Genetics Home Reference: immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome

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... Health Conditions IPEX syndrome Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome Printable PDF Open All Close All ... expand/collapse boxes. Description Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome primarily affects males and is ...

A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies.

PubMed

McAllister, Brian P; Williams, Emmanuelle; Clarke, Kofi

2018-06-02

Celiac disease is a complex immune-mediated gluten-sensitive enteropathy with protean clinical manifestations. It is manifest in genetically predisposed individuals who ingest gluten in varying amounts. In broad terms, it is thought to affect 1% of the population in the USA. More specifically, the prevalence increases drastically from 1:133 in patients not-at-risk, to 1:56 in symptomatic patients, to 1:39 in patients with a second-degree relative with the diagnosis, and to 1:22 in patients with a first-degree relative with the diagnosis. It may be associated with several immune-mediated phenomena, autoimmune diseases, and complicated by vitamin and other trace element deficiencies, bone disease, and malignancy. Our understanding of celiac disease has evolved rapidly over the past two decades. This has led to several lines of enquiry on the condition and potential treatment options. More recently, several entities including gluten intolerance, non-celiac gluten sensitivity, and seronegative celiac disease have been described. These conditions are distinct from allergies or intolerance to wheat or wheat products. There are challenges in defining some of these entities since a large number of patients self-report these conditions. The absence of confirmatory diagnostic tests poses an added dilemma in distinguishing these entities. The differences in spectrum of symptoms and highlights of the variability between the pediatric and adult populations have been studied in some detail. The role of screening for celiac disease is examined in both the general population and "at risk" populations. Diagnostic strategies including the best available serologic testing, utility of HLA haplotypes DQ2 and DQ8 which are seen in over 90% of patients with celiac disease as compared with approximately 40% of the general population, and endoscopic evaluation are also reviewed. Comprehensive nutritional management after diagnosis is key to sustained health in patients with celiac disease

Protein-Losing Enteropathy as a Complication of the Ketogenic Diet.

PubMed

Ahn, Won Kee; Park, Soyoung; Kim, Heung Dong

2017-07-01

The ketogenic diet is an effective treatment for the patients with intractable epilepsy, however, the diet therapy can sometimes be discontinued by complications. Protein-losing enteropathy is a rarely reported serious complication of the ketogenic diet. We present a 16-month-old Down syndrome baby with protein-losing enteropathy during the ketogenic diet as a treatment for West syndrome. He suffered from diarrhea, general edema and hypoalbuminemia which were not controlled by conservative care for over 1 month. Esophagogastroduodenoscopy and stool alpha-1 antitrypsin indicated protein-losing enteropathy. Related symptoms were relieved after cessation of the ketogenic diet. Unexplained hypoalbuminemia combined with edema and diarrhea during ketogenic suggests the possibility of protein-losing enteropathy, and proper evaluation is recommended in order to expeditiously detect it and to act accordingly. © Copyright: Yonsei University College of Medicine 2017.

Prevalence of coeliac disease among adult patients with autoimmune hypothyroidism in Jordan.

PubMed

Farahid, O H; Khawaja, N; Shennak, M M; Batieha, A; El-Khateeb, M; Ajlouni, K

2014-02-11

The prevalence of coeliac disease among patients with autoimmune hypothyroidism has not been studied before in Jordan and other Arab countries. A cross-sectional record-based review was made of all adult autoimmune hypothyroidism patients who attended a referral centre in Jordan, during an 8-month period. Coeliac disease in these patients was diagnosed by the attending physician based on positive serological tests for anti-endomysial antibodies IgA and IgG followed by duodenal biopsy to confirm the diagnosis of coeliac disease. Of 914 patients recruited, 117 (12.8%) were seropositive for coeliac disease. Of 87 seropositive patients who underwent duodenal biopsy, 39 had positive histological findings of coeliac disease (44.8%). Extrapolating from these findings the overall rate of coeliac disease among autoimmune hypothyroidism patients was estimated to be 5.7%. In multivariate logistic regression coeliac disease was significantly associated with older age (> 40 years), presence of other autoimmune diseases, vitamin B12 deficiency and anaemia.

Uric acid ameliorates indomethacin-induced enteropathy in mice through its antioxidant activity.

PubMed

Yasutake, Yuichi; Tomita, Kengo; Higashiyama, Masaaki; Furuhashi, Hirotaka; Shirakabe, Kazuhiko; Takajo, Takeshi; Maruta, Koji; Sato, Hirokazu; Narimatsu, Kazuyuki; Yoshikawa, Kenichi; Okada, Yoshikiyo; Kurihara, Chie; Watanabe, Chikako; Komoto, Shunsuke; Nagao, Shigeaki; Matsuo, Hirotaka; Miura, Soichiro; Hokari, Ryota

2017-11-01

Uric acid is excreted from blood into the intestinal lumen, yet the roles of uric acid in intestinal diseases remain to be elucidated. The study aimed to determine whether uric acid could reduce end points associated with nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. A mouse model of NSAID-induced enteropathy was generated by administering indomethacin intraperitoneally to 8-week-old male C57BL/6 mice, and then vehicle or uric acid was administered orally. A group of mice treated with indomethacin was also concurrently administered inosinic acid, a uric acid precursor, and potassium oxonate, an inhibitor of uric acid metabolism, intraperitoneally. For in vitro analysis, Caco-2 cells treated with indomethacin were incubated in the presence or absence of uric acid. Oral administration of uric acid ameliorated NSAID-induced enteropathy in mice even though serum uric acid levels did not increase. Intraperitoneal administration of inosinic acid and potassium oxonate significantly elevated serum uric acid levels and ameliorated NSAID-induced enteropathy in mice. Both oral uric acid treatment and intraperitoneal treatment with inosinic acid and potassium oxonate significantly decreased lipid peroxidation in the ileum of mice with NSAID-induced enteropathy. Treatment with uric acid protected Caco-2 cells from indomethacin-induced oxidative stress, lipid peroxidation, and cytotoxicity. Uric acid within the intestinal lumen and in serum had a protective effect against NSAID-induced enteropathy in mice, through its antioxidant activity. Uric acid could be a promising therapeutic target for NSAID-induced enteropathy. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Olmesartan-induced Enteropathy Manifesting as Wernicke-Korsakoff Syndrome.

PubMed

Uehara, Takanori; Ikusaka, Masatomi; Ohira, Yoshiyuki; Noda, Kazutaka; Suzuki, Shingo; Shikino, Kiyoshi; Kondo, Takeshi; Kajiwara, Hideki; Ikegami, Akiko; Hirota, Yusuke

Cases of sprue-like enteropathy associated with olmesartan have sporadically been encountered since it was first reported in 2012, and their most characteristic manifestation is severe diarrhea. We herein report the first case of sprue-like enteropathy manifesting as Wernicke-Korsakoff syndrome due to vitamin B1 malabsorption with only minimally increased bowel movements. When patients are receiving olmesartan and they complain of nonspecific chronic gastrointestinal symptoms, it is important to consider changing the drugs before any serious malabsorption syndrome develops.

Olmesartan-induced Enteropathy Manifesting as Wernicke-Korsakoff Syndrome

PubMed Central

Uehara, Takanori; Ikusaka, Masatomi; Ohira, Yoshiyuki; Noda, Kazutaka; Suzuki, Shingo; Shikino, Kiyoshi; Kondo, Takeshi; Kajiwara, Hideki; Ikegami, Akiko; Hirota, Yusuke

2016-01-01

Cases of sprue-like enteropathy associated with olmesartan have sporadically been encountered since it was first reported in 2012, and their most characteristic manifestation is severe diarrhea. We herein report the first case of sprue-like enteropathy manifesting as Wernicke-Korsakoff syndrome due to vitamin B1 malabsorption with only minimally increased bowel movements. When patients are receiving olmesartan and they complain of nonspecific chronic gastrointestinal symptoms, it is important to consider changing the drugs before any serious malabsorption syndrome develops. PMID:27980272

Autoimmune hepatitis.

PubMed

Vergani, D; Mieli-Vergani, G

1996-01-01

Autoimmune hepatitis is an inflammatory liver disease in which the immune system is believed to orchestrate an immune attack onto the liver cell. Current knowledge suggests that both T helper 1 (TH1) and TH2 programmes are involved in the generation of the liver damage. Release of TH2 cytokines leads to the production of autoantibodies to the hepatocyte membrane that recruit killer cells. TH1 cytokines induce macrophage activation which contributes to hepatocyte destruction. Patients commonly possess the "autoimmune" HLA A1/B8/DR3 haplotype and a silent gene at the C4A locus with consequent partial deficiency of the complement component C4. Two main types of autoimmune hepatitis are recognised according to the presence of circulating non-organ specific autoantibodies. Patients with smooth muscle antibody and/or antinuclear antibody may be adults or children, while patients with antiliver kidney microsomal type 1 (LKM1) antibody are usually children or very young adults. In both types there is a preponderance of females. LKM1 antibody is also present in a proportion of adult patients, mainly male, with chronic hepatitis C virus infection. This observation originally led to the suggestion that hepatitis C virus may be the cause of this form of autoimmune hepatitis, but several studies have shown that the epitopes target of the LKM1 antibody in autoimmune hepatitis and chronic hepatitis C virus infection differ. Although autoimmune hepatitis responds satisfactorily to immunosuppression in the short term, progression to cirrhosis is frequent. It is hoped that ongoing research will provide a better understanding of the pathogenic mechanisms of liver damage leading to a more effective and specific mode of treatment.

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

In children with autoimmune thyroiditis CTLA4 and FCRL3 genes--but not PTPN22--are overexpressed when compared to adults.

PubMed

Wojciechowska-Durczynska, Katarzyna; Krawczyk-Rusiecka, Kinga; Zygmunt, Arkadiusz; Stawerska, Renata; Lewinski, Andrzej

2016-01-01

Numerous genetic studies revealed several susceptibility genes of autoimmune thyroid diseases (AITD), including CTLA4, PTPN22 and FCRL3. These immune-modulating genes are involved in genetic background of AITD among children and adult patients. However, possible age-related differences in overexpression of these genes remain unclear. The goal of this single centre cohort study was evaluation of expression levels of three (3) genes CTLA4, PTPN22 and FCRL3 in adult patients and children with autoimmune thyroiditis. A total of 47 patients--24 adults (mean age--47.7 years) and 23 children (mean age--12.4 years) with autoimmune thyroiditis were assessed for the level of expression of CTLA4, PTPN22 and FCRL3 genes, utilizing ABI PRISM' 7500 Sequence Detection System (Applied Biosystem, Foster City, CA, USA). The overexpression of PTPN22 (mean RQ = 2.988) and FCRL3 (mean RQ = 2.544) genes were confirmed in adult patients with autoimmune thyroiditis, at the same time the expression level of CTLA4 gene was significantly decreased (mean RQ = 0.899) (p < 0.05). Similar discrepancies were not observed in children with autoimmune thyroiditis in whom overexpression of all three genes--CTLA4, PTPN22 and FCRL3--was observed. Differences in CTLA4 and FCRL3 genes expression levels in patients with autoimmune thyroiditis were found depending on the age, with increased expression levels of CTLA4 (mean RQ = 3.45 1) and FCRL3 (mean RQ = 7.410) in children when compared to adults (p < 0.05) (Mann-Whitney's U-test). There were moderate negative linear correlations between two genes in question (CTLA4 and FCRL3) expression level and patients' age [correlation coefficient (r) = -0.529 (p < 0.0002) and -0.423 (p < 0.0032), respectively; Spearman's rank correlation test]. Our results are consistent with the hypothesis that there are few age-dependent genetic differences as regards autoimmune thyroiditis in adults and children. Accordingly, CTLA4 and FCRL3 genes overexpression may play an

Prevalence of Celiac Disease Autoimmunity Among Adolescents and Young Adults in China.

PubMed

Yuan, Juanli; Zhou, Chunyan; Gao, Jinyan; Li, Jingjing; Yu, Fenglian; Lu, Jun; Li, Xin; Wang, Xiaozhong; Tong, Ping; Wu, Zhihua; Yang, Anshu; Yao, Yonghong; Nadif, Sarah; Shu, Heng; Jiang, Xu; Wu, Yujie; Gilissen, Luud; Chen, Hongbing

2017-10-01

In China, epidemiologic information on celiac disease autoimmunity is scarce and fragmented. We investigated the prevalence of celiac disease autoimmunity in the general Chinese population. In a cross-sectional prospective study, 19,778 undiagnosed Chinese adolescents and young adults (age, 16-25 y) were recruited from consecutive new students who underwent routine physical examinations at 2 universities in Jiangxi, China, from September 2010 through October 2013; the students were from 27 geographic regions in China. All subjects were tested for serum IgG, IgG against deamidated gliadin peptides (IgG anti-DGP), and IgA anti-tissue transglutaminase antibodies (IgA anti-tTG). We also analyzed HLA genotypes in subgroups of participants with different results from tests for serum markers of celiac disease. A total of 434 students (2.19%) tested positive for serum markers for celiac disease (95% confidence interval [CI], 1.99%-2.41%), 0.36% of the students tested positive for anti-tTG IgA (95% CI, 0.28%-0.46%), and 1.88% tested positive for anti-DGP IgG (95% CI, 1.70%-2.09%). The prevalence of celiac disease autoimmunity (positive results in assays for anti-tTG IgA and anti-DGP-IgG) was 0.06% (95% CI, 0.03%-0.10%). Celiac disease autoimmunity was associated with the consumption of wheat and female sex. The prevalence in the Shandong province in north China, where wheat is a staple in the diet, was 0.76% (95% CI, 0.21%-1.95%). The frequencies of the HLA-DQ2/-DQ8 genotypes associated with celiac disease were higher in subjects with celiac disease autoimmunity, based on detection of both serum markers, than in subjects with positive results from a single test (P < .01). All subjects with positive results from both assays carried the HLA-DQ2 genotype. Approximately 2% of adolescents or young adults in China had positive results from assays for serum markers for celiac disease. The prevalence of celiac disease autoimmunity in the Shandong province in north China, where

Anterior hypopituitarism is rare and autoimmune disease is common in adults with idiopathic central diabetes insipidus.

PubMed

Hannon, M J; Orr, C; Moran, C; Behan, L A; Agha, A; Ball, S G; Thompson, C J

2012-05-01

Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, although many of these are thought to have an autoimmune basis. Published data have suggested that anterior hypopituitarism is common in childhood-onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus. We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone magnetic resonance imaging scanning and dynamic pituitary testing (either insulin tolerance testing or GHRH/arginine and short synacthen testing) to assess anterior pituitary function. One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. Thirty-three percent had at least one autoimmune disease in addition to central diabetes insipidus. Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not, therefore, be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology. © 2012 Blackwell Publishing Ltd.

[Gluten enteropathy].

PubMed

Macić-Dzanković, A; Sudí, J

1997-01-01

In this case report has been shown 32-old women patient. She was received on Department of Internal medicine of State Hospital "Sarajevo" because of prostration, weight loss (more than 20 kg) and frequently, abundant diarrheas. Clinical treatment, including biopsy of small intestine, referred on gluten-enteropathy. In war-stricken Sarajevo, when major part of food were bread, macaroni and pies, obviously there was perception of sensibility on gluten in this women who hadn't got any similar problem for her life. After adequate diet without gluten, on the control examination two month later, we can hardly recognize our patient. She can get more than 20 kg, without mental depression and would be married soon.

Newcomers in paediatric GI pathology: childhood enteropathies including very early onset monogenic IBD.

PubMed

Ensari, Arzu; Kelsen, Judith; Russo, Pierre

2018-01-01

Childhood enteropathies are a group of diseases causing severe chronic (>2-3 weeks) diarrhoea often starting in the first week of life with the potential for fatal complications for the affected infant. Early identification and accurate classification of childhood enteropathies are, therefore, crucial for making treatment decisions to prevent life-threatening complications. Childhood enteropathies are classified into four groups based on the underlying pathology: (i) conditions related to defective digestion, absorption and transport of nutrients and electrolytes; (ii) disorders related to enterocyte differentiation and polarization; (iii) defects of enteroendocrine cell differentiation; and (iv) disorders associated with defective modulation of intestinal immune response. While the intestinal mucosa is usually normal in enteropathies related to congenital transport or enzyme deficiencies, the intestinal biopsy in other disorders may reveal a wide range of abnormalities varying from normal villous architecture to villous atrophy and/or inflammation, or features specific to the underlying disorder including epithelial abnormalities, lipid vacuolization in the enterocytes, absence of plasma cells, lymphangiectasia, microorganisms, and mucosal eosinophilic or histiocytic infiltration. This review intends to provide an update on small intestinal biopsy findings in childhood enteropathies, the "newcomers", including very early onset monogenic inflammatory bowel disease (IBD), in particular, for the practicing pathologist.

Protein-losing enteropathy with intestinal lymphangiectasia in skeletal dysplasia with Lys650Met mutation.

