been established. The aim of this study was to determine whether cacao bean (Theobroma cacao) polyphenols ameliorate autoimmune myocarditis. We used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. Mice with induced EAM were treated with a cacao polyphenol extract (CPE, n=12) or vehicle (n=12). On day 21, hearts were harvested and analyzed. Elevated heart weight to body weight and fibrotic area ratios as well as high cardiac cell infiltration were observed in the vehicle-treated EAM mice. However, these increases were significantly suppressed in the CPE-treated mice. Reverse transcriptase-PCR revealed that mRNA expressions of interleukin (Il)-1β, Il-6, E-selectin, vascular cell adhesion molecule-1 and collagen type 1 were lower in the CPE group compared with the vehicle group. The mRNA expressions of nicotinamide adenine dinucleotide phosphate-oxidase (Nox)2 and Nox4 were increased in the vehicle-treated EAM hearts, although CPE treatment did not significantly suppress the transcription levels. However, compared with vehicle treatment of EAM hearts, CPE treatment significantly suppressed hydrogen peroxide concentrations. Cardiac myeloperoxidase activity, the intensity of dihydroethidium staining and the phosphorylation of nuclear factor-κB p65 were also lower in the CPE group compared with the vehicle group. Our data suggest that CPE ameliorates EAM in mice. CPE is a promising dietary supplement to suppress cardiovascular inflammation and oxidative stress. PMID:26657007

  15. Novel Therapies for Thyroid Autoimmune Diseases.

    PubMed

    Fallahi, Poupak; Ferrari, Silvia Martina; Elia, Giusy; Nasini, Francesco; Colaci, Michele; Giuggioli, Dilia; Vita, Roberto; Benvenga, Salvatore; Ferri, Clodoveo; Antonelli, Alessandro

    2016-06-01

    C-X-C chemokine receptor (CXCR)3 and its interferon(IFN)γ-dependent chemokines (CXCL10, CXCL9, CXCL11) are implicated in the immune-pathogenesis of autoimmune thyroiditis (AT), Graves disease (GD) and Graves Ophthalmopathy (GO). In tissue, recruited Th1 lymphocytes produce IFNγ, enhancing the tissue secretion of IFNγ-inducible chemokines, initiating and perpetuating the autoimmune process. Patients with AT (with hypothyroidism), and with GO and GD, particularly in the active phase, have high IFNγ-inducible chemokines. Peroxisome proliferator-activated receptor (PPAR)γ or -α agonists and methimazole exert an immune-modulation on CXCR3 chemokines in AT, GD and GO. Other studies are ongoing to evaluate new molecules acting as antagonists of CXCR3, or blocking CXCL10, in Hashimoto thyroiditis (HT), GD and GO. Recently, novel molecules targeting the various agents involved in the pathogenesis of GO, such as rituximab, have been proposed as an alternative to corticosteroids. However, randomized and controlled studies are needed to generalize these interesting results. PMID:26900630

  16. Regulatory T cells in spontaneous autoimmune encephalomyelitis.

    PubMed

    Furtado, G C; Olivares-Villagómez, D; Curotto de Lafaille, M A; Wensky, A K; Latkowski, J A; Lafaille, J J

    2001-08-01

    Spontaneous experimental autoimmune encephalomyelitis (EAE) develops in 100% of mice harboring a monoclonal myelin basic protein (MBP)-specific CD4+ alphabeta T-cell repertoire. Monoclonality of the alphabeta T-cell repertoire can be achieved by crossing MBP-specific T-cell receptor (TCR) transgenic mice with either RAG-/- mice or TCR alpha-/-/TCR beta-/- double knockout mice. Spontaneous EAE can be prevented by a single administration of purified CD4+ splenocytes or thymocytes obtained from wild-type syngeneic mice. The regulatory T cells (T-reg) that protect from spontaneous EAE need not express the CD25 marker, as effective protection can be attained with populations depleted of CD25+ T cells. Although the specificity of the regulatory T cells is important for their generation or regulatory function, T cells that protect from spontaneous EAE can have a diverse TCR alpha and beta chain composition. T-reg cells expand poorly in vivo, and appear to be long lived. Finally, precursors for T-reg are present in fetal liver as well as in the bone marrow of aging mice. We propose that protection of healthy individuals from autoimmune diseases involves several layers of regulation, which consist of CD4+CD25+ regulatory T cells, CD4+CD25- T-reg cells, and anti-TCR T cells, with each layer potentially operating at different stages of T-helper cell-mediated immune responses. PMID:11722629