PubMed

Yang, Chen; Dehner, Louis P

2016-11-01

Protein-losing enteropathy is a primary or secondary manifestation of a group of conditions, and etiologies which are broadly divisible into those with mucosal injury on the basis of inflammatory and ulcerative conditions, mucosal injury without erosions or ulcerations, and lymphatic abnormalities. We describe the first case of protein-losing enteropathy in a pediatric patient, with severe skeletal dysplasia consistent with thanatophoric dysplasia type I and DNA analysis that revealed a c.1949A>T (p.Lys650Met) in exon 15 of the FGFR3 gene. She presented with protein-losing enteropathy in her 6th month. Post-mortem examination revealed lymphangiectasia in the small intestine. To our knowledge, this is the first report of intestinal lymphangiectasia as a complication of skeletal dysplasia resulting in severe protein-losing enteropathy. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Protein-losing enteropathy with systemic lupus erythematosus effectively treated with octreotide and medium chain triglyceride diet: A case report].

PubMed

Kubo, Makoto; Uchida, Kousuke; Nakashima, Tadaaki; Oda, Seiko; Nakamura, Tomomi; Hashimoto, Shinichi; Watada, Toshiko; Nakamura, Hiroshi; Araki, Jun; Matsuzaki, Masunori; Yano, Masafumi

2015-01-01

In January 2009, a 62-year-old man presented with diarrhea, leg edema, and thrombopenia and was admitted to our hospital. The past medical history revealed Sjögren's syndrome and autoimmune hepatitis for which he had been administered prednisolone. On admission, a laboratory examination revealed massive hypoalbuminemia and high levels of C-reactive protein and platelet-associated IgG. Anti-double stranded DNA and anti-Sm antibodies were negative. Analysis of the bone marrow aspirate and Tc-99m albumin scintigraphy findings suggested autoimmune thrombocytopenic purpura (AITP) and protein-losing enteropathy (PLE), respectively. We diagnosed him as SLE, because past immunoserological testing had showed positivity for anti-double stranded DNA antibody and LE cells. Methylprednisolone pulse therapy and intravenous immunoglobulin therapy were ineffective. Rituximab was ineffective against PLE but was effective against AITP. Cyclosporine and Cyclophosphamide were ineffective against PLE. Subcutaneous injection of 200-μg octreotide daily and a medium chain triglyceride (MCT) diet was effective against PLE, and the patient's condition dramatically improved. The effectiveness of octreotide treatment and an MCT diet in the treatment of PLE with SLE is discussed.

Protein-losing enteropathy as initial manifestation of systemic lupus erythematosus.

PubMed

Carneiro, F O A A; Sampaio, L R; Brandão, L A R; Braga, L L B C; Rocha, F A C

2012-04-01

Protein-losing enteropathy is a rare manifestation of systemic lupus erythematosus. We report the case of an 18-year-old woman that presented initially with diarrhoea and anasarca. During evaluation, there was low serum albumin of 1.6 g/dl (3.5-5.2 g/dl) and a positive antinuclear antibody test (1:2560). Anti-Sm antibodies (ELISA) were positive in addition to low serum C3 of 35 mg/dl. A scintigraphy using 99mTc-labelled albumin was positive for abdominal protein loss. A diagnosis of systemic lupus erythematosus related protein-losing enteropathy was made. She was started on prednisolone 40 mg/day without amelioration; a month later, azathioprine (100 mg/day) was added, leading to normalization of serum albumin and resolution of symptoms within 4 months. After 1.5 years, the patient developed a 2.9 g 24-h proteinuria while still in remission of the protein-losing enteropathy, receiving 5 mg prednisone and 100 mg azathioprine daily.

Unsafe Child Feces Disposal is Associated with Environmental Enteropathy and Impaired Growth.

PubMed

George, Christine Marie; Oldja, Lauren; Biswas, Shwapon; Perin, Jamie; Sack, R Bradley; Ahmed, Shahnawaz; Shahnaij, Mohammad; Haque, Rashidul; Parvin, Tahmina; Azmi, Ishrat J; Bhuyian, Sazzadul Islam; Talukder, Kaisar A; Faruque, Abu G

2016-09-01

To investigate the relationship between unsafe child feces disposal, environmental enteropathy, and impaired growth, we conducted a prospective cohort study of 216 young children in rural Bangladesh. Using a prospective cohort study design in rural Bangladesh, unsafe child feces disposal, using the Joint Monitoring Program definition, was assessed using 5-hour structured observation by trained study personnel as well as caregiver reports. Anthropometric measurements were collected at baseline and at a 9-month follow-up. Stool was analyzed for fecal markers of environmental enteropathy: alpha-1-antitrypsin, myeloperoxidase, neopterin (combined to form an environmental enteropathy disease activity score), and calprotectin. Among 216 households with young children, 84% had an unsafe child feces disposal event during structured observation and 75% had caregiver reported events. There was no significant difference in observed unsafe child feces disposal events for households with or without an improved sanitation option (82% vs 85%, P = .72) or by child's age (P = .96). Children in households where caregivers reported unsafe child feces disposal had significantly higher environmental enteropathy scores (0.82-point difference, 95% CI 0.11-1.53), and significantly greater odds of being wasted (weight-for-height z score <-2 SDs) (9% vs 0%, P = .024). In addition, children in households with observed unsafe feces disposal had significantly reduced change in weight-for-age z-score (-0.34 [95% CI -0.68, -0.01] and weight-for-height z score (-0.52 [95% CI -0.98, -0.06]). Unsafe child feces disposal was significantly associated with environmental enteropathy and impaired growth in a pediatric population in rural Bangladesh. Interventions are needed to reduce this high-risk behavior to protect the health of susceptible pediatric populations. Copyright © 2016 Elsevier Inc. All rights reserved.

Is non‐steroidal anti‐inflammaory drug (NSAID) enteropathy clinically more important than NSAID gastropathy?

PubMed Central

Adebayo, D; Bjarnason, I

2006-01-01

The side effects of conventional non‐steroidal anti‐inflammatory drugs (NSAIDs) on the stomach is undoubtedly a serious public health problem contributing significantly to the morbidity and mortality of patients receiving these drugs. However, the damage of NSAIDs is not confined to the stomach. Indeed the short term and long term damage of NSAIDs on the small bowel (NSAID enteropathy) is more frequent than NSAID gastropathy. Furthermore, NSAID enteropathy is associated with complications (bleeding and protein loss). While many of these are mild, the serious events (significant bleeding, perforation, obstruction, and sudden death) are frequent as that reported for NSAID gastropathy. The diagnosis of NSAID enteropathy has been greatly aided by the introduction of wireless capsule enteroscopy. PMID:16517800

Is non-steroidal anti-inflammaory drug (NSAID) enteropathy clinically more important than NSAID gastropathy?

PubMed

Adebayo, D; Bjarnason, I

2006-03-01

The side effects of conventional non-steroidal anti-inflammatory drugs (NSAIDs) on the stomach is undoubtedly a serious public health problem contributing significantly to the morbidity and mortality of patients receiving these drugs. However, the damage of NSAIDs is not confined to the stomach. Indeed the short term and long term damage of NSAIDs on the small bowel (NSAID enteropathy) is more frequent than NSAID gastropathy. Furthermore, NSAID enteropathy is associated with complications (bleeding and protein loss). While many of these are mild, the serious events (significant bleeding, perforation, obstruction, and sudden death) are frequent as that reported for NSAID gastropathy. The diagnosis of NSAID enteropathy has been greatly aided by the introduction of wireless capsule enteroscopy.

Gastrointestinal haemorrhage due to lymphangiectasia caused by protein-losing enteropathy in the Fontan circulation.

PubMed

Gras, Pauline; Gottrand, Frédéric; Godart, François

2017-10-01

We report the case of a 14-year-old boy with severe protein-losing enteropathy after Fontan surgery that led to lymphangiectasia, which caused gastrointestinal haemorrhage and required invasive treatment to stop the bleeding. Through this case and a review of the literature on protein-losing enteropathy after Fontan surgery, we highlight a rare and serious presentation of the disease and the difficulties of diagnosis and management.

Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable Immune Deficiency.

PubMed

Sanchez, Lauren A; Maggadottir, Solrun Melkorka; Pantell, Matthew S; Lugar, Patricia; Rundles, Charlotte Cunningham; Sullivan, Kathleen E

2017-08-01

Common variable immunodeficiency (CVID) is a complex, heterogeneous immunodeficiency characterized by hypogammaglobulinemia, recurrent infections, and poor antibody response to vaccination. While antibiotics and immunoglobulin prophylaxis have significantly reduced infectious complications, non-infectious complications of autoimmunity, inflammatory lung disease, enteropathy, and malignancy remain of great concern. Previous studies have suggested that CVID patients diagnosed in childhood are more severely affected by these complications than adults diagnosed later in life. We sought to discern whether the rates of various infectious and non-infectious conditions differed between pediatric-diagnosed (ages 17 or younger) versus adult-diagnosed CVID (ages 18 or older). Using the United States Immunodeficiency Network (USIDNET) database, we performed a retrospective analysis of 457 children and adults with CVID, stratified by age at diagnosis. Chi-squared testing was used to compare pediatric versus adult groups. After correcting for multiple comparisons, we identified few statistically significant differences (p ≤ 0.0004) between pediatric and adult groups. Pediatric-onset CVID patients had more frequent diagnoses of otitis media, developmental delay, and failure to thrive compared with adult-onset CVID patients. Adult CVID patients were more frequently diagnosed with bronchitis, arthritis, depression, and fatigue. Diagnoses of autoimmunity, lymphoma, and other malignancies were higher in adults but not to a significant degree. Serum immunoglobulins (IgG, IgA, and IgM) and lymphocyte subsets did not differ significantly between the two groups. When complications of infections and co-morbid conditions were viewed categorically, there were few differences between pediatric-onset and adult-onset CVID patients. These results suggest that pediatric CVID is not a distinct phenotype. Major features were comparable across the groups. This study underscores the need for

NSAID gastropathy and enteropathy: distinct pathogenesis likely necessitates distinct prevention strategies

PubMed Central

Wallace, John L

2012-01-01

The mechanisms underlying the ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to cause ulceration in the stomach and proximal duodenum are well understood, and this injury can largely be prevented through suppression of gastric acid secretion (mainly with proton pump inhibitors). In contrast, the pathogenesis of small intestinal injury induced by NSAIDs is less well understood, involving more complex mechanisms than those in the stomach and proximal duodenum. There is clear evidence for important contributions to NSAID enteropathy of enteric bacteria, bile and enterohepatic recirculation of the NSAID. There is no evidence that suppression of gastric acid secretion will reduce the incidence or severity of NSAID enteropathy. Indeed, clinical data suggest little, if any, benefit. Animal studies suggest a significant exacerbation of NSAID enteropathy when proton pump inhibitors are co-administered with the NSAID. This worsening of damage appears to be linked to changes in the number and types of bacteria in the small intestine during proton pump inhibitor therapy. The distinct mechanisms of NSAID-induced injury in the stomach/proximal duodenum versus the more distal small intestine likely dictate distinct strategies for prevention. PMID:21627632

NSAID gastropathy and enteropathy: distinct pathogenesis likely necessitates distinct prevention strategies.

PubMed

Wallace, John L

2012-01-01

The mechanisms underlying the ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to cause ulceration in the stomach and proximal duodenum are well understood, and this injury can largely be prevented through suppression of gastric acid secretion (mainly with proton pump inhibitors). In contrast, the pathogenesis of small intestinal injury induced by NSAIDs is less well understood, involving more complex mechanisms than those in the stomach and proximal duodenum. There is clear evidence for important contributions to NSAID enteropathy of enteric bacteria, bile and enterohepatic recirculation of the NSAID. There is no evidence that suppression of gastric acid secretion will reduce the incidence or severity of NSAID enteropathy. Indeed, clinical data suggest little, if any, benefit. Animal studies suggest a significant exacerbation of NSAID enteropathy when proton pump inhibitors are co-administered with the NSAID. This worsening of damage appears to be linked to changes in the number and types of bacteria in the small intestine during proton pump inhibitor therapy. The distinct mechanisms of NSAID-induced injury in the stomach/proximal duodenum versus the more distal small intestine likely dictate distinct strategies for prevention. © 2011 The Author. British Journal of Pharmacology © 2011 The British Pharmacological Society.

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

Autoimmune bullous skin diseases. Part 1: Clinical manifestations.

PubMed

Kneisel, Andrea; Hertl, Michael

2011-10-01

Autoimmune bullous skin diseases are characterized by autoantibodies against adhesion molecules of the skin. Pemphigus is a disorder with an intraepidermal loss of adhesion and is characterized by fragile blisters and erosions. Pemphigus vulgaris often shows extensive lesions of the oral mucosa, while pemphigus foliaceus is commonly restricted to cutaneous involvement with puff pastry-like scale formation. Paraneoplastic pemphigus is obligatorily associated with malignancies and often presents as hemorrhagic stomatitis with multiforme-like exanthems. IgA pemphigus typically presents with pustules and annular plaques but not with mucosal involvement. The clinical spectrum of the pemphigoids includes tense blisters, urticarial plaques, and prurigo- like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a "cluster of jewels"-like pattern in childhood and is more heterogeneous in adulthood. Classical epidermolysis bullosa acquisita shows extensive skin fragility. Dermatitis herpetiformis is associated with gluten-sensitive enteropathy and manifests clinically with severe itching and papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The intention of the review is to demonstrate the heterogeneous clinical spectrum of autoimmune bullous disorders. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

Common autoimmune biomarkers, thyroid hormonal abnormalities, and beta cells dysfunction in patients with latent autoimmune diabetes in adults with type II diabetes mellitus.

PubMed

Yousefzadeh, Gholamreza; Gozashti, Mohammadhossein; Najafipour, Hamid; Gholamhosseinian, Najar Ahmad; Bahramnejad, Abbas; Shokouhi, Mostafa

2016-01-01

Latent autoimmune diabetes in adults (LADA) is autoimmune diabetes with a slow progression characterized by the presence of antibodies associated with Type I diabetes. The present study aimed to assess autoimmune characteristics in patients with LADA in Iran. We attempted to obtain a clear view of autoimmune conditions in LADA among our population. This study was sourced from the population-based survey of KERCARDS aiming assessment of cardiovascular risk factors among a great sample of Iranian population who were resident in Kerman, a great province in southern Iran. Among all diabetic patients who were negative for Anti Glutamic Acid Decarboxylase (GAD) antibody test, 120 were selected as the controls and among 80 patients who were positive for this test diagnosed as LADA, the recorded files of 57 patients were complete considered as the cases. The level of thyroxin is significantly lower in patients with LADA compared with the controls so 73.7% and 45% of patients had normal level of thyroxin, respectively. Also, those with LADA had considerably lower levels of both thyroid peroxydaseantibody (TPO-Ab) and C-peptide when compared with non-LADA group. Using multivariate analyses and with the presence of baseline variables including gender, age, and duration of disease, the diagnosis of LADA was associated with lower serum levels of Anti-TPO, C-peptide, and thyroxin, but not associated with the level of Anti-TTG in serum. LADA patients may face with lower serum levels of C-peptide and thyroid-specific antibodies indicating insulin therapy requirement and authoimmune fundaments of the disease, respectively. Copyright © 2016. Published by Elsevier Ltd.

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

USDA-ARS?s Scientific Manuscript database

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...

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. Copyright © 2016 by the American Academy of Pediatrics.

Household Environmental Conditions Are Associated with Enteropathy and Impaired Growth in Rural Bangladesh

PubMed Central

Lin, Audrie; Arnold, Benjamin F.; Afreen, Sadia; Goto, Rie; Huda, Tarique Mohammad Nurul; Haque, Rashidul; Raqib, Rubhana; Unicomb, Leanne; Ahmed, Tahmeed; Colford, John M.; Luby, Stephen P.

2013-01-01

We assessed the relationship of fecal environmental contamination and environmental enteropathy. We compared markers of environmental enteropathy, parasite burden, and growth in 119 Bangladeshi children (≤ 48 months of age) across rural Bangladesh living in different levels of household environmental cleanliness defined by objective indicators of water quality and sanitary and hand-washing infrastructure. Adjusted for potential confounding characteristics, children from clean households had 0.54 SDs (95% confidence interval [CI] = 0.06, 1.01) higher height-for-age z scores (HAZs), 0.32 SDs (95% CI = −0.72, 0.08) lower lactulose:mannitol (L:M) ratios in urine, and 0.24 SDs (95% CI = −0.63, 0.16) lower immunoglobulin G endotoxin core antibody (IgG EndoCAb) titers than children from contaminated households. After adjusting for age and sex, a 1-unit increase in the ln L:M was associated with a 0.33 SDs decrease in HAZ (95% CI = −0.62, −0.05). These results are consistent with the hypothesis that environmental contamination causes growth faltering mediated through environmental enteropathy. PMID:23629931

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

PubMed

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

2016-07-01

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. 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. 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. Co-administration of ciprofloxacin attenuated enterohepatic circulation of diclofenac and alleviated diclofenac-induced enteropathy in rats, partly via the inhibition of intestinal �

Autoimmune polyglandular syndromes: interplay between the immune and the endocrine systems leading to a diverse set of clinical diseases and new insights into immune regulation.