  17. Immunomodulation of Autoimmune Arthritis by Herbal CAM

    PubMed Central

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

    2011-01-01

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

  18. Vitamin D, steroid hormones, and autoimmunity.

    PubMed

    Cutolo, Maurizio; Paolino, Sabrina; Sulli, Alberto; Smith, Vanessa; Pizzorni, Carmen; Seriolo, Bruno

    2014-05-01

    The endogenous serum metabolite of vitamin D (calcitriol, 1,25(OH)2 D3 ) is considered a true steroid hormone (D hormone), and like glucocorticoids (GCs) and gonadal hormones, may exert several immunomodulatory activities. Serum vitamin D deficiency (25(OH) D), and therefore reduced 1,25(OH)2 D3 availability, is considered a risk factor for several chronic/inflammatory or autoimmune conditions, including infectious diseases, type 1 diabetes, multiple sclerosis, and especially autoimmune rheumatic diseases (ARD). In ARD in particular, 1,25(OH)2 D3 regulates both innate and adaptive immunity, potentiating the innate response (antimicrobial activity) but reducing adaptive immunity (antigen presentation, T and B cell activities). Regarding a possible synergism between vitamin D and GCs, several studies show that 1,25(OH)2 D3 has significant additive effects on dexamethasone-mediated inhibition of human lymphocyte and monocyte proliferation. Conversely, vitamin D deficiency seems to play a role in increasing autoantibody production by B cells, and seasonal vitamin D declines may trigger flares in ARD, as recently shown. Finally, 1,25(OH)2 D3 seems to reduce aromatase activity and limit the negative effects related to increased peripheral estrogen metabolism (cell proliferation, B cell overactivity). PMID:24739090

  19. Screening tests for autoimmune-related immunotoxicity.

    PubMed Central

    Pieters, R; Albers, R

    1999-01-01

    A large number of chemicals induce or exacerbate autoimmune-like diseases in man. Because of the complexity of processes involved, these adverse effects are often if not always missed in standard toxicity testing. To date no validated and generally applicable predictive animal model exists and only a few chemicals have actually been shown to induce adverse autoimmune effects in certain animals. The popliteal lymph node assay (PLNA) is a very promising animal test to (pre)screen for systemic immunosensitizing, including autoimmunogenic potential. This review describes the essentials of the various PLNAs against the background of current understanding of chemically induced systemic immunostimulation. The most simple primary PLNA measures enlargement of the popliteal lymph node 6-8 days after subcutaneous injection of a chemical into the footpad. The primary PLNA can distinguish between immunostimulating (both sensitizers and irritants) and innocent chemicals but does not assess the involvement of T cells or immunosensitization. For this, but also for elucidation of relevant mechanisms, detection of anamnestic responses in secondary PLNAs or responses to reporter antigens in the modified PLNA are suitable. To date over 100 compounds (drugs and environmental pollutants) have been tested, and results show a good correlation with reported immunostimulating (both autoimmunogenic and allergic) potential. Importantly, no false-negative chemicals were detected if metabolism was considered. The various types of the PLNA, but in particular the secondary and modified PLNAs, await extensive validation before they can be recommended as a standard test for autoimmunogenic potential. Images Figure 2 Figure 3 PMID:10502529