PubMed

Lebovitz, Harold E

2013-06-01

During the last 50 years, three major classes of autoimmune polyglandular syndromes (APSs) have been defined, and their characteristics and heritability have been delineated. Simultaneously, studies of the immunologic bases of these syndromes provided fundamental information in understanding immune regulation. Genetic analyses of patients and their families with APS type 1 (autoimmune polyendocrinopathy candidiasis, ectodermal dystrophy) identified the autoimmune regulator (AIRE) gene, which drives the expression of peripheral tissue-specific antigens in thymic cells and is critical in the development of self-tolerance. Mutations in this gene cause APS type 1. In contrast, studies in APS type 2 have been instrumental in understanding the role of human leukocyte antigen type II and related molecules in the pathogenesis of polygenetic autoimmune diseases such as type 1A diabetes. Immune dysfunction polyendocrinopathy, enteropathy, X-linked syndrome, which is caused by mutations in the forkhead box P3 gene, has been a model for studying regulatory T cell biology. The APSs epitomize the synergies that the merger of clinical and basic science can achieve. This is the environment that George Eisenbarth was able to create at the Barbara Davis Center for Diabetes.

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.

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

Autoimmune hepatitis in children: what is different from adult AIH?

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego

2009-08-01

Autoimmune hepatitis (AIH) is characterized by inflammatory liver histology, circulating non-organ-specific autoantibodies, and increased levels of immunoglobulin (Ig) G in the absence of a known etiology. Two types of childhood AIH are recognized according to seropositivity: smooth muscle antibody (SMA) and/or antinuclear antibody (ANA), which is AIH type 1; and antibodies to liver-kidney microsome type 1 (anti-LKM1), which is AIH type 2. There is a female predominance in both. Autoimmune hepatitis type 2 presents more acutely, at a younger age, and commonly with IgA deficiency; however, duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in the two groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to nonadherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long-term treatment is usually required, with only some 20% of AIH type 1 patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. The differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis, liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress. Copyright Thieme Medical Publishers.

Increased seroreactivity to proinsulin and homologous mycobacterial peptides in latent autoimmune diabetes in adults

PubMed Central

Niegowska, Magdalena; Delitala, Alessandro; Pes, Giovanni Mario; Delitala, Giuseppe

2017-01-01

Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressing form of immune-mediated diabetes that combines phenotypical features of type 2 diabetes (T2D) with the presence of islet cell antigens detected in type 1 diabetes (T1D). Heterogeneous clinical picture have led to the classification of patients based on the levels of antibodies against glutamic acid decarboxylase 65 (GADA) that correlate with clinical phenotypes closer to T1D or T2D when GADA titers are high or low, respectively. To date, LADA etiology remains elusive despite numerous studies investigating on genetic predisposition and environmental risk factors. To our knowledge, this is the first study aimed at evaluation of a putative role played by Mycobacterium avium subsp. paratuberculosis (MAP) as an infective agent in LADA pathogenesis. MAP is known to cause chronic enteritis in ruminants and has been associated with autoimmune disorders in humans. We analyzed seroreactivity of 223 Sardinian LADA subjects and 182 healthy volunteers against MAP-derived peptides and their human homologs of proinsulin and zinc transporter 8 protein. A significantly elevated positivity for MAP/proinsulin was detected among patients, with the highest prevalence in the 32-41-year-old T1D-like LADA subgroup, supporting our hypothesis of a possible MAP contribution in the development of autoimmunity. PMID:28472070

Autoimmunity-Associated PTPN22 Polymorphisms in Latent Autoimmune Diabetes of the Adult Differ from Those of Type 1 Diabetes Patients.

PubMed

Heneberg, Petr; Kocková, Lucie; Čecháková, Marie; Daňková, Pavlína; Černá, Marie

2018-06-12

A portion of adults with humoral immune changes have clinical diabetes that is initially not insulin-requiring (latent autoimmune diabetes of the adult, LADA). One of the genes strongly associated with autoimmune diabetes is PTPN22. We hypothesized that the manifestation and clinical features of LADA are linked to functional variants of PTPN22. We genotyped allelic frequencies of 1 protective and 3 risk-associated PTPN22 variants in 156 Czech LADA patients, 194 type 2 diabetes mellitus patients with LADA-like progression to insulinotherapy and 324 type 1 diabetes mellitus patients, and subsequently examined the associations of PTPN22 variants with the expression of autoantibodies and other clinical features of LADA. We challenged the paradigm that stated that the PTPN22 c.1858T allele serves as a risk allele for LADA, although we confirmed its risk status in the geographically matched T1DM cohort. In contrast, the frequencies of other PTPN22 alleles (c.-1123C, c.788A and c.1970-852C) differed significantly from the healthy controls. We confirmed gender-related differences in the frequency of some PTPN22 polymorphisms (but not c.1858C>T) in LADA. The particular PTPN22 alleles and genotypes were associated with specific clinical features of the examined patients (autoantibodies, HbA1c and age at diagnosis of diabetes). The variability in PTPN22 haplotypes suggests that the genetic signature of LADA is independent and should not be considered a hybrid form of T1DM and T2DM. Further studies should elucidate the associations with clinical characteristics of the LADA patients and focus on the newly emerging types of diabetes with the disease onset in early to mid-adulthood. © 2018 S. Karger AG, Basel.

Enteropathy-associated T-cell lymphoma--a clinicopathologic and array comparative genomic hybridization study.

PubMed

Ko, Young Hyeh; Karnan, Sivasundaram; Kim, Kyeong Mee; Park, Cheol Keun; Kang, Eun Suk; Kim, Young Ho; Kang, Won Ki; Kim, Seok Jin; Kim, Won Seog; Lee, Woo Yong; Chun, Ho Kyung; Seto, Masao

2010-09-01

According to the new World Health Organization classification system, there are 2 types of enteropathy-associated T-cell lymphoma. Type 1 is associated with celiac disease and accounts for the majority of cases in Western countries, whereas type 2 is not associated with celiac disease. To characterize enteropathy-associated T-cell lymphoma types in Korea, we carried out clinicopathologic and immunophenotypic analyses of 8 Koreans with enteropathy-associated T-cell lymphoma and investigated genomic profile using array comparative genomic hybridization. The tumors involved the small intestine in 5 patients and the colorectum in 3 patients. Two patients carried an HLA DQB10302 allele that corresponds to HLA DQ8. None of the patients had gluten-sensitive malabsorption syndrome. Intraepithelial lymphocytosis was observed in all patients. The sizes of the tumor cells were small or small-to-medium in 7 cases and medium-to-large in 1 case. The immunophenotypes of the tumor cells were CD4-CD8+CD56+ in 4 cases, CD4-CD8+CD56- in 1 case, CD4-CD8-CD56+ in 2 cases, and CD4-CD8-CD56- in 1 case. Array comparative genomic hybridization analysis showed that chromosome 9q33-q34.1 gain was present in 4 (80%) of the 5 cases examined. Other recurrent genomic alterations were gain of 6p21.1-21.31 (3/5, 60%), gain of 19q (2/5), and the loss of 3p12.1-p12.2 (2/5) and 3q26.31 (2/5). These results suggest that the most prevalent type of enteropathy-associated T-cell lymphoma in this geographic region is type 2, and the genetic changes associated with it are similar to those in Western countries. Copyright 2010 Elsevier Inc. All rights reserved.

Survival of adults with systemic autoimmune rheumatic diseases and pulmonary arterial hypertension after lung transplantation.

PubMed

Bernstein, Elana J; Bathon, Joan M; Lederer, David J

2018-05-01

Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality in adults with systemic autoimmune rheumatic diseases (ARDs). The aim of this study was to determine whether adults with ARDs and PAH on right-sided heart catheterization (ARD-PAH) have increased mortality following lung transplantation compared with those with PAH not due to an ARD. We conducted a retrospective cohort study of 93 adults with ARD-PAH and 222 adults with PAH who underwent lung transplantation in the USA between 4 May 2005 and 9 March 2015 using data from the United Network for Organ Sharing. We examined associations between diagnosis and survival after lung transplantation using stratified Cox models adjusted for potential confounding recipient factors. Among adults undergoing lung transplantation in the USA, we did not detect a difference in the multivariable-adjusted mortality rate between those with ARD-PAH and those with PAH [hazard ratio 0.75 (95% CI 0.47, 1.19)]. The presence of an ARD was not associated with increased mortality after lung transplantation in adults with PAH.

Easily obtainable clinical features increase the diagnostic accuracy for latent autoimmune diabetes in adults: an evidence-based report.

PubMed

Lutgens, Maurice W M D; Meijer, Melanie; Peeters, Babette; Poulsen, Marie-Louise N F; Rutten, Marjet J; Bots, Michiel L; van der Heijden, Geert J M G; Soedamah-Muthu, Sabita S

2008-12-01

Latent autoimmune diabetes in adults (LADA) represents a subgroup of diabetes mellitus. LADA is characterised by adult-onset diabetes and circulating autoimmune antibodies. LADA patients may need a different therapeutic approach than the usual type 2 diabetes mellitus. When LADA is inadequately diagnosed as type 2 diabetes mellitus, LADA patients will mistakenly be exposed to a high dose of oral glucose lowering drugs and their possible side effects. To assess which clinical features predict the presence or absence of LADA in patients older than 25 years presenting with hyperglycemia. A structured Medline and Embase search was conducted. Titles and abstracts were screened using predetermined selection criteria. Critical appraisal was based on standardized validity criteria for diagnostic research. One-hundred and eighty-four papers were retrieved of which after assessment of relevance and validity 2 studies remained for further analysis. One study reported a probability of LADA of 0.99 with one or two out of the following five clinical features: age at onset <50 years; acute symptoms; BMI<25 kg/m(2); a history of autoimmune disease; a family history positive for diabetes mellitus. The other study reported a probability of LADA of zero with none of the following clinical features and of 0.32 with one out of three: fasting blood glucose> or =15 mmol/l and/or HbA(1c)> or =10%; 10% reduction in body weight in the previous 3 months; BMI<25 kg/m(2). Further testing for LADA by measurement of autoimmune antibodies appears to be unnecessary in the absence of a specific set of clinical features. Before initiating therapy applying the above criteria may help to separate LADA from usual type 2 diabetes.

Behçet disease and protein-losing enteropathy due to intestinal lymphangiectasia.

PubMed

Rodríguez-Muguruza, Samantha; Caballero, Noemí; Horneros, Judith; Domenech, Eugeni; Mateo, Lourdes

2015-01-01

We report an unusual case of a patient with Behçet's disease that developed protein-losing enteropathy due to intestinal lymphangiectasia. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Two-dimensional grayscale ultrasound and spectral Doppler waveform evaluation of dogs with chronic enteropathies.

PubMed

Gaschen, Lorrie; Kircher, Patrick

2007-08-01

Sonography is an important diagnostic tool to examine the gastrointestinal tract of dogs with chronic diarrhea. Two-dimensional grayscale ultrasound parameters to assess for various enteropathies primarily focus on wall thickness and layering. Mild, generalized thickening of the intestinal wall with maintenance of the wall layering is common in inflammatory bowel disease. Quantitative and semi-quantitative spectral Doppler arterial waveform analysis can be utilized for various enteropathies, including inflammatory bowel disease and food allergies. Dogs with inflammatory bowel disease have inadequate hemodynamic responses during digestion of food. Dogs with food allergies have prolonged vasodilation and lower resistive and pulsatility indices after eating allergen-inducing foods.

Autoimmune diseases in asthma.

PubMed

Tirosh, Amir; Mandel, Dror; Mimouni, Francis B; Zimlichman, Eyal; Shochat, Tzippora; Kochba, Ilan

2006-06-20

Previous research has suggested an inverse relationship between T-helper 2-related atopic disorders, such as asthma, and T-helper 1-related autoimmune diseases. One controversial hypothesis postulates that asthma provides a protective effect for the development of autoimmune-related disorders. To assess the rate of newly diagnosed autoimmune disorders in a large cohort of young adults. Using cross-sectional data from the Israeli Defense Force database, the authors analyzed the prevalence of autoimmune disorders in asthmatic and nonasthmatic military personnel between 1980 and 2003. A follow-up study traced newly diagnosed autoimmune disorders among asthmatic and nonasthmatic individuals from the time of enrollment in military service until discharge (22 and 36 months for women and men, respectively). General community. 307,367 male and 181,474 female soldiers in compulsory military service who were between 18 and 21 years of age. Cases of type 1 diabetes mellitus, vasculitis, immune thrombocytopenic purpura, inflammatory bowel disease, rheumatoid arthritis, and the antiphospholipid syndrome. Of 488,841 participants at enrollment, significantly more women than men had autoimmune disorders. Compared with asthmatic women, nonasthmatic women had a significantly higher prevalence of all autoimmune disorders except for the antiphospholipid syndrome. Type 1 diabetes mellitus, vasculitis, and rheumatoid arthritis were less prevalent in men with asthma than in those without. During the follow-up period, vasculitis and rheumatoid arthritis were more frequently diagnosed in nonasthmatic persons of both sexes. There was a significantly higher incidence of immune thrombocytopenic purpura, inflammatory bowel disease, and the antiphospholipid syndrome in nonasthmatic women and a statistically significantly higher incidence of type 1 diabetes mellitus in nonasthmatic men. The study was limited to a population of young military recruits; therefore, its findings are not necessarily

Warfarin hypersensitivity due to gluten-sensitive enteropathy: a case study.

PubMed

Kwolek, Sara; Deming, Paula

2012-01-01

A 53 year old female who was maintained on long-term warfarin therapy due to history of pulmonary embolism, repeatedly presents with an abnormally prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). After many asymptomatic episodes were corrected with Vitamin K therapy to temporarily reverse the effects of the warfarin, the cause of the apparent coagulopathy was further investigated. Factor Activity Assays of the common pathway factors II, IX, and X all revealed critically low values; below the threshold even a loading dose of warfarin is typically capable of eliciting. The patient tested strongly positive for Tissue Transglutaminase IgA, which is highly suggestive of a gluten-sensitive enteropathy. One effect of this condition is malabsorption due to flattened intestinal villi. The patient was determined to have an acquired vitamin K deficiency secondary to gluten-sensitive enteropathy. Her condition was exacerbated by the long-term warfarin therapy, resulting in the prolonged PT and PTT. The patient was treated with vitamin K therapy, which reversed the deficiency and corrected her abnormal coagulation results.

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

USDA-ARS?s Scientific Manuscript database

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...

Antibody-Mediated Autoimmune Encephalitis in Childhood.

PubMed

Brenton, J Nicholas; Goodkin, Howard P

2016-07-01

The differential diagnosis of encephalitis in childhood is vast, and evaluation for an etiology is often unrevealing. Encephalitis by way of autoimmunity has long been suspected, as in cases of acute disseminated encephalomyelitis; however, researchers have only recently reported evidence of antibody-mediated immune dysregulation resulting in clinical encephalitis. These pathologic autoantibodies, aimed at specific neuronal targets, can result in a broad spectrum of symptoms including psychosis, catatonia, behavioral changes, memory loss, autonomic dysregulation, seizures, and abnormal movements. Autoimmune encephalitis in childhood is often quite different from adult-onset autoimmune encephalitis in clinical presentation, frequency of tumor association, and ultimate prognosis. As many of the autoimmune encephalitides are sensitive to immunotherapy, prompt diagnosis and initiation of appropriate treatment are paramount. Here we review the currently recognized antibody-mediated encephalitides of childhood and will provide a framework for diagnosis and treatment considerations. Copyright © 2016 Elsevier Inc. All rights reserved.

Direct Biomarkers of Microbial Translocation Correlate with Immune Activation in Adult Zambians with Environmental Enteropathy and Hepatosplenic Schistosomiasis

PubMed Central

Kaonga, Patrick; Kaimoyo, Evans; Besa, Ellen; Zyambo, Kanekwa; Sinkala, Edford; Kelly, Paul

2017-01-01

Abstract. Microbial translocation is a poorly understood consequence of several disorders such as environmental enteropathy (EE) and hepatosplenic schistosomiasis (HSS). Herein, we compared biomarkers of microbial origin and immune activation in adults with these disorders and in healthy controls. A cross-sectional study was conducted in participants with EE recruited from Misisi compound, Lusaka, Zambia; HSS patients and healthy controls from the University Teaching Hospital, Lusaka. Plasma lipopolysaccharides (LPSs) was measured by limulus amoebocyte lysate assay, plasma 16S ribosomal RNA (16S rRNA) gene copy number was quantified by quantitative real-time polymerase chain reaction, Toll-like receptor ligand (TLRL) activity by QUANTI-Blue detection medium, and cytokines from cell culture supernatant by Cytometric Bead Array. In univariate analysis LPS, 16S rRNA gene copy number, and TLR activity were all high and correlated with each other and with cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10, and IL-4 secreted by the RAW-Blue cells. After controlling for baseline characteristic, biomarkers of microbial translocation in blood were predictors of TNF-α, IL-6, and IL-10 activation in cell culture supernatant from EE participants and HSS patients but not in healthy controls. TLR activity showed the strongest correlation with TNF-α. These data provide correlative evidence that microbial translocation contributes to systemic cytokine activation in two disorders common in the tropics, with total TLR ligand estimation showing the strongest correlation with TNF-α (r = 0.66, P < 0.001). PMID:29140241

FFA3 Activation Stimulates Duodenal Bicarbonate Secretion and Prevents NSAID-Induced Enteropathy via the GLP-2 Pathway in Rats.

PubMed

Said, Hyder; Akiba, Yasutada; Narimatsu, Kazuyuki; Maruta, Koji; Kuri, Ayaka; Iwamoto, Ken-Ichi; Kuwahara, Atsukazu; Kaunitz, Jonathan D

2017-08-01

Therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enteropathy in humans and experimental animals, a cause of considerable morbidity. Unlike foregut NSAID-associated mucosal lesions, most treatments for this condition are of little efficacy. We propose that the endogenously released intestinotrophic hormone glucagon-like peptide-2 (GLP-2) prevents the development of NSAID-induced enteropathy. Since the short-chain fatty acid receptor FFA3 is expressed on enteroendocrine L cells and on enteric nerves in the gastrointestinal tract, we further hypothesized that activation of FFA3 on L cells protects the mucosa from injury via GLP-2 release with enhanced duodenal HCO 3 - secretion. We thus investigated the effects of synthetic selective FFA3 agonists with consequent GLP-2 release on NSAID-induced enteropathy. We measured duodenal HCO 3 - secretion in isoflurane-anesthetized rats in a duodenal loop perfused with the selective FFA3 agonists MQC or AR420626 (AR) while measuring released GLP-2 in the portal vein (PV). Intestinal injury was produced by indomethacin (IND, 10 mg/kg, sc) with or without MQC (1-10 mg/kg, ig) or AR (0.01-0.1 mg/kg, ig or ip) treatment. Luminal perfusion with MQC or AR (0.1-10 µM) dose-dependently augmented duodenal HCO 3 - secretion accompanied by increased GLP-2 concentrations in the PV. The effect of FFA3 agonists was inhibited by co-perfusion of the selective FFA3 antagonist CF3-MQC (30 µM). AR-induced augmented HCO 3 - secretion was reduced by iv injection of the GLP-2 receptor antagonist GLP-2(3-33) (3 nmol/kg), or by pretreatment with the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTR inh -172 (1 mg/kg, ip). IND-induced small intestinal ulcers were dose-dependently inhibited by intragastric administration of MQC or AR. GLP-2(3-33) (1 mg/kg, ip) or CF3-MQC (1 mg/kg, ig) reversed AR-associated reduction in IND-induced enteropathy. In contrast, ip injection of AR had no effect

[Coexistence of autoimmune polyglandular syndrome type 3 with diabetes insipidus].

PubMed

Krysiak, Robert; Okopień, Bogusław

2015-01-01

Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract

Detecting protein losing enteropathy by Tc-99m dextran scintigraphy: a novel experience.

PubMed

Kapoor, Seema; Ratan, Simmi K; Kashyap, Ravi; Mittal, S K; Rajeshwari, K; Rawat, H; Verma, Jyoti

2002-09-01

To evaluate protien using enteropathy by Tc-99m dextran scintigraphy. Methods for detecting protein loss from the intestine revolve around fecal nitrogen excretion, the clearance of alpha-1 antitrypsin in stools and by endoscopic biopsy. The diagnosis of protein-losing enteropathy (PLE) can also be established by a scintigraphic method that is noninvasive, simple and requires no patient preparation or motivation. This diagnostic modality can also delineate the site of protein loss, thereby offering a targeted approach, and if need be, surgery. Radiolabelling of a non-protein, noncolloidal, nonparticulate and biofriendly molecule like dextran with Technetium-99m for imaging enteric protein loss was utilized in imaging eight children with PLE. The results were encouraging. The authors advocate the use of this diagnostic tool in identifying patients with PLE, particularly in the pediatric age group.

Effect of Saccharomyces boulardii in dog with chronic enteropathies: double-blinded, placebo-controlled study.

PubMed

D'Angelo, Simona; Fracassi, Federico; Bresciani, Francesca; Galuppi, Roberta; Diana, Alessia; Linta, Nikolina; Bettini, Giuliano; Morini, Maria; Pietra, Marco

2018-03-03

Saccharomyces boulardii is used to treat acute and chronic enteropathies in humans, but to date, no studies have evaluated the use of this yeast in dogs. The current study, a prospective non-randomised, double-blinded, placebo-controlled study, evaluated the effects of S boulardii in healthy dogs and dogs with chronic enteropathies (CE). Four healthy dogs and 20 dogs with CE were included. In healthy dogs, S boulardii was administered for 10 days. Possible short-term adverse effects were recorded, and quantitative stool cultures for yeasts were performed. In dogs with CE, S boulardii or a placebo was administered in addition to standard treatment protocols. Canine Chronic Enteropathy Clinical Activity Index, abdominal ultrasonography, gastroenteroscopy and histology were performed at the time of diagnosis and after 60 days of treatment. In healthy dogs, S boulardii reached a steady state in five days and was completely eliminated on day 4 after administration. No short-term side effects were seen. Clinical activity index, stool frequency, stool consistency and body condition score improved significantly in dogs with CE receiving S boulardii versus the placebo. In conclusion, S boulardii can be safely used in dogs with CE and seems to achieve better control of clinical signs than standard therapy alone. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

Self-limited coeliac-like enteropathy: a series of 18 cases highlighting another coeliac disease mimic.

PubMed

Brown, Ian S; Bettington, Andrew; Bettington, Mark; Rosty, Christophe

2016-01-01

To describe the clinical and pathological features of a series of patients with biopsy findings of a coeliac disease-like enteropathy in the setting of an acute illness. Eighteen cases of an abrupt-onset, self-limited illness with coeliac-like enteropathy (SLCE) were collected prospectively. Medication reaction, immune disorder, food allergy and parasitic infection were excluded. Coeliac disease was excluded by the transient nature of the illness and absence of tissue transglutaminase (TTG) elevation (nine of nine) or human leucocyte antigen (HLA)-DQ2/DQ8 haplotype (eight of nine). Clinical symptoms were recorded and histopathological findings in all gastrointestinal sites were quantified. Findings in the duodenum were compared to a coeliac disease control group. In 12 cases the clinical diagnosis was infective enteritis, probably viral in type. In six cases, a definite diagnosis was not established. Histological differences from coeliac disease included intra-epithelial neutrophil infiltration (P < 0.001), fewer intra-epithelial lymphocytes (P = 0.038) and uniform or crypt predominant intra-epithelial lymphocytosis in SCLE. One case displayed pan-gastrointestinal tract lymphocytosis. All resolved within 6 months. Histopathologists need to be aware that a coeliac disease-like enteropathy may occur in the setting of an acute gastrointestinal illness and resolve without sequelae. © 2015 John Wiley & Sons Ltd.

Epstein-Barr virus-associated enteropathy as a complication of infectious mononucleosis mimicking peripheral T-cell lymphoma.

PubMed

Tamura, Shinobu; Maruyama, Dai; Miyagi Maeshima, Akiko; Taniguchi, Hirokazu; Kakugawa, Yasuo; Mori, Masakazu; Azuma, Teruhisa; Kim, Sung-Won; Watanabe, Takashi; Kobayashi, Yukio; Tobinai, Kensei

2013-01-01

A 32-year-old man presented with a fever. A laboratory examination detected atypical lymphocytes and liver enzyme elevation. The serological tests for Epstein-Barr virus (EBV) were consistent with an acute infection pattern. Computed tomograpy showed bowel wall thickening, and colonoscopy revealed numerous ulcerations. The histological findings from the biopsy specimens from the colon were consistent with peripheral T-cell lymphoma (PTCL), and in situ hybridization detected EBER-1 in the atypical lymphocytes. Because his clinical and endoscopic abnormalities improved without medication, we diagnosed the patient with EBV-associated enteropathy. We herein report a rare case of EBV-associated enteropathy that required careful differentiation from PTCL.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy

PubMed Central

Whitfield-Cargile, Canaan M.; Cohen, Noah D.; Chapkin, Robert S.; Weeks, Brad R.; Davidson, Laurie A.; Goldsby, Jennifer S.; Hunt, Carrie L.; Steinmeyer, Shelby H.; Menon, Rani; Suchodolski, Jan S.; Jayaraman, Arul; Alaniz, Robert C.

2016-01-01

ABSTRACT Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used classes of medications in the world. Unfortunately, NSAIDs induce an enteropathy associated with high morbidity and mortality. Although the pathophysiology of this condition involves the interaction of the gut epithelium, microbiota, and NSAIDs, the precise mechanisms by which microbiota influence NSAID enteropathy are unclear. One possible mechanism is that the microbiota may attenuate the severity of disease by specific metabolite-mediated regulation of host inflammation and injury. The microbiota-derived tryptophan-metabolite indole is abundant in the healthy mammalian gut and positively influences intestinal health. We thus examined the effects of indole administration on NSAID enteropathy. Mice (n = 5 per group) were treated once daily for 7 days with an NSAID (indomethacin; 5 mg/kg), indole (20 mg/kg), indomethacin plus indole, or vehicle only (control). Outcomes compared among groups included: microscopic pathology; fecal calprotectin concentration; proportion of neutrophils in the spleen and mesenteric lymph nodes; fecal microbiota composition and diversity; small intestinal mucosal transcriptome; and, fecal tryptophan metabolites. Co-administration of indole with indomethacin: significantly reduced mucosal pathology scores, fecal calprotectin concentrations, and neutrophilic infiltration of the spleen and mesenteric lymph nodes induced by indomethacin; modulated NSAID-induced perturbation of the microbiota, fecal metabolites, and inferred metagenome; and, abrogated a pro-inflammatory gene expression profile in the small intestinal mucosa induced by indomethacin. The microbiota-derived metabolite indole attenuated multiple deleterious effects of NSAID enteropathy, including modulating inflammation mediated by innate immune responses and altering indomethacin-induced shift of the microbiota. PMID:27007819

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

USDA-ARS?s Scientific Manuscript database

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...

[Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

PubMed

Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana

2011-01-01

Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

Mouthing of Soil Contaminated Objects is Associated with Environmental Enteropathy in Young Children.

PubMed

Morita, Tomohiko; Perin, Jamie; Oldja, Lauren; Biswas, Shwapon; Sack, R Bradley; Ahmed, Shahnawaz; Haque, Rashidul; Bhuiyan, Nurul Amin; Parvin, Tahmina; Bhuyian, Sazzadul Islam; Akter, Mahmuda; Talukder, Kaisar A; Shahnaij, Mohammad; Faruque, Abu G; George, Christine Marie

2017-06-01

To characterise childhood mouthing behaviours and to investigate the association between object-to-mouth and food-to-mouth contacts, diarrhoea prevalence and environmental enteropathy. A prospective cohort study was conducted of 216 children ≤30 months of age in rural Bangladesh. Mouthing contacts with soil and food and objects with visible soil were assessed by 5-h structured observation. Stool was analysed for four faecal markers of intestinal inflammation: alpha-1-antitrypsin, myeloperoxidase, neopterin and calprotectin. Overall 82% of children were observed mouthing soil, objects with visible soil, or food with visible soil during the structured observation period. Sixty two percent of children were observed mouthing objects with visible soil, 63% were observed mouthing food with visible soil, and 18% were observed mouthing soil only. Children observed mouthing objects with visible soil had significantly elevated faecal calprotectin concentrations (206.81 μg/g, 95% confidence interval [CI]: 6.27, 407.36). There was also a marginally significant association between Escherichia coli counts in soil from a child's play space and the prevalence rate of diarrhoea (diarrhoea prevalence ratio: 2.03, 95% CI 0.97, 4.25). These findings provide further evidence to support the hypothesis that childhood mouthing behaviour in environments with faecal contamination can lead to environmental enteropathy in susceptible paediatric populations. Furthermore, these findings suggest that young children mouthing objects with soil, which occurred more frequently than soil directly (60% vs. 18%), was an important exposure route to faecal pathogens and a risk factor for environmental enteropathy. © 2017 John Wiley & Sons Ltd.

[SPECIFIC CLINICAL FEATURES OF TYPE 1 AUTOIMMUNE POLYGLANDULAR SYNDROME].

PubMed

Mikhina, M S; Molashenko, N V; Troshina, E A; Orlova, E M; Sozaeva, L S; Eystein, S H; Breivik, S

2015-01-01

Autoimmune polyglandular syndrome is a primary autoimmune disorder affecting two or more peripheral endocrine glands and responsible for their incompetence. It is frequently combined with various organ-specific non-endocrine diseases. Patients with this pathology need life-long replacement therapy and dynamic observation by endocrinologists and other specialists to monitor the effectiveness of the treatment and detect new components of the disease. We report a variant of type 1 autoimmune polyglandular syndrome. Special emphasis is laid on the importance of succession of actions of endocrinologists and specialists in related medical disciplines dealing with children and adult patients.

Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology.

PubMed Central

Batman, P A; Miller, A R; Forster, S M; Harris, J R; Pinching, A J; Griffin, G E

1989-01-01

Jejunal biopsy specimens from 20 human immunodeficiency virus (HIV) positive male homosexual patients were analysed and compared with those of a control group to determine whether the abnormalities were caused by the virus or by opportunistic infection. The degree of villous atrophy was estimated with a Weibel eyepiece graticule, and this correlated strongly with the degree of crypt hyperplasia, which was assessed by deriving the mean number of enterocytes in the crypts. The density of villous intraepithelial lymphocytes fell largely within the normal range, either when expressed in relation to the number of villous enterocytes or in relation to the length of muscularis mucosae. Villous enterocytes showed mild non-specific abnormalities. Pathogens were sought in biopsy sections and in faeces. Crypt hyperplastic villous atrophy occurred at all clinical stages of HIV disease and in the absence of detectable enteropathogens. An analogy was drawn between HIV enteropathy and the small bowel changes seen in experimental graft-versus-host disease. It is suggested that the pathogenesis of villous atrophy is similar in the two states, the damage to the jejunal mucosa in HIV enteropathy being inflicted by an immune reaction mounted in the lamina propria against cells infected with HIV. Images Fig 1 Fig 2 PMID:2703544

Sensitization to Gliadin Induces Moderate Enteropathy and Insulitis in Nonobese Diabetic-DQ8 Mice

PubMed Central

Galipeau, Heather J.; Rulli, Nestor E.; Jury, Jennifer; Huang, Xianxi; Araya, Romina; Murray, Joseph A.; David, Chella S.; Chirdo, Fernando G.; McCoy, Kathy D.; Verdu, Elena F.

2012-01-01

Celiac disease (CD) is frequently diagnosed in patients with type 1 diabetes (T1D), and T1D patients can exhibit Abs against tissue transglutaminase, the auto-antigen in CD. Thus, gliadin, the trigger in CD, has been suggested to have a role in T1D pathogenesis. The objective of this study was to investigate whether gliadin contributes to enteropathy and insulitis in NOD-DQ8 mice, an animal model that does not spontaneously develop T1D. Gliadin-sensitized NOD-DQ8 mice developed moderate enteropathy, intraepithelial lymphocytosis, and barrier dysfunction, but not insulitis. Administration of anti-CD25 mAbs before gliadin-sensitization induced partial depletion of CD25+Foxp3+ T cells and led to severe insulitis, but did not exacerbate mucosal dysfunction. CD4+ T cells isolated from pancreatic lymph nodes of mice that developed insulitis showed increased proliferation and proinflammatory cytokines after incubation with gliadin but not with BSA. CD4+ T cells isolated from nonsensitized controls did not response to gliadin or BSA. In conclusion, gliadin sensitization induced moderate enteropathy in NOD-DQ8 mice. However, insulitis development required gliadin-sensitization and partial systemic depletion of CD25+Foxp3+ T cells. This humanized murine model provides a mechanistic link to explain how the mucosal intolerance to a dietary protein can lead to insulitis in the presence of partial regulatory T cell deficiency. PMID:21911598

Autoimmunity and autoimmune co-morbidities in psoriasis.

PubMed

Furue, Kazuhisa; Ito, Takamichi; Tsuji, Gaku; Kadono, Takafumi; Nakahara, Takeshi; Furue, Masutaka

2018-05-01

Psoriasis is characterized by widespread scaly erythematous plaques that cause significant physical and psychological burdens for the affected individuals. Accelerated inflammation driven by the tumour necrosis factor-α/interleukin-23/interleukin-17 axis is now known to be the major mechanism in the development of psoriasis. In addition, psoriasis has an autoimmune nature that manifests as autoreactive T cells and is co-morbid with other autoimmune diseases, such as autoimmune bullous diseases, vitiligo, alopecia and thyroiditis. In this article, we review the recent topics on autoimmunity and autoimmune co-morbidities in psoriasis. © 2018 John Wiley & Sons Ltd.

Protein-losing enteropathy as a rare complication of the ketogenic diet.