  20. Autoimmune Hepatitis in Hawai'i.

    PubMed

    Kim, Tanner I; Kagihara, Jaclyn E; Tsai, Naoky C S; Roytman, Marina M

    2015-08-01

    Autoimmune Hepatitis (AIH) is a poorly understood disease. There has been a paucity of reports on the epidemiology and clinical course of AIH in multiethnic populations. The aim of this study is to examine the clinical and serologic features of AIH in the multiethnic population of Hawai'i. This was a retrospective, cross-sectional study of a cohort of patients seen between 2010-2013 in a tertiary referral center in Hawai'i. All 32 patients were diagnosed according to International Autoimmune Hepatitis Group (IAIHG) criteria. The mean (SD) age of diagnosis was 49.4 (17.5) years, 75% of patients were female, 72% were Asian, 19% were Caucasian, 6% were Pacific Islander, and 3% were African American. When compared to Caucasians, Asians had lower transaminase levels and international normalized ratio (INR), and were more likely to have anti-nuclear antibody (ANA) seropositivity at presentation. Asians were also older at diagnosis and more likely to achieve complete or partial remission. Patients diagnosed before the age of 40 had higher levels of total bilirubin at presentation compared to those diagnosed after the age of 40. No significant differences were observed between genders. Asian patients with type I AIH present later in life with more favorable laboratory values, and have a superior treatment response compared to Caucasians. Diagnosis before the age of 40 is associated with less favorable laboratory values at diagnosis. Further studies are necessary to validate these findings and determine the reason for the ethnic differences. PMID:26279964

  1. Autoimmune pathogenesis in dengue virus infection.

    PubMed

    Lin, Chiou-Feng; Wan, Shu-Wen; Cheng, Hsien-Jen; Lei, Huan-Yao; Lin, Yee-Shin

    2006-01-01

    The pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) caused by dengue virus (DV) infection remain unresolved. Patients with DHF/DSS are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and hepatomegaly. In addition to the effect of virus load and virus variation, abnormal immune responses of the host after DV infection may also account for the progression of DHF/DSS. Actually, viral autoimmunity is involved in the pathogenesis of numerous viral infections, such as human immunodeficiency virus, human hepatitis C virus, human cytomegalovirus, herpes simplex virus, Epstein- Barr virus, and DV. In this review, we discuss the implications of autoimmunity in dengue pathogenesis. Antibodies directed against DV nonstructural protein 1 (NS1) showed cross-reactivity with human platelets and endothelial cells, which lead to platelet and endothelial cell damage and inflammatory activation. Based on these findings, we hypothesize that anti-DV NS1 is involved in the pathogenesis of DF and DHF/DSS, and this may provide important information in dengue vaccine development. PMID:16817755

  2. Autoimmunity in chronic urticaria and urticarial vasculitis.

    PubMed

    Napoli, D C; Freeman, T M

    2001-07-01

    In contrast to acute urticaria, etiology cannot be identified in most cases of chronic urticaria. Recent evidence suggests that a subset of patients with chronic urticaria may have an autoimmune basis for their condition. The demonstration of antithyroid autoantibodies in some patients with chronic idiopathic urticaria (CIU) provides support for an association. However, the discovery of a positive skin test response to intradermal injection of autologous serum in as many as 60% of patients with CIU led to the identification of autoantibodies to IgE and the alpha-chain of the high-affinity IgE receptor, Fc epsilon RI alpha. Additional studies have demonstrated that some of these autoantibodies are capable of releasing histamine from donor basophils and mast cells. This article reviews the literature that addresses a possible autoimmune etiology in a subset of patients with CIU. Urticarial vasculitis is differentiated from chronic urticaria based on clinical features and biopsy findings of leukocytoclastic vasculitis. Most cases of urticarial vasculitis are secondary to an underlying systemic disease. The presence of autoantibodies has also been demonstrated in a subset of patients with primary urticarial vasculitis. This article briefly reviews some of this data. PMID:11892055