PubMed

Moriyama, Kengo; Watanabe, Mio; Yamada, Yoshiyuki; Shiihara, Takashi

2015-05-01

The ketogenic diet is a valuable therapy for patients with intractable epilepsy, but it can result in a variety of complications that sometimes limits its usefulness. Hypoproteinemia is one of the common adverse effects of this diet, although the underling mechanism is largely unknown except for the diet's reduced protein intake. Only one case of protein-losing enteropathy during the ketogenic diet has been reported. A previously healthy 9-year-old girl experienced fever for 5 days then suddenly developed convulsive seizures that subsequently evolved to severe refractory status epilepticus. After multiple antiepileptic drugs failed to improve the patient's condition, we introduced the ketogenic diet. Although her seizures diminished, her course was complicated by hypoproteinemia. An abdominal dynamic scintigraphy and colonoscopy findings indicated protein-losing enteropathy with nonspecific mucosal inflammation. Her nutritional status deteriorated; thus, we discontinued the ketogenic diet. Her nutritional status gradually improved, whereas her seizures increased. Hypoproteinemia during the ketogenic diet is common, but the underlying etiologies are not well understood. Abdominal dynamic scintigraphy could be valuable for clarifying the etiology of hypoproteinemia during the ketogenic diet. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Kocuria kristinae-caused sepsis in an infant with congenital tufting enteropathy.

PubMed

Aydin, Malik; Ganschow, Rainer; Jankofsky, Martin

2017-01-01

Aydin M, Ganschow R, Jankofsky M. Kocuria kristinae-caused sepsis in an infant with congenital tufting enteropathy. Turk J Pediatr 2017; 59: 93-96. Congenital tufting enteropathy (CTE) is characterized by the early-onset of chronic diarrhea and the inability to develop. It is a rare congenital disease with a low prevalence of 1:50,000 - 100,000 live births p.a. The histopathology is characterized by villous atrophy and the characteristic epithelial tufts. Recent identification of causative mutations in EpCAM has enhanced our understanding of this disease. Due to its severe clinical course, patients are dependent on parenteral nutrition to thrive successfully. Catheter-associated blood stream infections have become the primary problem for pediatric patients. Infections with Kocuria kristinae are rare. This report is about a 3-month-old girl with CTE suffering from a central venous catheter related mono-sepsis by K. kristinae. A sepsis therapy with meropenem and vancomycin improved her general state rapidly. Only few cases in the literature with CTE and K. kristinae are described. To the best of our knowledge, this is the first report presenting two coincidences in one case.

Cannabidiol limits Tcell-mediated chronic autoimmune myocarditis: implications to autoimmune disorders and organ transplantation.

PubMed

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

2016-01-08

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 non-psychoactive constituent of Marijuana which exerts antiinflammatory effects independent from classical cannabinoid receptors. Recently 80 clinical trials have been reported investigating 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 FDA 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, fibrosis (measured by qRT-PCR, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.

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

[Cow's milk protein sensitive enteropathy].

PubMed

Harms, H K

1982-01-01

Cow's milk protein sensitive enteropathy (CMPSE) is characterized by the following items: 1. The great majority of affected infants have not been breast fed or only for a few days. Additional risks are immaturity, preceding enteritis, trisomy 21, and abdominal operation in the newborn. 2. Half of the patients become ill during the first two weeks after starting cow's milk formula. The main symptoms are watery, mucus containing diarrhea, vomiting, abdominal distension, pallor and rapid weight loss. 3. In CMPSE the small intestinal mucosa shows varying degrees of inflammation and villous atrophy. Bloody stools refer to large bowel affection. 4. CMPSE is always transitory and usually persists for less than one year. Inadequate treatment leads to "severe protracted diarrhea" or "intractable diarrhea" syndrome. Soya-based formula should not be the diet of first choice, since secondary intolerance to soya proteins will frequently develop. Exclusive breast feeding during the first months of life is the best prophylaxis of CMPSE.

Association between demyelinating disease and autoimmune rheumatic disease in a pediatric population.

PubMed

Amorim, Ana Luiza M; Cabral, Nadia C; Osaku, Fabiane M; Len, Claudio A; Oliveira, Enedina M L; Terreri, Maria Teresa

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and in their families has been broadly investigated and discussed. Recent studies show a higher incidence of rheumatic autoimmune diseases among adult patients with MS or NMO and their families, but there are no studies in the pediatric population. To evaluate an association of MS and NMO with autoimmune rheumatic diseases in pediatric patients. 22 patients younger than 21 years old with MS or NMO diagnosed before the age of 18 years were evaluated regarding epidemiological data, clinical presentation, association with autoimmune diseases, family history of autoimmune diseases, laboratory findings, imaging studies and presence of auto-antibodies. Among the patients studied, there was a prevalence of females (68.1%). The mean age of symptoms onset was 8 years and 9 months and the mean current age was 16 years and 4 months. Two patients (9%) had a history of associated autoimmune rheumatic disease: one case of juvenile dermatomyositis in a patient with NMO and another of systemic lupus erythematosus in a patient with MS. Three patients (13%) had a family history of autoimmunity in first-degree relatives. Antinuclear antibody was found positive in 80% of patients with NMO and 52% of patients with MS. About 15% of antinuclear antibody-positive patients were diagnosed with rheumatologic autoimmune diseases. Among patients with demyelinating diseases diagnosed in childhood included in this study there was a high frequency of antinuclear antibody positivity but a lower association with rheumatologic autoimmune diseases than that observed in studies conducted in adults. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Mucosal healing effect of mesalazine granules in naproxen-induced small bowel enteropathy

PubMed Central

Rácz, István; Szalai, Milán; Kovács, Valéria; Regőczi, Henriett; Kiss, Gyöngyi; Horváth, Zoltán

2013-01-01

AIM: To investigate the effect of mesalazine granules on small intestinal injury induced by naproxen using capsule endoscopy (CE). METHODS: This was a single center, non-randomized, open-label, uncontrolled pilot study, using the PillCam SB CE system with RAPID 5 software. The Lewis Index Score (LIS) for small bowel injury was investigated to evaluate the severity of mucosal injury. Arthropathy patients with at least one month history of daily naproxen use of 1000 mg and proton pump inhibitor co-therapy were screened. Patients with a minimum LIS of 135 were eligible to enter the 4-wk treatment phase of the study. During this treatment period, 3 × 1000 mg/d mesalazine granules were added to ongoing therapies of 1000 mg/d naproxen and 20 mg/d omeprazole. At the end of the 4-wk combined treatment period, a second small bowel CE was performed to re-evaluate the enteropathy according to the LIS results. The primary objective of this study was to assess the mucosal changes after 4 wk of mesalazine treatment. RESULTS: A total of 18 patients (16 females), ranging in age from 46 to 78 years (mean age 60.3 years) were screened, all had been taking 1000 mg/d naproxen for at least one month. Eight patients were excluded from the mesalazine therapeutic phase of the study for the following reasons: the screening CE showed normal small bowel mucosa or only insignificant damages (LIS < 135) in five patients, the screening esophagogastroduodenoscopy revealed gastric ulcer in one patient, capsule technical failure and incomplete CE due to poor small bowel cleanliness in two patients. Ten patients (9 female, mean age 56.2 years) whose initial LIS reached mild and moderate-to-severe enteropathy grades (between 135 and 790 and ≥ 790) entered the 4-wk therapeutic phase and a repeat CE was performed. When comparing the change in LIS from baseline to end of treatment in all patients, a marked decrease was seen (mean LIS: 1236.4 ± 821.9 vs 925.2 ± 543.4, P = 0.271). Moreover, a

Autoimmune diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS).

PubMed

Holmqvist, Anna Sällfors; Olsen, Jørgen H; Mellemkjaer, Lene; Garwicz, Stanislaw; Hjorth, Lars; Moëll, Christian; Månsson, Bengt; Tryggvadottir, Laufey; Hasle, Henrik; Winther, Jeanette Falck

2016-09-01

The pattern of autoimmune diseases in childhood cancer survivors has not been investigated previously. We estimated the risk for an autoimmune disease after childhood cancer in a large, population-based setting with outcome measures from comprehensive, nationwide health registries. From the national cancer registries of Denmark, Iceland and Sweden, we identified 20 361 1-year survivors of cancer diagnosed before the age of 20 between the start of cancer registration in the 1940s and 1950s through 2008; 125 794 comparison subjects, matched by age, gender and country, were selected from national population registers. Study subjects were linked to the national hospital registers. Standardised hospitalisation rate ratios (SHRRs) and absolute excess risks (AERs) were calculated. Childhood cancer survivors had a significantly increased SHRR of 1.4 (95% CI 1.3 to 1.5) of all autoimmune diseases combined, corresponding to an AER of 67 per 100 000 person-years. The SHRRs were significantly increased for autoimmune haemolytic anaemia (16.3), Addison's disease (13.9), polyarteritis nodosa (5.8), chronic rheumatic heart disease (4.5), localised scleroderma (3.6), idiopathic thrombocytopenic purpura (3.4), Hashimoto's thyroiditis (3.1), pernicious anaemia (2.7), sarcoidosis (2.2), Sjögren's syndrome (2.0) and insulin-dependent diabetes mellitus (1.6). The SHRRs for any autoimmune disease were significantly increased after leukaemia (SHRR 1.6), Hodgkin's lymphoma (1.6), renal tumours (1.6) and central nervous system neoplasms (1.4). Childhood cancer survivors are at increased risk for certain types of autoimmune diseases. These findings underscore the need for prolonged follow-up of these survivors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

Anti-Transglutaminase 6 Antibodies in Children and Young Adults with Cerebral Palsy

PubMed Central

Stenberg, Reidun; Hadjivassiliou, Marios; Aeschlimann, Pascale; Hoggard, Nigel; Aeschlimann, Daniel

2014-01-01

Objectives. We have previously reported a high prevalence of gluten-related serological markers (GRSM) in children and young adults with cerebral palsy (CP). The majority had no enteropathy to suggest coeliac disease (CD). Antibodies against transglutaminase 6 (anti-TG6) represent a new marker associated with gluten-related neurological dysfunction. The aim of this study was to investigate the prevalence of anti-TG6 antibodies in this group of individuals with an early neurological injury resulting in CP. Materials and Methods. Sera from 96 patients with CP and 36 controls were analysed for IgA/IgG class anti-TG6 by ELISA. Results. Anti-TG6 antibodies were found in 12/96 (13%) of patients with CP compared to 2/36 (6%) in controls. The tetraplegic subgroup of CP had a significantly higher prevalence of anti-TG6 antibodies 6/17 (35%) compared to the other subgroups and controls. There was no correlation of anti-TG6 autoantibodies with seropositivity to food proteins including gliadin. Conclusions. An early brain insult and associated inflammation may predispose to future development of TG6 autoimmunity. PMID:24804082

Detection of Celiac Disease and Lymphocytic Enteropathy by Parallel Serology and Histopathology in a Population-Based Study

PubMed Central

Walker, Marjorie M.; Murray, Joseph A.; Ronkainen, Jukka; Aro, Pertti; Storskrubb, Tom; D’Amato, Mauro; Lahr, Brian; Talley, Nicholas J.; Agreus, Lars

2010-01-01

Background & Aims Although serological analysis is used in diagnosis of celiac disease, histopathology is considered most reliable. We performed a prospective study to determine the clinical, pathological and serological spectrum of celiac disease in a general population (Kalixanda study). Methods A random sample of an adult general population (n=1000) was analyzed by upper endoscopy, duodenal biopsy, and serological analysis of tissue transglutaminase (tTg) levels; endomysial antibody (EMA) levels were analyzed in samples that were tTg+. The cutoff values for diagnosis of celiac disease were villous atrophy with 40 intraepithelial lymphocytes (IELs)/100 enterocytes (ECs). Results Samples from 33 subjects were tTg+ and 16 were EMA+. Histological analysis identified 7/1000 subjects (0.7%) with celiac disease; all were tTg+ and 6/7 were EMA+. Another 26 subjects were tTg+ (7/26 EMA+). This was addressed by a second quantitative pathology study, (nested case-control design) using a threshold of 25 IELS/100 ECs. In this analysis, all 13 samples that were tTg+ and EMA+ had ≥25 IELs/100ECs. In total, 16 subjects (1.6%) had serological and histological evidence of gluten-sensitive enteropathy. IELs were quantified in duodenal biopsy samples from seronegative individuals (n=500); 19 (3.8%) had >25 IELs and lymphocytic duodenosis (LD). Conclusions Measurement of ≥25 IELs/100 ECs correlated with serological indicators of celiac disease; a higher IEL threshold could miss 50% of cases. Quantification of tTg is a sensitive test for celiac disease; diagnosis can be confirmed by observation of ≥25 IELs/100ECs in duodenal biopsies. Lymphocytic enteropathy (celiac disease and LD) is common in the population (5.4%). PMID:20398668

Autoantibody Profiling in a Cohort of Pediatric and Adult Patients With Autoimmune Hepatitis.

PubMed

Villalta, Danilo; Girolami, Elia; Alessio, Maria Grazia; Sorrentino, Maria Concetta; Tampoia, Marilina; Brusca, Ignazio; Daves, Massimo; Porcelli, Brunetta; Barberio, Giuseppina; Conte, Mariaelisabetta; Pantarotto, Lisa; Bizzaro, Nicola

2016-01-01

Autoimmune hepatitis (AIH) is a rare condition characterized by the presence of autoantibodies distinctive of type 1 AIH (AIH-1) and type 2 AIH (AIH-2). The aim of this study was to evaluate the autoantibody profile in a cohort of pediatric and adult AIH patients, using both indirect immunofluorescence (IIF) and a new multiplexed line-blot assay. Sera from 63 pediatric and 53 adult AIH patients were tested for antinuclear (ANA), antismooth muscle (SMA), anti-liver kidney microsome 1 (anti-LKM1), anti-liver cytosol 1 (anti-LC1) autoantibodies using IIF methods; for anti-LKM1, anti-LC1, and soluble liver antigen/liver-pancreas (anti-SLA/LP) autoantibodies using the line-blot; for anti-F-actin autoantibodies using IIF both on VSM47 cell-line and on rat intestinal epithelial cells. AIH-1 was the most common type of AIH in the adult cohort (73.6%), while AIH-2 was the most common AIH in the pediatric cohort (61.9%). Both in adult and pediatric AIH-2 anti-LKM1 were the prevalent autoantibodies. In pediatric AIH-2 anti-LC1 autoantibodies were more frequent than in adult AIH-2 (59 vs. 28.6%), and in 35.9% of cases they were present alone. In 17 patients anti-LC1 autoantibodies were detected only with the line-blot assay. The levels of anti-LKM1 and of anti-LC1 were not different between adult and pediatric AIH, and the overall agreement between the results obtained with the two IIF methods for F-actin detection was 98.8% (CI 95%: 94.4-99.7%). The line-blot assay showed a higher sensitivity than IIF for anti-LC1 detection. Anti-LKM1 and anti-LC1 autoantibody levels are not different in adults and children. An almost perfect agreement between the two IIF methods for anti-F-actin detection has been observed. © 2014 Wiley Periodicals, Inc.

[Allergy and autoimmunity: Molecular diagnostics, therapy, and presumable pathogenesis].

PubMed

Arefieva, A S; Smoldovskaya, O V; Tikhonov, A A; Rubina, A Yu

2017-01-01

Allergic and autoimmune diseases represent immunopathological reactions of an organism to antigens. Despite that the allergy is a result of exaggerated immune response to foreign antigens (allergens) and autoimmune diseases are characterized by the pathological response to internal antigens (autoantigens), the underlying mechanisms of these diseases are probably common. Thus, both types of diseases represent variations in the hypersensitivity reaction. A large percentage of both the adult and pediatric population is in need of early diagnostics of these pathologies of the immune system. Considering the diversity of antibodies produced in allergic and autoimmune disease and the difficulties accompanying clinical diagnosing, molecular diagnostics of these pathological processes should be carried out in several stages, including screening and confirmatory studies. In this review, we summarize the available data on the molecular diagnostics and therapy of allergic and autoimmune diseases and discuss the basic similarities and differences in the mechanisms of their development.

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

Spontaneous autoimmune reactions against pancreatic islets in mouse strains with generalized autoimmune disease.

PubMed

Kolb, H; Freytag, G; Kiesel, U; Kolb-Bachofen, V

1980-09-01

The spontaneously autoimmune mouse strains NZB, NZB X NZW, MRL and BXSB have been examined for signs of autoimmune reactions against islet cells. Between 15 and 55 animals of each strain were tested. Infiltrates of lymphocytes and fibroblasts into pancreatic islets were found in more than 80% of NZB mice, in about 50% of MRL and NZB X NZW mice, and in less than 20% of BXSB mice. Infiltrates were not found in the exocrine portion of pancrea. All NZB mice had abnormal glucose tolerance. In the three other strains between 20 and 50% of animals had abnormal glucose tolerance. All mice had fasting normoglycaemia. The lesions in NZB mice were studied in more detail. It was found by ultrastructural analysis that in young mice pancreatic infiltrates consisted of lymphocytes and fibroblasts. Single lymphocytes were also seen outside the main infiltration area. After 2 to 5 months of age another type of infiltrate, consisting of lymphocytes and macrophages was observed. B-cell destruction by lymphocytes was apparent in both young and adult NZB mice. It is concluded that cellular autoimmune reactions against pancreatic islets may occur spontaneously as a consequence of immunological disorders in NZB, NZB X NZW and MRL mice.