  3. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    PubMed Central

    Jara, Luis J.; Navarro, Carmen; Medina, Gabriela; Vera-Lastra, Olga; Blanco, Francisco

    2006-01-01

    The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.Autoimmune rheumatic diseases (ARD) are characterized by aberrant production of pro-inflammatory cytokines, which are a potent activator of the HPA axis. In consequence, high levels of pro-inflammatory hormones such as estrogens and prolactin, and low levels of glucocorticoids, an anti-inflammatory hormone, have been described in the active phase of ARD. In addition, high levels of pro-inflammatory hormones and cytokines have also been frequently detected in organ involvement of patients with ARD, suggesting an abnormal local neuroendocrine immune interaction. There is evidence that hormonal changes may appear before the symptomatic phase of the disease. Therefore, it is possible that a pro-inflammatory hormone favors the rupture of tolerance, which is a key feature of autoimmune diseases. The interactions between the immune-neuroendocrine system have a major impact on our understanding of the pathogenic mechanisms, diagnosis and therapy of ARD. PMID:17162354

  4. Selected Aspects in the Pathogenesis of Autoimmune Diseases

    PubMed Central

    Nagy, György; Huszthy, Peter C.; Fossum, Even; Konttinen, Yrjö; Nakken, Britt; Szodoray, Peter

    2015-01-01

    Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies. PMID:26300591

  5. Gender differences in autoimmunity associated with exposure to environmental factors

    PubMed Central

    Pollard, K. Michael

    2011-01-01

    Autoimmunity is thought to result from a combination of genetics, environmental triggers, and stochastic events. Gender is also a significant risk factor with many diseases exhibiting a female bias. Although the role of environmental triggers, especially medications, in eliciting autoimmunity is well established less is known about the interplay between gender, the environment and autoimmunity. This review examines the contribution of gender in autoimmunity induced by selected chemical, physical and biological agents in humans and animal models. Epidemiological studies reveal that environmental factors can be associated with a gender bias in human autoimmunity. However many studies show that the increased risk of autoimmunity is often influenced by occupational exposure or other gender biased activities. Animal studies, although often prejudiced by the exclusive use of female animals, reveal that gender bias can be strain specific suggesting an interaction between sex chromosome complement and background genes. This observation has important implications because it argues that within a gender biased disease there may be individuals in which gender does not contribute to autoimmunity. Exposure to environmental factors, which encompasses everything around us, adds an additional layer of complexity. Understanding how the environment influences the relationship between sex chromosome complement and innate and adaptive immune responses will be essential in determining the role of gender in environmentally-induced autoimmunity. PMID:22137891

  6. IL-2: a two-faced master regulator of autoimmunity.

    PubMed

    Sharma, Rahul; Fu, Shu Man; Ju, Shyr-Te

    2011-03-01

    CD4(+) T-cell (Th) cytokines provide important regulatory and effector functions of T-cells. Among them, IL-2 plays a unique role. IL-2 is required for the generation and maintenance of regulatory T-cells (Treg) to provide lifelong protection from autoimmune disease. Whether IL-2 is also required for autoimmune disease development is less clear as Il2(-/)(-) mice themselves spontaneously develop multi-organ inflammation (MOI). In this communication, we discuss evidence that support the thesis that IL-2 is required for the development of autoimmune response, although some aspects of autoimmune response are not regulated by IL-2. Potential IL-2-dependent mechanisms operating at specific stages of the inflammation process are presented. The interplays among Treg, IL-2, autoimmune response and adaptive immunity are discussed. Overall, available information indicates that IL-2 is a two-faced master regulator of autoimmunity: one to prevent autoimmunity while the other promotes autoimmune response. The latter is an unfortunate consequence of IL-2 function that is used to promote the adaptive immune response against foreign antigens and pathogens. PMID:21282039