Treatment of Children with Protein – Losing Enteropathy After Fontan and Other Complex Congenital Heart Disease Procedures in Condition with Limited Human and Technical Resources

PubMed Central

Bejiqi, Ramush; Retkoceri, Ragip; Zeka, Naim; Bejiqi, Hana; Vuqiterna, Armend; Maloku, Arlinda

2014-01-01

Background Protein-losing enteropathy (PLE) is a disorder characterized by abnormal and often profound enteric protein loss. It’s relatively uncommon complication of Fontan and other complex congenital heart disease (CCHD) procedures. Because of the complexity and rarity of this disease process, the pathogenesis and pathophysiology of protein-losing enteropathy remain poorly understood, and attempts at treatment seldom yield long-term success. Aim of presentation is to describe single centre experience in diagnosis, evaluation, management and treatment of children with protein-losing enteropathy after Fontan and other CCHD procedures in the current era and in centre with limited human and technical resources, follows with a comprehensive review of protein-losing enteropathy publications, and concludes with suggestions for prevention and treatment. Material and methodology Retrospectively we analyzed patients with CCHD and protein-losing enteropathy in our institution, starting from January 2000 to December 2012. The including criteria were age between two and 17 years, to have a complex congenital heart disease and available complete documentation of cardiac surgery under cardiopulmonary bypass. Results Of all patients we evaluated 18 cases with protein-losing enteropathy, aged 6 to 19 years (mean 14±9); there were three children who had undergone screening procedure for D-transposition, one Tetralogy of Fallot, and remaining 14 patients had undergone Fontan procedures; (anatomic diagnosis are: six with tricuspid atresia, seven with d-transposition, double outlet right ventricle and pulmonary atresia and two with hypoplastic left heart syndrome). The diagnosis of protein-losing enteropathy was made at median age of 5.6 years, ranging from 13 months to 15 years. Diagnosis was made using alpha 1-antitrypsin as a gold marker in stool. By physical examination in 14 patients edema was found, in three ascites, and six patients had pleural effusion. Laboratory findings

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

Similarities and differences between older and young adult patients with celiac disease.

PubMed

Kalkan, Çağdaş; Karakaya, Fatih; Soykan, Irfan

2017-11-01

Celiac disease is an autoimmune enteropathy with variable clinical symptoms. Elderly patients can have different manifestations from those of young patients. The aims of the present study were to investigate whether any differences or similarities exist between older and young patients with celiac disease with a special emphasis on concurrent autoimmune diseases. Celiac disease patients were stratified as older and younger patients. These two groups were then compared by means of clinical symptoms, laboratory parameters and concurrent autoimmune diseases. Factors associated with the presence of an autoimmune disease were identified by univariate and multivariate analysis. There were 66 older patients (mean age 67.7 ± 3.2 years, 50 women), and 277 younger patients (mean age 35.9 ± 11.7 years, 207 women). Of the 66 older patients, eight patients had gastrointestinal symptoms and 58 patients had extradigestive symptoms. In the younger group, the number of patients referred due to gastrointestinal symptoms was higher (8 [12.2%] vs 200 (72.2%), P < 0.001) compared with the older group. Whereas 10 (15.1%) older patients showed polyautoimmunity, 55 (19.8%) younger patients had polyautoimmunity. Multiple autoimmune syndrome was more common in older patients compared with young patients (31 [47%] vs 12 [4%], P < 0.001, respectively). The presentation of celiac disease clinically, histologically and by means of laboratory parameters is different in older and young patients. Polyautoimmunity and multiple autoimmune syndrome are more common in older patients compared with younger patients. A biopsy score of Marsh score type, antinuclear antibody positivity, high serum anti-tissue transglutaminase immunoglobulin A level and low hemoglobin level were risk factors for having an autoimmune disease. Geriatr Gerontol Int 2017; 17: 2060-2067. © 2017 Japan Geriatrics Society.

Coexistence of adult-onset Still's disease and autoimmune hyperthyroidism in a patient who responded to corticosteroids and β-blocker.

PubMed

Chen, Hsiao-Shuang; Yu, Kuang-Hui; Ho, Huei-Huang

2010-12-01

The pathogenesis of adult-onset Still's disease (AOSD), which is currently thought to be an autoimmune disorder, may share similarities with autoimmune hyperthyroidism. This report describes a middle-aged woman in whom hyperthyroidism and Still's disease developed concurrently. During the course of her illness, the hyperthyroidism was observed to be aggravated whenever her AOSD was in the active stage. After her AOSD activity was controlled, her hyperthyroidism improved clinically. The extent of activation of her hyperthyroidism was observed in parallel to the extent of activation of her AOSD. Furthermore, the patient developed neutropenia after receiving either propylthiouracil (PTU) or methimazole, both of which are standard accepted medications for treatment of hyperthyroidism. Immune mechanisms contributed to PTU induced neutropenia have been proposed, and hyperthyroid patients treated with standard antithyroid agents should be monitored for blood cell counts especially for AOSD patients. Corticosteroid may effect Graves' disease activity, and steroids may play a role in the treatment of hyperthyroidism if a patient had drug allergies to antithyroid agents.

[Autoimmune hepatitis].

PubMed

Ostojić, Rajko

2003-01-01

Autoimmune hepatitis is an unresolving, hepatocellular inflammation of unknown cause that is characterized by the presence of periportal hepatitis on histologic examination, tissue autoantibodies in serum, and hypergammaglobulinemia. By international consensus, the designation autoimmune hepatitis has replaced alternative terms for the condition. Three types of autoimmune hepatitis have been proposed based on immunoserologic findings. Type 1 autoimmune hepatitis is characterized by the presence of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) (or both) in serum. Seventy percent of patients with type 1 of autoimmune hepatitis are women. This type is the most common form and accounts for at least 80% of cases. Type 2 is characterized by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) in serum. Patients with this type of autoimmune hepatitis are predominantly children. Type 3 autoimmune hepatitis is characterized by the presence of antibodies to soluble liver antigen (anti-SLA) in serum. There are no individual features that are pathognomonic of autoimmune hepatitis, and its diagnosis requires the confident exclusion of other conditions. The large majority of patients show satisfactory response to corticosteroid (usually prednisone or prednisolone) therapy. For the past 30 years it has been customary to add azathioprine as a "steroid sparing" agent to allow lower doses of steroids to be used and remission, once achieved, can be sustained in many patients with azathioprine alone after steroid withdrawal. Patients with autoimmune hepatitis who have decompensated during or after corticosteroid therapy are candidates for liver transplantation.

Role of autoimmunity in nonviral chronic liver disease.

PubMed

Amarapurkar, D N; Amarapurkar, A D

2000-11-01

To evaluate the prevalence and clinical profile of autoimmune hepatitis (AIH) in patients with chronic liver disease. Four hundred and thirty five consecutive patient with chronic liver disease seen in our department from January 1997 to December 1998 were studied with detailed history and clinical examination. All the patients underwent liver function tests, ultrasonography, isotope liver scanning, viral markers, autoimmune markers ANA, ASMA, LKM1 and AMA (by immunofluorescence technique) and liver histology whenever permissible. Appropriate work up for Wilson's disease was done whenever suspected clinically. Diagnosis of autoimmune hepatitis was made by the composite scoring system by international autoimmune hepatitis group. Twenty out of the 435 patients met the criteria of definite autoimmune hepatitis and seven patient had probable autoimmune hepatitis. Forty out of 408 patients showed markers of autoimmunity positive but did not qualify diagnosis of AIH on composite scores. Demographic profile of 27 patients with autoimmune hepatitis was as follows; male:female ratio 1:8, mean age 39.8 +/- 13 years (Range 4-65 years); mode of presentation as cirrhosis 11/27 (40.7%), chronic hepatitis 12/27 (44.4%) and acute hepatitis 4/27 (14.8%). Elevated serum bilirubin levels were seen in 12 (44.4%) patients while mean serum aminotransferases levels were 249 +/- 343 and 262 +/- 418 respectively. Other disease associations seen were as follows: diabetes in 4 (14.8%), rheumatoid arthritis in 3 (11%), hypothyroidism in 2 (7.4%) and ulcerative colitis in 1 (3.7%). The pattern of autoimmune markers was ANA +ve 23/27 (85%) (+ve titres of ANA > 1:80 in adults and 1:20 in children), ASMA +ve in 16/27 (59.2%) (+ve titres of ASMA > 1:40) and LKM1 in 3 patients. AMA in tires less than 1:80 was found in 3 patients. Liver histology changes seen were lymphoplasmacytic infiltrates (100%), bridging necrosis (93%), liver cell rossetting (80%) and fibrosis with or without cirrhosis (50

Pattern-recognition receptors: signaling pathways and dysregulation in canine chronic enteropathies-brief review.

PubMed

Heilmann, Romy M; Allenspach, Karin

2017-11-01

Pattern-recognition receptors (PRRs) are expressed by innate immune cells and recognize pathogen-associated molecular patterns (PAMPs) as well as endogenous damage-associated molecular pattern (DAMP) molecules. With a large potential for synergism or convergence between their signaling pathways, PRRs orchestrate a complex interplay of cellular mediators and transcription factors, and thus play a central role in homeostasis and host defense. Aberrant activation of PRR signaling, mutations of the receptors and/or their downstream signaling molecules, and/or DAMP/PAMP complex-mediated receptor signaling can potentially lead to chronic auto-inflammatory diseases or development of cancer. PRR signaling pathways appear to also present an interesting new avenue for the modulation of inflammatory responses and to serve as potential novel therapeutic targets. Evidence for a dysregulation of the PRR toll-like receptor (TLR)2, TLR4, TLR5, and TLR9, nucleotide-binding oligomerization domain-containing protein (NOD)2, and the receptor of advanced glycation end products (RAGE) exists in dogs with chronic enteropathies. We describe the TLR, NOD2, and RAGE signaling pathways and evaluate the current veterinary literature-in comparison to human medicine-to determine the role of TLRs, NOD2, and RAGE in canine chronic enteropathies.

Galectin-3 in autoimmunity and autoimmune diseases

PubMed Central

de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo

2015-01-01

Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell–cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte–macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. PMID:26142116

Sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes.

PubMed

Löfvenborg, Josefin E; Andersson, Tomas; Carlsson, Per-Ola; Dorkhan, Mozhgan; Groop, Leif; Martinell, Mats; Tuomi, Tiinamaija; Wolk, Alicja; Carlsson, Sofia

2016-12-01

Sweetened beverage intake is associated with increased risk of type 2 diabetes, but its association with autoimmune diabetes is unclear. We aimed to investigate sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA); autoimmune diabetes with features of type 2 diabetes. Data from a Swedish population-based study was used, including incident cases of LADA (n = 357) and type 2 diabetes (n = 1136) and randomly selected controls (n = 1371). Diabetes classification was based on onset age (≥35), glutamic acid decarboxylase autoantibodies (GADA) and C-peptide. Sweetened beverage intake information was derived from a validated food frequency questionnaire. ORs adjusted for age, sex, family history of diabetes, education, lifestyle, diet, energy intake and BMI were estimated using logistic regression. Daily intake of >2 servings of sweetened beverages (consumed by 6% of participants) was associated with increased risk of LADA (OR: 1.99, 95% CI: 1.11-3.56), and for each 200 mL daily serving, OR was 1.15 (95% CI: 1.02-1.29). Findings were similar for sugar-sweetened (OR: 1.18, 95% CI: 1.00-1.39) and artificially sweetened beverages (OR: 1.12, 95% CI: 0.95-1.32). Similarly, each daily serving increment in total sweetened beverage conferred 20% higher type 2 diabetes risk (95% CI: 1.07-1.34). In type 2 diabetes patients, high consumers displayed higher HOMA-IR levels (4.5 vs 3.5, P = 0.0002), but lower HOMA-B levels (55 vs 70, P = 0.0378) than non-consumers. Similar tendencies were seen in LADA. High intake of sweetened beverages was associated with increased risk of LADA. The observed relationship resembled that with type 2 diabetes, suggesting common pathways possibly involving insulin resistance. © 2016 European Society of Endocrinology.

Alcohol and the risk for latent autoimmune diabetes in adults: results based on Swedish ESTRID study.

PubMed

Rasouli, Bahareh; Andersson, Tomas; Carlsson, Per-Ola; Dorkhan, Mozhgan; Grill, Valdemar; Groop, Leif; Martinell, Mats; Tuomi, Tiinamaja; Carlsson, Sofia

2014-11-01

Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. Our aim was to investigate whether alcohol consumption is associated with the risk of latent autoimmune diabetes in adults (LADA), an autoimmune form of diabetes with features of type 2 diabetes. A population-based case-control study was carried out to investigate the association of alcohol consumption and the risk of LADA. We used data from the ESTRID case-control study carried out between 2010 and 2013, including 250 incident cases of LADA (glutamic acid decarboxylase antibodies (GADAs) positive) and 764 cases of type 2 diabetes (GADA negative), and 1012 randomly selected controls aged ≥35. Logistic regression was used to estimate the odds ratios (ORs) of diabetes in relation to alcohol intake, adjusted for age, sex, BMI, family history of diabetes, smoking, and education. Alcohol consumption was inversely associated with the risk of type 2 diabetes (OR 0.95, 95% CI 0.92-0.99 for every 5-g increment in daily intake). Similar results were observed for LADA, but stratification by median GADA levels revealed that the results only pertained to LADA with low GADA levels (OR 0.85, 95% CI 0.76-0.94/5 g alcohol per day), whereas no association was observed with LADA having high GADA levels (OR 1.00, 95% CI 0.94-1.06/5 g per day). Every 5-g increment of daily alcohol intake was associated with a 10% increase in GADA levels (P=0.0312), and a 10% reduction in homeostasis model assessment of insulin resistance (P=0.0418). Our findings indicate that alcohol intake may reduce the risk of type 2 diabetes and type 2-like LADA, but has no beneficial effects on diabetes-related autoimmunity. © 2014 The authors.

Gut microbiota in autoimmunity: potential for clinical applications.

PubMed

Kim, Donghyun; Yoo, Seung-Ah; Kim, Wan-Uk

2016-11-01

Microbial habitation in the human body begins immediately after birth, and adults are colonized by microbes outnumbering human cells by a factor of ten. Especially, intestinal track is a living space for diverse microbial species that have coevolved symbiotically. A principal function of the gut microbiota is to protect the host from harmful bacteria and to provide benefits for the host through several mechanisms, including direct competition for limited nutrients, training of host immune systems to recognize specifically foreign materials and conversion of otherwise indigestible food into energy and absorbable nutrients. Therefore, gut dysbiosis, a bacterial imbalance state, is related with the pathogenesis of various host diseases including autoimmune diseases. In the current review, we highlight the importance of gut microbiota in the normal health and autoimmune diseases. We also discuss regulation of gut dysbiosis and future direction for potential clinical applications, including treatment and diagnostics of autoimmune diseases.

Clinical and metabolic profile of patients with latent autoimmune diabetes in adults in specialized care in Madrid.

PubMed

Arranz Martín, Alfonso; Lecumberri Pascual, Edurne; Brito Sanfiel, Miguel Ángel; Andía Melero, Víctor; Nattero Chavez, Lia; Sánchez López, Iván; Cánovas Molina, Gloria; Arrieta Blanco, Francisco; González Perez Del Villar, Noemí

2017-01-01

To report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. Patients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed. Number of patients; 193; 56% females. Family history of DM: 62%. Age at DM diagnosis: 49years. Delay in confirmation of LADA: 3.5years. Insulin-independence time: 12months. Baseline serum C-peptide levels: 0.66ng/ml. Basal-bolus regimen: 76.7%. Total daily dose: 35.1U/day, corresponding to 0.51U/Kg. With no associated oral antidiabetic drugs: 33.5%. Other autoimmune diseases: 57%. Fasting plasma glucose: 160.5mg/dL. HbA1c: 7.7%. BMI: 25.4kg/m 2 (overweight, 31.5%; obesity, 8%). Blood pressure: 128/75. HDL cholesterol: 65mg/dL. LDL cholesterol: 96mg/dL. Triglycerides: 89mg/dL. Known chronic complications: 28%. Recognition of LADA may be delayed by several years. There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters. Most patients are poorly controlled despite intensive insulin therapy. They often have overweight, but have adequate control of BP and lipid profile and a low incidence of macrovascular complications. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

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

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.

Successful diuretics treatment of protein-losing enteropathy in Noonan syndrome.

PubMed

Mizuochi, Tatsuki; Suda, Kenji; Seki, Yoshitaka; Yanagi, Tadahiro; Yoshimoto, Hironaga; Kudo, Yoshiyuki; Iemura, Motofumi; Tanikawa, Ken; Matsuishi, Toyojiro

2015-04-01

There are few reports on successful high-dose spironolactone treatment of refractory protein-losing enteropathy (PLE) caused by Fontan procedure. We report successful diuretics treatment with spironolactone and furosemide at standard dose, of refractory PLE in a patient with Noonan syndrome and repaired congenital heart disease. This is the first successful application of diuretics treatment in a patient with refractory PLE without Fontan procedure. This case illustrates that diuretics treatment can be the first-line treatment of PLE regardless of the causative physiology, and can be effective in refractory PLE with Noonan syndrome. © 2015 Japan Pediatric Society.

Pharmacologic targeting of bacterial β-glucuronidase alleviates nonsteroidal anti-inflammatory drug-induced enteropathy in mice.

PubMed

LoGuidice, Amanda; Wallace, Bret D; Bendel, Lauren; Redinbo, Matthew R; Boelsterli, Urs A

2012-05-01

Small intestinal mucosal injury is a frequent adverse effect caused by nonsteroidal anti-inflammatory drugs (NSAIDs). The underlying mechanisms are not completely understood, but topical (luminal) effects have been implicated. Many carboxylic acid-containing NSAIDs, including diclofenac (DCF), are metabolized to acyl glucuronides (AGs), and/or ether glucuronides after ring hydroxylation, and exported into the biliary tree. In the gut, these conjugates are cleaved by bacterial β-glucuronidase, releasing the potentially harmful aglycone. We first confirmed that DCF-AG was an excellent substrate for purified Escherichia coli β-D-glucuronidase. Using a previously characterized novel bacteria-specific β-glucuronidase inhibitor (Inhibitor-1), we then found that the enzymatic hydrolysis of DCF-AG in vitro was inhibited concentration dependently (IC₅₀ ∼164 nM). We next hypothesized that pharmacologic inhibition of bacterial β-glucuronidase would reduce exposure of enterocytes to the aglycone and, as a result, alleviate enteropathy. C57BL/6J mice were administered an ulcerogenic dose of DCF (60 mg/kg i.p.) with or without oral pretreatment with Inhibitor-1 (10 μg per mouse, b.i.d.). Whereas DCF alone caused the formation of numerous large ulcers in the distal parts of the small intestine and increased (2-fold) the intestinal permeability to fluorescein isothiocyanate-dextran, Inhibitor-1 cotreatment significantly alleviated mucosal injury and reduced all parameters of enteropathy. Pharmacokinetic profiling of DCF plasma levels in mice revealed that Inhibitor-1 coadministration did not significantly alter the C(max), half-life, or area under the plasma concentration versus time curve of DCF. Thus, highly selective pharmacologic targeting of luminal bacterial β-D-glucuronidase by a novel class of small-molecule inhibitors protects against DCF-induced enteropathy without altering systemic drug exposure.

Pharmacologic Targeting of Bacterial β-Glucuronidase Alleviates Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy in Mice

PubMed Central

LoGuidice, Amanda; Wallace, Bret D.; Bendel, Lauren; Redinbo, Matthew R.

2012-01-01

Small intestinal mucosal injury is a frequent adverse effect caused by nonsteroidal anti-inflammatory drugs (NSAIDs). The underlying mechanisms are not completely understood, but topical (luminal) effects have been implicated. Many carboxylic acid-containing NSAIDs, including diclofenac (DCF), are metabolized to acyl glucuronides (AGs), and/or ether glucuronides after ring hydroxylation, and exported into the biliary tree. In the gut, these conjugates are cleaved by bacterial β-glucuronidase, releasing the potentially harmful aglycone. We first confirmed that DCF-AG was an excellent substrate for purified Escherichia coli β-d-glucuronidase. Using a previously characterized novel bacteria-specific β-glucuronidase inhibitor (Inhibitor-1), we then found that the enzymatic hydrolysis of DCF-AG in vitro was inhibited concentration dependently (IC50 ∼164 nM). We next hypothesized that pharmacologic inhibition of bacterial β-glucuronidase would reduce exposure of enterocytes to the aglycone and, as a result, alleviate enteropathy. C57BL/6J mice were administered an ulcerogenic dose of DCF (60 mg/kg i.p.) with or without oral pretreatment with Inhibitor-1 (10 μg per mouse, b.i.d.). Whereas DCF alone caused the formation of numerous large ulcers in the distal parts of the small intestine and increased (2-fold) the intestinal permeability to fluorescein isothiocyanate-dextran, Inhibitor-1 cotreatment significantly alleviated mucosal injury and reduced all parameters of enteropathy. Pharmacokinetic profiling of DCF plasma levels in mice revealed that Inhibitor-1 coadministration did not significantly alter the Cmax, half-life, or area under the plasma concentration versus time curve of DCF. Thus, highly selective pharmacologic targeting of luminal bacterial β-d-glucuronidase by a novel class of small-molecule inhibitors protects against DCF-induced enteropathy without altering systemic drug exposure. PMID:22328575

Clinical significance of autoantibodies in autoimmune hepatitis.

PubMed

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

2013-10-01

The accurate diagnosis and classification of autoimmune hepatitis (AIH) rely upon the detection of characteristic autoantibodies. Positivity for anti-nuclear (ANA) and/or anti-smooth muscle (SMA) autoantibodies defines AIH type 1 (AIH-1), whereas anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) define AIH type 2 (AIH-2). ANA and SMA, and less commonly anti-LKM1, have also been detected in de-novo autoimmune hepatitis developing after liver transplantation, a condition that may affect patients transplanted for non-autoimmune liver disease. The diagnostic autoantibodies associated with AIH-1 are also detected in the paediatric AIH/sclerosing cholangitis overlap syndrome, referred to as autoimmune sclerosing cholangitis (ASC). ASC, like adult primary sclerosing cholangitis, is often associated with atypical perinuclear anti-neutrophil cytoplasmic autoantibodies (p-ANCA), although p-ANCA are also detected in other autoimmune liver diseases. These associations highlight the necessity for simple and prompt diagnostic autoantibody testing, and the requirement for the accurate interpretation of the results of the tests in the clinical context. Fine-mapping of antigenic autoantibody targets has facilitated the development of rapid molecular assays that have the potential to revolutionise the field if properly standardised and when used in combination with classical immunofluorescence. Despite their diagnostic significance, the pathogenic role of the various autoantibodies and the mechanisms by which they can potentially inflict damage onto the liver cell remain a topic for further research. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Difference in target antigens between central tolerance and peripheral tolerance deficiencies].

PubMed

Chida, Natsuko; Kobayashi, Ichiro

2015-01-01

Failure of the immunotolerance mechanisms causes multiple organ-specific autoimmune disorders. Mutations of autoimmune regulator (AIRE) gene result in central immunotolerance deficiency named autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED). Mutations of FOXP3 genes cause regulatory T cell (Treg) deficiency named immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Because T cell tolerance influences B cell tolerance, autoantibodies seem to reflect the presence of autoreactive T cells with the same antigen specificity. To date many differences in both clinical features and autoantibody profiles have been described between APECED and IPEX syndrome. In addition to the differences in target organs, we have found differences in the target antigens in the same organ, small intestine, between both disorders; anti-autoimmune enteropathy-related 75 kDa antigen (AIE-75) antibodies are specific to IPEX syndrome, whereas anti-tryptophan hydroxylase-1 (TPH-1) antibodies are specific to APECED. These facts suggest that immunotolerance to AIE-75 depends on the Treg, whereas the tolerance to TPH-1 depends on the central mechanisms. Furthermore, given the earlier onset and more serious clinical features of IPEX syndrome than APECED, physiological roles of Aire on the selection of Treg may be, if present, limited.

Thyroid-associated orbitopathy is linked to gastrointestinal autoimmunity

PubMed Central

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

2014-01-01

Common autoimmune disorders tend to co-exist in the same subjects and cluster in families. The objective of this study was to determine the prevalence of autoimmune co-morbidity in patients with autoimmune thyroid disease (AITD) with and without thyroid-associated orbitopathy (TAO). This was a cross-sectional study conducted at an academic tertiary referral centre. Of 1310 patients with AITD [n = 777 or 59% with Graves' disease (GD) and n = 533, 41% with Hashimoto's thyroiditis (HT)] followed at a specialized joint thyroid–eye out-patient clinic, 176 (13·4%) had an adult type of the autoimmune polyglandular syndrome, 129 (9·8%) type 1 diabetes, 111 (8·5%) coeliac disease, 60 (4·6%) type A autoimmune gastritis, 57 (4·4%) vitiligo and 25 (1·9%) Addison's disease. Coeliac disease and autoimmune gastritis were associated positively with GD [odds ratio (OR) = 2·18; P = 0·002 and OR = 6·52; P < 0·001], whereas type 1 diabetes, Addison's disease, autoimmune primary hypogonadism, alopecia areata, rheumatoid arthritis and Sjögren's syndrome were ‘protective’ for GD and thus linked to HT, OR = 0·49 (P < 0·001), 0·06 (P < 0·001), 0·25 (P < 0·001), 0·50 (P = 0·090) and 0·32 (P = 0·003), respectively. Of 610 (46·6%) AITD patients with TAO, 584 (95·7%) and 26 (4·3%) had GD and HT, respectively (P < 0·001). TAO was most prevalent in GD patients with coeliac disease (94%, OR = 1·87, P < 0·001). Multivariate analysis showed high OR for coeliac disease and autoimmune gastritis (3·4 and 4·03, both P < 0·001) pertaining to the association with TAO while type 1 diabetes, Addison's disease and alopecia areata were protective for TAO. In patients with TAO, coeliac disease is the most prevalent co-morbid autoimmune condition and rates are increased compared to GD patients without TAO. PMID:24903731

[Diagnostics and treatment of polyglandular syndrome of adults].

PubMed

Larina, A A; Shapoval'iants, O S; Mazurina, N V; Troshina, E A

2012-01-01

Autoimmune polyendocrine syndromes (APS) are rare endocrinopathies characterized by the coexistence of at least two glandular autoimmune diseases. APS comprise a wide spectrum of autoimmune disorders and are divided into a very rare juvenile (APS type 1) and a more common adult type with (APS 2) or without adrenal failure (APS 3). The first clinical manifestations of APS 1 usually occur in childhood whereas APS 2 mostly occurs during the third and fourth decades of life. The third type has been described in adults that, contrary to types 1 and 2, does not involve the adrenal cortex. No clinical differences between types 2 and 3 have been described except the absence of adrenal failure. Type 4 APS is a rare syndrome characterized by the combination of autoimmune conditions not falling into the above categories. It consists of adrenal failure with one or more minor autoimmune disorders barring major components of type 1 and 2 APS. Usually, autoimmune polyendocrine syndrome of adults manifests itself as one of the major autoimmune diseases (such as adrenal failure, Grave's disease, or type 1 diabetes) and minor autoimmune disorders (vitiligo, alopecia) preceding the development of autoimmune deficiency of major endocrine glands. This article describes a patient with type 3 APS, who developed type 1 diabetes. Grave's disease and vitiligo. The development of the syndrome started from vitiligo in the chidhood. Moreover, the patient suffered primary sterility and presented with progressive diabetic nephropathy of autoimmune origin. It is concluded that patients with a single autoimmune component of polyendocrine syndrome should be screened to exclude other autoimmune endocrine disorders.

Autoimmunity and Gastric Cancer

PubMed Central

Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo

2018-01-01

Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557

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

Autoimmune encephalitis.

PubMed

Newman, M P; Blum, S; Wong, R C W; Scott, J G; Prain, K; Wilson, R J; Gillis, D

2016-02-01

Over the past decade, the clinical spectrum of autoimmune encephalitis has expanded with the emergence of several new clinicopathological entities. In particular, autoimmune encephalitis has recently been described in association with antibodies to surface receptors and ion channels on neurological tissues. Greater clinician awareness has resulted in autoimmune encephalitis being increasingly recognised in patients with unexplained neurological and psychiatric symptoms and signs. The clinical spectrum of presentations, as well as our understanding of disease mechanisms and treatment regimens, is rapidly developing. An understanding of these conditions is important to all subspecialties of Internal Medicine, including neurology and clinical immunology, psychiatry, intensive care and rehabilitation medicine. This review provides a contemporary overview of the aetiology, investigations and treatment of the most recently described autoimmune encephalitides. © 2016 Royal Australasian College of Physicians.

Diffusion and ADC-map images detect ongoing demyelination on subcortical white matter in an adult metachromatic leukodystrophy patient with autoimmune Hashimoto thyroiditis

PubMed Central

Miura, Akiko; Kumabe, Yuri; Kimura, En; Yamashita, Satoshi; Ueda, Akihiko; Hirano, Teruyuki; Uchino, Makoto

2010-01-01

Adult-onset metachromatic leukodystrophy (MLD) often shows schizophrenia- or encephalopathy-like symptoms at an early stage, such as behavioural abnormalities, cognitive impairment, mood disorders and hallucinations. The authors report the case of an adult woman with MLD who had been given antipsychotic medication for schizophrenia. In the differential diagnosis, screening of auto-antibodies was important for ruling out other encephalopathies as she had a euthyroid Hashimoto thyroiditis. Diagnosis was based the results of MRI, nerve conduction velocity, sensory evoked potential, motor evoked potential, lysosomal enzyme activity and gene analysis studies. Brain MRI showed diffuse demyelination spreading from the deep white matter to subcortical area as high signals at the edges of these lesions in diffusion and apparent diffusion coefficient-map images with the U-fibres conserved. The authors diagnosed adult-onset MLD coexisting with euthyroid autoimmune Hashimoto thyroiditis. PMID:22798296

Autoimmune Thyroid Disorders

PubMed Central

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

2013-01-01

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

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

Identification of Unique Antigenic Determinants in the Amino Terminus of IA-2 (ICA512) in Childhood and Adult Autoimmune Diabetes: New Biomarker Development.

PubMed

Acevedo-Calado, Maria; James, Eddie A; Morran, Michael P; Pietropaolo, Susan L; Ouyang, Qin; Arribas-Layton, David; Songini, Marco; Liguori, Marco; Casu, Anna; Auchus, Richard J; Huang, Shuai; Yu, Liping; Michels, Aaron; Gianani, Roberto; Pietropaolo, Massimo

2017-04-01

The characterization of diverse subtypes of diabetes is a dynamic field of clinical research and an active area of discussion. The objective of this study was to identify new antigenic determinants in the neuroendocrine autoantigen IA-2 (ICA512) and assess whether circulating autoantibodies directed to new IA-2 epitopes identify autoimmune diabetes in young and adult populations with diabetes. Clinically diagnosed patients with type 2 diabetes ( n = 258; diabetes duration: 0.01-31 years) were evaluated using a new biomarker detecting autoantibodies directed to the extracellular domain of the neuroendocrine autoantigen IA-2 (IA-2ec). The proportion of IA-2ec autoantibodies was also evaluated in newly diagnosed patients with type 1 diabetes ( n = 150; diabetes duration: 0.04-0.49 years). In addition, IA-2 (intracellular domain), GAD65, and zinc transporter 8 autoantibodies were assayed. IA-2ec autoantibodies were detected in patients with type 1 diabetes and, surprisingly, in 5% of patients with type 2 diabetes without serologic responses to other IA-2 antigenic epitopes or other islet autoantigens. We also assessed the ability of IA-2ec-derived peptides to elicit CD4 + T-cell responses by stimulating peripheral blood mononuclear cells from patients with type 1 diabetes ( n = 18) and HLA-matched healthy subjects ( n = 13) with peptides and staining with the peptide/DQ8-specific tetramers, observing disease-associated responses to previously unreported epitopes within IA-2ec. We developed a new antibody biomarker identifying novel antigenic determinants within the N terminus of IA-2. IA-2ec autoantibodies can be detected in patients with type 1 diabetes and in a subgroup of adult autoimmune patients with type 2 diabetes phenotype negative for conventional islet autoantibody testing. These observations suggest that islet autoimmunity may be more common in clinically diagnosed type 2 diabetes than previously observed. © 2017 by the American Diabetes Association.

Alcohol consumption is associated with reduced risk of Type 2 diabetes and autoimmune diabetes in adults: results from the Nord-Trøndelag health study.

PubMed

Rasouli, B; Ahlbom, A; Andersson, T; Grill, V; Midthjell, K; Olsson, L; Carlsson, S

2013-01-01

We investigated the influence of different aspects of alcohol consumption on the risk of Type 2 diabetes and autoimmune diabetes in adults. We used data from the Nord-Trøndelag Health Survey (HUNT) study, in which all adults aged ≥ 20 years from Nord-Trondelag County were invited to participate in three surveys in 1984-1986, 1995-1997 and 2006-2008. Patients with diabetes were identified using self-reports, and participants with onset age ≥ 35 years were classified as having Type 2 diabetes if they were negative for anti-glutamic acid decarboxylase (n = 1841) and as having autoimmune diabetes if they were positive for anti-glutamic acid decarboxylase (n = 140). Hazard ratios of amount and frequency of alcohol use, alcoholic beverage choice, and binge drinking and alcohol use disorders were estimated. Moderate alcohol consumption (adjusted for confounders) was associated with a reduced risk of Type 2 diabetes in men, but not in women (hazard ratio for men 10-15 g/day 0.48, 95% CI 0.28-0.77; hazard ratio for women ≥ 10 g/day 0.81, 95% CI 0.33-1.96). The reduced risk was primarily linked to consumption of wine [hazard ratio 0.93, 95% CI 0.87-0.99 (per g/day)]. No increased risk was seen in participants reporting binge drinking or in problem drinkers. The results were also compatible with a reduced risk of autoimmune diabetes associated with alcohol consumption [hazard ratio 0.70, 95% CI 0.45-1.08 (frequent consumption) and hazard ratio 0.36, 95% CI 0.13-0.97 (2-7 g/day)]. Moderate alcohol consumption associates with reduced risk of both Type 2 diabetes and autoimmune diabetes. A protective effect of alcohol intake may be limited to men. High alcohol consumption does not seem to carry an increased risk of diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders.