  7. Specific autoantigens in experimental autoimmunity-associated atherosclerosis.

    PubMed

    Merched, Aksam J; Daret, Danièle; Li, Lan; Franzl, Nathalie; Sauvage-Merched, Maria

    2016-06-01

    Higher cardiovascular morbidity in patients with a wide range of autoimmune diseases highlights the importance of autoimmunity in promoting atherosclerosis. Our purpose was to investigate the mechanisms of accelerated atherosclerosis and identified vascular autoantigens targeted by autoimmunity. We created a mouse model of autoimmunity-associated atherosclerosis by transplanting bone marrow from FcγRIIB knockout (FcRIIB(-/-)) mice into LDL receptor knockout mice. We characterized the cellular and molecular mechanisms of atherogenesis and identified specific aortic autoantigens using serologic proteomic studies. En face lesion area analysis showed more aggressive atherosclerosis in autoimmune mice compared with control mice (0.64 ± 0.12 vs 0.32 ± 0.05 mm(2); P < 0.05, respectively). At the cellular level, FcRIIB(-/-) macrophages showed significant reduction (46-72%) in phagocytic capabilities. Proteomic analysis revealed circulating autoantibodies in autoimmune mice that targeted 25 atherosclerotic lesion proteins, including essential components of adhesion complex, cytoskeleton, and extracellular matrix, and proteins involved in critical functions and pathways. Microscopic examination of atherosclerotic plaques revealed essential colocalization of autoantibodies with endothelial cells, their adherence to basement membranes, the internal elastica lamina, and necrotic cores. The new vascular autoimmunosome may be a useful target for diagnostic and immunotherapeutic interventions in autoimmunity-associated diseases that have accelerated atherosclerosis.-Merched, A. J., Daret, D., Li, L., Franzl, N., Sauvage-Merched, M. Specific autoantigens in experimental autoimmunity-associated atherosclerosis. PMID:26891734

  8. Introducing Polyautoimmunity: Secondary Autoimmune Diseases No Longer Exist

    PubMed Central

    Rojas-Villarraga, Adriana; Amaya-Amaya, Jenny; Rodriguez-Rodriguez, Alberto; Mantilla, Rubén D.; Anaya, Juan-Manuel

    2012-01-01

    Similar pathophysiological mechanisms within autoimmune diseases have stimulated searches for common genetic roots. Polyautoimmunity is defined as the presence of more than one autoimmune disease in a single patient. When three or more autoimmune diseases coexist, this condition is called multiple autoimmune syndrome (MAS). We analyzed the presence of polyautoimmunity in 1,083 patients belonging to four autoimmune disease cohorts. Polyautoimmunity was observed in 373 patients (34.4%). Autoimmune thyroid disease (AITD) and Sjögren's syndrome (SS) were the most frequent diseases encountered. Factors significantly associated with polyautoimmunity were female gender and familial autoimmunity. Through a systematic literature review, an updated search was done for all MAS cases (January 2006–September 2011). There were 142 articles retrieved corresponding to 226 cases. Next, we performed a clustering analysis in which AITD followed by systemic lupus erythematosus and SS were the most hierarchical diseases encountered. Our results indicate that coexistence of autoimmune diseases is not uncommon and follows a grouping pattern. Polyautoimmunity is the term proposed for this association of disorders, which encompasses the concept of a common origin for these diseases. PMID:22454759

  9. Applications of Next-generation Sequencing in Systemic Autoimmune Diseases

    PubMed Central

    Ma, Yiyangzi; Shi, Na; Li, Mengtao; Chen, Fei; Niu, Haitao

    2015-01-01

    Systemic autoimmune diseases are a group of heterogeneous disorders caused by both genetic and environmental factors. Although numerous causal genes have been identified by genome-wide association studies (GWAS), these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogenesis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body’s immune system and is likely related to genetic mutations in systemic autoimmune diseases. Next-generation sequencing (NGS) technology, with high-throughput capacity and accuracy, provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases. PMID:26432094

  10. Nucleic acid recognizing Toll-like receptors and autoimmunity.

    PubMed

    von Landenberg, Philipp; Bauer, Stefan

    2007-12-01

    The understanding of autoimmune diseases experienced an impressive boost since the Toll-like receptors (TLRs) have been identified as possible key players in autoimmune pathophysiology. Although these receptors recognize a variety of structures derived from viruses, bacteria, and fungi leading to subsequent initiation of the relevant immune responses, recent data support the idea that TLRs are crucial in the induction and perpetuation of certain autoimmune diseases, especially the systemic lupus erythematosus (SLE). In this review, we will summarize recent data on involvement of TLRs in the development of autoimmune diseases. We will focus on TLRs 7, 8, and 9 that were originally identified as receptors specific for bacterial and viral RNA/DNA, but more recent in vitro and in vivo studies have linked these receptors to the detection of host RNA, DNA, and RNA-associated or DNA-associated proteins in the context of autoimmunity. PMID:18060756

  11. Recurrence of autoimmune liver diseases after liver transplantation

    PubMed Central

    Faisal, Nabiha; Renner, Eberhard L

    2015-01-01

    Liver transplantation (LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but not for primary sclerosing cholangitis (PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease (AIH, PBC, PSC) following LT. PMID:26689244

  12. Reactive oxygen species in organ-specific autoimmunity.

    PubMed

    Di Dalmazi, Giulia; Hirshberg, Jason; Lyle, Daniel; Freij, Joudeh B; Caturegli, Patrizio

    2016-12-01

    Reactive oxygen species (ROS) have been extensively studied in the induction of inflammation and tissue damage, especially as it relates to aging. In more recent years, ROS have been implicated in the pathogenesis of autoimmune diseases. Here, ROS accumulation leads to apoptosis and autoantigen structural changes that result in novel specificities. ROS have been implicated not only in the initiation of the autoimmune response but also in its amplification and spreading to novel epitopes, through the unmasking of cryptic determinants. This review will examine the contribution of ROS to the pathogenesis of four organ specific autoimmune diseases (Hashimoto thyroiditis, inflammatory bowel disease, multiple sclerosis, and vitiligo), and compare it to that of a better characterized systemic autoimmune disease (rheumatoid arthritis). It will also discuss tobacco smoking as an environmental factor endowed with both pro-oxidant and anti-oxidant properties, thus capable of differentially modulating the autoimmune response. PMID:27491295

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

    PubMed Central

    Armangue, Thaís; Leypoldt, Frank; Dalmau, Josep

    2014-01-01

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

  14. Role of Tumor Necrosis Factor Superfamily in Neuroinflammation and Autoimmunity

    PubMed Central

    Sonar, Sandip; Lal, Girdhari

    2015-01-01

    Tumor necrosis factor superfamily (TNFSF) molecules play an important role in the activation, proliferation, differentiation, and migration of immune cells into the central nervous system (CNS). Several TNF superfamily molecules are known to control alloimmunity, autoimmunity, and immunity. Development of transgenic and gene knockout animals, and monoclonal antibodies against TNFSF molecules have increased our understanding of individual receptor–ligand interactions, and their intracellular signaling during homeostasis and neuroinflammation. A strong clinical association has been observed between TNFSF members and CNS autoimmunity such as multiple sclerosis and also in its animal model experimental autoimmune encephalomyelitis. Therefore, they are promising targets for alternative therapeutic options to control autoimmunity. Although, TNFSF ligands are widely distributed and have diverse functions, we have restricted the discussions in this review to TNFSF receptor–ligand interactions and their role in the pathogenesis of neuroinflammation and CNS autoimmunity. PMID:26257732

  15. [Three cases of childhood-onset autoimmune pancreatitis].

    PubMed

    Murata, Shinya; Yoden, Atsushi; Aomatsu, Tomoki; Inoue, Keisuke; Tamai, Hiroshi

    2014-08-01

    Here we present 3 cases of childhood-onset autoimmune pancreatitis: 2 cases in boys aged 4 and 16 years, diagnosed with ulcerative colitis; 1 case in a previously healthy 10-year-old boy. All 3 boys presented with abdominal pain associated with elevated pancreatic enzyme levels. Immunoglobulin G4 levels were elevated only in the 16-year-old boy. However, pancreatic enlargement together with narrowing of the main pancreatic duct was evident on computed tomography in all 3 cases. Autoimmune pancreatitis is an uncommon disease in childhood, and only 3 cases affecting patients under 17 years of age have previously been reported in Japan. Autoimmune pancreatitis may be latent in children with pancreatitis who have chronic or intermittent abdominal symptoms. In addition, it is necessary to recognize autoimmune pancreatitis as a complication of pediatric inflammatory bowel disease. The clinical features of pediatric autoimmune pancreatitis remain unclear, and an accumulation of cases is necessary. PMID:25100354

  16. Transfer of hematopoietic stem cells encoding autoantigen prevents autoimmune diabetes.

    PubMed

    Steptoe, Raymond J; Ritchie, Janine M; Harrison, Leonard C

    2003-05-01

    Bone marrow or hematopoietic stem cell transplantation is a potential treatment for autoimmune disease. The clinical application of this approach is, however, limited by the risks associated with allogeneic transplantation. In contrast, syngeneic transplantation would be safe and have wide clinical application. Because T cell tolerance can be induced by presenting antigen on resting antigen-presenting cells (APCs), we reasoned that hematopoietic stem cells engineered to express autoantigen in resting APCs could be used to prevent autoimmune disease. Proinsulin is a major autoantigen associated with pancreatic beta cell destruction in humans with type 1 diabetes (T1D) and in autoimmune NOD mice. Here, we demonstrate that syngeneic transplantation of hematopoietic stem cells encoding proinsulin transgenically targeted to APCs totally prevents the development of spontaneous autoimmune diabetes in NOD mice. This antigen-specific immunotherapeutic strategy could be applied to prevent T1D and other autoimmune diseases in humans. PMID:12727927

  17. Applications of Next-generation Sequencing in Systemic Autoimmune Diseases.

    PubMed

    Ma, Yiyangzi; Shi, Na; Li, Mengtao; Chen, Fei; Niu, Haitao

    2015-08-01

    Systemic autoimmune diseases are a group of heterogeneous disorders caused by both genetic and environmental factors. Although numerous causal genes have been identified by genome-wide association studies (GWAS), these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogenesis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body's immune system and is likely related to genetic mutations in systemic autoimmune diseases. Next-generation sequencing (NGS) technology, with high-throughput capacity and accuracy, provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases. PMID:26432094

  18. Autoimmunity: from black water fever to regulatory function.

    PubMed

    Chang, Christopher

    2014-01-01

    Autoimmunity is a field that has only been around for a little over a century. Initially, it was thought that autoimmunity could not happen, that the body would never turn on itself (i.e. "horror autotoxicus"). It was only around the First World War that autoimmunity was recognized as the pathogenesis of various diseases, including rheumatoid arthritis. The discovery of Compound E led to successful treatment of patients with autoimmune diseases, but it was not till later that the adverse effects of this class of drugs were elucidated. The "modern" age of autoimmunity began around 1945 with the description of blackwater fever, and most of the subsequent research on hemolytic anemia and the role of an autoantibody in its pathogenesis led to a description of the anti-globulin reaction. The lupus erythematous (LE) cell was recognized in the mid-1940s by Hargreaves. His research carried on into the 1960s. Rheumatoid factor was also first described in the 1940s as yet another serum factor with activity against globulin-coated sheep red blood cells. The concept of autoimmunity really gained a foothold in the 1950s, when autoimmune thyroid disease and idiopathic thrombocytopenia were first described. Much has happened since then, and our understanding of autoimmunity has evolved now to include mechanisms of apoptosis, signaling pathway derangements, and the discovery of subsets of T cells with regulatory activity. The modern day study of autoimmunity is a fascinating area of research, and full understanding of the pathogenesis of autoimmune diseases is far from being completely elucidated. PMID:24491820

  19. Alpha-tocopherol ameliorates experimental autoimmune encephalomyelitis through the regulation of Th1 cells

    PubMed Central

    Xue, Haikuo; Ren, Huijun; Zhang, Lei; Sun, Xiaoxu; Wang, Wanhai; Zhang, Shijie; Zhao, Junwei; Ming, Liang

    2016-01-01

    Objective(s): Multiple sclerosis (MS) is a serious neurological autoimmune disease, it commonly affects young adults. Vitamin E (Vit E) is an important component of human diet with antioxidant activity, which protects the body’s biological systems. In order to assess the effect of Vit E treatment on this autoimmune disease, we established experimental autoimmune encephalomyelitis (EAE), the animal model of MS, and treated EAE with α-tocopherol (AT) which is the main content of Vit E. Materials and Methods: Twenty C57BL/6 adult female mice were used and divided into two groups randomly. EAE was induced with myelin oligodendrocyte glycoprotein (MOG), and one group was treated with AT, at a dose of 100 mg/kg on the 3th day post-immunization with MOG, the other group was treated with 1% alcohol. Mice were euthanized on day 14, post-immunization, spleens were removed for assessing splenocytes proliferation and cytokine profile, and spinal cords were dissected to assess the infiltration of inflammatory cells in spinal cord. Results: AT was able to attenuate the severity of EAE and delay the disease progression. H&E staining and fast blue staining indicated that AT reduced the inflammation and the demyelination reaction in the spinal cord. Treatment with AT significantly decreased the proliferation of splenocytes. AT also inhibited the production of IFN-γ (Th1 cytokine), though the other cytokines were only affected slightly. Conclusion: According to the results, AT ameliorated EAE, through suppressing the proliferation of T cells and the Th1 response. AT may be used as a potential treatment for MS. PMID:27403263

  20. Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity.

    PubMed

    Paterson, Alison M; Lovitch, Scott B; Sage, Peter T; Juneja, Vikram R; Lee, Youjin; Trombley, Justin D; Arancibia-Cárcamo, Carolina V; Sobel, Raymond A; Rudensky, Alexander Y; Kuchroo, Vijay K; Freeman, Gordon J; Sharpe, Arlene H

    2015-09-21

    Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of T cell responses. Germline Ctla4 deficiency is lethal, making investigation of the function of CTLA-4 on mature T cells challenging. To elucidate the function of CTLA-4 on mature T cells, we have conditionally ablated Ctla4 in adult mice. We show that, in contrast to germline knockout mice, deletion of Ctla4 during adulthood does not precipitate systemic autoimmunity, but surprisingly confers protection from experimental autoimmune encephalomyelitis (EAE) and does not lead to increased resistance to MC38 tumors. Deletion of Ctla4 during adulthood was accompanied by activation and expansion of both conventional CD4(+)Foxp3(-) (T conv) and regulatory Foxp3(+) (T reg cells) T cell subsets; however, deletion of CTLA-4 on T reg cells was necessary and sufficient for protection from EAE. CTLA-4 deleted T reg cells remained functionally suppressive. Deletion of Ctla4 on T reg cells alone or on all adult T cells led to major changes in the Ctla4 sufficient T conv cell compartment, including up-regulation of immunoinhibitory molecules IL-10, LAG-3 and PD-1, thereby providing a compensatory immunosuppressive mechanism. Collectively, our findings point to a profound role for CTLA-4 on T reg cells in limiting their peripheral expansion and activation, thereby regulating the phenotype and function of T conv cells. PMID:26371185