PubMed

Miller, Frederick W; Cooper, Robert G; Vencovský, Jiří; 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 R D J; 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

2013-12-01

To identify new genetic associations with juvenile and adult dermatomyositis (DM). We performed a genome-wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1,178) and controls (n = 4,724). 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. Compared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS-level significance (P < 5 × 10(-8)) at 80 genotyped SNPs. An analysis of 141 non-MHC SNPs previously associated with autoimmune diseases showed that 3 SNPs linked with 3 genes were associated with DM, with a false discovery rate (FDR) of <0.05. These genes were phospholipase C-like 1 (PLCL1; rs6738825, FDR = 0.00089), B lymphoid tyrosine kinase (BLK; rs2736340, FDR = 0.0031), and chemokine (C-C motif) ligand 21 (CCL21; rs951005, FDR = 0.0076). None of these genes was previously reported to be associated with DM. 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. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

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

Intraluminal Administration of Poly I:C Causes an Enteropathy That Is Exacerbated by Administration of Oral Dietary Antigen

PubMed Central

Araya, Romina E.; Jury, Jennifer; Bondar, Constanza

2014-01-01

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen. PMID:24915573

Intraluminal administration of poly I:C causes an enteropathy that is exacerbated by administration of oral dietary antigen.

PubMed

Araya, Romina E; Jury, Jennifer; Bondar, Constanza; Verdu, Elena F; Chirdo, Fernando G

2014-01-01

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen.

Acute Loss of Apolipoprotein E Triggers an Autoimmune Response That Accelerates Atherosclerosis.

PubMed

Centa, Monica; Prokopec, Kajsa E; Garimella, Manasa G; Habir, Katrin; Hofste, Lisa; Stark, Julian M; Dahdah, Albert; Tibbit, Chris A; Polyzos, Konstantinos A; Gisterå, Anton; Johansson, Daniel K; Maeda, Nobuyo N; Hansson, Göran K; Ketelhuth, Daniel F J; Coquet, Jonathan M; Binder, Christoph J; Karlsson, Mikael C I; Malin, Stephen

2018-06-07

Dyslipidemia is a component of the metabolic syndrome, an established risk factor for atherosclerotic cardiovascular disease, and is also observed in various autoimmune and chronic inflammatory conditions. However, there are limited opportunities to study the impact of acquired dyslipidemia on cardiovascular and immune pathology. We designed a model system that allows for the conversion to a state of acute hyperlipidemia in adult life, so that the consequences of such a transition could be observed, through conditionally deleting APOE (apolipoprotein E) in the adult mouse. The transition to hypercholesterolemia was accompanied by adaptive immune responses, including the expansion of T lymphocyte helper cell 1, T follicular helper cell, and T regulatory subsets and the formation of germinal centers. Unlike steady-state Apoe -deficientmice, abrupt loss of APOE induced rapid production of antibodies recognizing rheumatoid disease autoantigens. Genetic ablation of the germinal center reduced both autoimmunity and atherosclerosis, indicating that the immune response that follows loss of APOE is independent of atherosclerosis but nevertheless promotes plaque development. Our findings suggest that immune activation in response to hyperlipidemia could contribute to a wide range of inflammatory autoimmune diseases, including atherosclerosis. © 2018 American Heart Association, Inc.

Autoimmune gastritis.

PubMed

Kulnigg-Dabsch, Stefanie

2016-10-01

Autoimmune gastritis is a chronic inflammatory disease with destruction of parietal cells of the corpus and fundus of the stomach. The known consequence is vitamin B12 deficiency and, consequently, pernicious anemia. However, loss of parietal cells reduces secretion of gastric acid which is also required for absorption of inorganic iron; thus, iron deficiency is commonly found in patients with autoimmune gastritis. This usually precedes vitamin B12 deficiency and is found mainly in young women. Patients with chronic iron deficiency, especially those refractory to oral iron therapy, should therefore be evaluated for the presence of autoimmune gastritis.

Pain in autoimmune disorders.

PubMed

Mifflin, Katherine A; Kerr, Bradley J

2017-06-01

Most autoimmune diseases are associated with pathological pain development. Autoimmune diseases with pathological pain include complex regional pain syndrome, rheumatoid arthritis, and Guillian-Barré syndrome to name a few. The present Review explores research linking the immune system to the development of pathological pain in autoimmune diseases. Pathological pain has been linked to T-cell activation and the release of cytokines from activated microglia in the dorsal horn of the spinal cord. New research on the role of autoantibodies in autoimmunity has generated insights into potential mechanisms of pain associated with autoimmune disease. Autoantibodies may act through various mechanisms in autoimmune disorders. These include the alteration of neuronal excitability via specific antigens such as the voltage-gated potassium channel complexes or by mediating bone destruction in rheumatoid arthritis. Although more research must be done to understand better the role of autoantibodies in autoimmune disease related pain, this may be a promising area of research for new analgesic therapeutic targets. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

Organ specificity in autoimmune diseases: thyroid and islet autoimmunity in alopecia areata.

PubMed

Noso, Shinsuke; Park, Choongyong; Babaya, Naru; Hiromine, Yoshihisa; Harada, Takeshi; Ito, Hiroyuki; Taketomo, Yasunori; Kanto, Kousei; Oiso, Naoki; Kawada, Akira; Suzuki, Tamio; Kawabata, Yumiko; Ikegami, Hiroshi

2015-05-01

Multiple autoimmune diseases, such as autoimmunity against the thyroid gland and pancreatic islets, are often observed in a single patient. Although alopecia areata (AA) is one of the most frequent organ-specific autoimmune diseases, the association of AA with other autoimmune diseases and the genetic basis of the association remain to be analyzed. The aim of this study was to clarify the similarities and differences in HLA and clinical characteristics of thyroid and islet autoimmunity in patients with AA. A total of 126 patients with AA were newly recruited. Anti-islet and antithyroid autoantibodies were tested, and genotypes of HLA genes were determined. Among the autoimmune diseases associated with AA, autoimmune thyroid disease was most frequent (10.0%), followed by vitiligo (2.7%) and rheumatoid arthritis (0.9%) but not type 1 diabetes (0.0%). The prevalence of thyroid-related autoantibodies in patients with AA was significantly higher than that in controls (TSH receptor antibody [TRAb]: 42.7% vs 1.2%, P = 1.6 × 10(-46); thyroid peroxidase antibody: 29.1% vs 11.6%; P = 1.7 × 10(-6)), whereas the prevalence of islet-related autoantibodies was comparable between patients with AA and control subjects. The frequency of DRB1*15:01-DQB1*06:02, a protective haplotype for type 1 diabetes, was significantly higher in TRAb-positive (12.8%, P = .0028, corrected P value [Pc] = .02) but not TRAb-negative (7.1%, not significant) patients with AA than in control subjects (4.5%). The frequency of DRB1*04:05-DQB1*04:01, a susceptible haplotype for type 1 diabetes, was significantly lower in patients with AA (TRAb-positive: 8.5%; TRAb-negative: 11.9%) than in those with type 1 diabetes (29.5%, Pc < .0003 and Pc < .0008, respectively). AA was associated with thyroid autoimmunity but not islet autoimmunity, which correlated with class II HLA haplotypes susceptible or resistant to each autoimmune disease.

Antigenic analysis of Campylobacter species and an intracellular Campylobacter-like organism associated with porcine proliferative enteropathies.

PubMed Central

McOrist, S; Boid, R; Lawson, G H

1989-01-01

Whole-cell and outer membrane preparations of Campylobacter mucosalis, C. hyointestinalis, C. jejuni, and C. coli isolated from porcine intestines were compared with preparations of intracellular Campylobacter-like organisms extracted directly from the lesions of pigs with proliferative enteropathy. By gradient polyacrylamide gel electrophoresis, outer membrane and total protein profiles of C. mucosalis, C. hyointestinalis, C. jejuni, and C. coli were significantly different from each other and from those of the Campylobacter-like organisms. Immunoblotting of these preparations with rabbit antisera or monoclonal antibodies prepared against the intracellular Campylobacter-like organisms showed strong reactions only with a 25,000- to 27,000-molecular-weight component of preparations of the intracellular organisms. Antisera to cultivable Campylobacter species isolates did not react with preparations of intracellular organisms. Isoelectric focusing of sonicated preparations showed protein profile differences and an immune-reactive component in the intracellular organisms with a pI of 4.5. This study suggests that the intracellular Campylobacter-like organism associated with proliferative enteropathy may be a novel bacterium with significant antigenic differences from the Campylobacter species previously associated with the disease. Images PMID:2917794

Haralampos M. Moutsopoulos: a lifetime in autoimmunity.

PubMed

Youinou, Pierre

2010-11-01

Three years ago, the Journal of Autoimmunity and Autoimmunity Reviews launched a series of special issues devoted to the contributions of outstanding scholars in autoimmunology. The special issues are devoted not only to recognize achievements, but also to include a series of dedicated papers that reflect the scholar's work, but also are cutting-edge research and reviews in immunology. This special issue is devoted to Haralampos M. Moutsopoulos of the National University of Athens. His contributions to patient care, teaching, and original research are legion. The papers that are included reflect not only a wide range of scholarship in autoimmunology, but importantly are written by his colleagues and friends, and by former students. They encompass original scholarship in Sjögren's syndrome, but also in a number of effector pathways in both adult and pediatric autoimmunology. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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...

Autoimmunity in the pathogenesis and treatment of keratoconjunctivitis sicca.

PubMed

Liu, Katy C; Huynh, Kyle; Grubbs, Joseph; Davis, Richard M

2014-01-01

Dry eye is a chronic corneal disease that impacts the quality of life of many older adults. Keratoconjunctivitis sicca (KCS), a form of aqueous-deficient dry eye, is frequently associated with Sjögren's syndrome and mechanisms of autoimmunity. For KCS and other forms of dry eye, current treatments are limited, with many medications providing only symptomatic relief rather than targeting the pathophysiology of disease. Here, we review proposed mechanisms in the pathogenesis of autoimmune-based KCS: genetic susceptibility and disruptions in antigen recognition, immune response, and immune regulation. By understanding the mechanisms of immune dysfunction through basic science and translational research, potential drug targets can be identified. Finally, we discuss current dry eye therapies as well as promising new treatment options and drug therapy targets.

Fibrinogen deficiency suppresses the development of early and delayed radiation enteropathy

PubMed Central

Wang, Junru; Pathak, Rupak; Garg, Sarita; Hauer-Jensen, Martin

2017-01-01

AIM To determine the mechanistic role of fibrinogen, a key regulator of inflammation and fibrosis, in early and delayed radiation enteropathy. METHODS Fibrinogen wild-type (Fib+/+), fibrinogen heterozygous (Fib+/-), and fibrinogen knockout (Fib-/-) mice were exposed to localized intestinal irradiation and assessed for early and delayed structural changes in the intestinal tissue. A 5-cm segment of ileum of mice was exteriorized and exposed to 18.5 Gy of x-irradiation. Intestinal tissue injury was assessed by quantitative histology, morphometry, and immunohistochemistry at 2 wk and 26 wk after radiation. Plasma fibrinogen level was measured by enzyme-linked immunosorbent assay. RESULTS There was no difference between sham-irradiated Fib+/+ and Fib+/- mice in terms of fibrinogen concentration in plasma and intestinal tissue, intestinal histology, morphometry, intestinal smooth muscle cell proliferation, and neutrophil infiltration. Therefore, Fib+/- mice were used as littermate controls. Unlike sham-irradiated Fib+/+ and Fib+/- mice, no fibrinogen was detected in the plasma and intestinal tissue of sham-irradiated Fib-/- mice. Moreover, fibrinogen level was not elevated after irradiation in the intestinal tissue of Fib-/- mice, while significant increase in intestinal fibrinogen level was noticed in irradiated Fib+/+ and Fib+/- mice. Importantly, irradiated Fib-/- mice exhibited substantially less overall intestinal structural injury (RIS, P = 0.000002), intestinal wall thickness (P = 0.003), intestinal serosal thickness (P = 0.009), collagen deposition (P = 0.01), TGF-β immunoreactivity (P = 0.03), intestinal smooth muscle proliferation (P = 0.046), neutrophil infiltration (P = 0.01), and intestinal mucosal injury (P = 0.0003), compared to irradiated Fib+/+ and Fib+/- mice at both 2 wk and 26 wk. CONCLUSION These data demonstrate that fibrinogen deficiency directly attenuates development of early and delayed radiation enteropathy. Fibrinogen could be a novel target

Prolactin and Autoimmunity

PubMed Central

Borba, Vânia Vieira; Zandman-Goddard, Gisele; Shoenfeld, Yehuda

2018-01-01

The great asymmetry of autoimmune diseases between genders represents one of the most enigmatic observations among the mosaic of autoimmunity. Sex hormones are believed to play a crucial role on this dimorphism. The higher prevalence of autoimmunity among women at childbearing ages, disease onset/relapses during pregnancy, and post-partum are some of the arguments that support this hypothesis. Certainly, motherhood represents one of the most remarkable challenges for the immune system, which not only has to allow for the conceptus, but also has to deal with complex endocrine alterations. Hormonal homeostasis is known to exert a crucial influence in achieving a competent and healthy immune system. Prolactin (PRL) has a bioactive function acting as a hormone and a cytokine. It interferes with immune system modulation, mainly inhibiting the negative selection of autoreactive B lymphocytes. Likewise, hyperprolactinemia has been described in relation to the pathogenesis and activity of several autoimmune disorders. Dopamine is an effective inhibitor of PRL secretion due to either a direct influence on the hypophysis or stimulation of postsynaptic dopamine receptors in the hypothalamus, arousing the release of the PRL inhibitory factor. Hence, dopamine agonists have proven to offer clinical benefits among autoimmune patients and represent a promising therapy to be explored. In this review, we attempt to provide a critical overview of the link between PRL, autoimmune diseases, and motherhood. PMID:29483903

Prolactin and Autoimmunity.

PubMed

Borba, Vânia Vieira; Zandman-Goddard, Gisele; Shoenfeld, Yehuda

2018-01-01

The great asymmetry of autoimmune diseases between genders represents one of the most enigmatic observations among the mosaic of autoimmunity. Sex hormones are believed to play a crucial role on this dimorphism. The higher prevalence of autoimmunity among women at childbearing ages, disease onset/relapses during pregnancy, and post-partum are some of the arguments that support this hypothesis. Certainly, motherhood represents one of the most remarkable challenges for the immune system, which not only has to allow for the conceptus, but also has to deal with complex endocrine alterations. Hormonal homeostasis is known to exert a crucial influence in achieving a competent and healthy immune system. Prolactin (PRL) has a bioactive function acting as a hormone and a cytokine. It interferes with immune system modulation, mainly inhibiting the negative selection of autoreactive B lymphocytes. Likewise, hyperprolactinemia has been described in relation to the pathogenesis and activity of several autoimmune disorders. Dopamine is an effective inhibitor of PRL secretion due to either a direct influence on the hypophysis or stimulation of postsynaptic dopamine receptors in the hypothalamus, arousing the release of the PRL inhibitory factor. Hence, dopamine agonists have proven to offer clinical benefits among autoimmune patients and represent a promising therapy to be explored. In this review, we attempt to provide a critical overview of the link between PRL, autoimmune diseases, and motherhood.

Eosinophils in Autoimmune Diseases

PubMed Central

Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

2017-01-01

Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

[Non-autoimmune thyroiditis].

PubMed

Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D

2014-01-01

The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

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

PubMed

Selmi, Carlo

2014-08-01

Our understanding of the pathogenic mechanisms and possible treatments of autoimmune diseases has significantly increased over the past decade. Nonetheless, numerous major issues remain open and such issues span from epidemiology to clinimetrics and from the role of infectious agents to the search for accurate biomarkers in paradigmatic conditions such as systemic lupus erythematosus, rheumatoid arthritis, and spondyloarthropathies. In the case of cardiovascular comorbidities of autoimmune diseases or, more generally, the pathogenesis of atherosclerosis, fascinating evidence points to a central role of autoimmunity and metabolic dysfunctions and a possible role of therapies targeting inflammation to ameliorate both conditions. Basic science and translational medicine contribute to identify common mechanisms that underlie different autoimmune diseases, as in the case of tumor necrosis factor alpha, and more recently vitamin D, autoantibodies, T and B regulatory cells, and microRNA. Finally, new therapies are expected to significantly change our approach to autoimmune diseases, as represented by the recent FDA approval of the first oral JAK inhibitor. The present article moves from the major topics that were discussed at the 2013 Asian Congress of Autoimmunity in Hong Kong to illustrate the most recent data from leading journals in autoimmunity and immunology. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed

Yang, Jianying; Chandrasekharappa, Settara C; Vilboux, Thierry; Smith, Ann C M; Peterson, Erik J

2014-08-01

Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena.

Transnodal lymphangiography and post-CT for protein-losing enteropathy in Noonan syndrome.

PubMed

Matsumoto, Tomohiro; Kudo, Takahiro; Endo, Jun; Hashida, Kazunobu; Tachibana, Nao; Murakoshi, Takatsugu; Hasebe, Terumitsu

2015-01-01

Noonan syndrome, which is a multiple congenital disorder, may be associated with lymphatic abnormalities. Protein-losing enteropathy (PLE) developing in Noonan syndrome is rare. We performed transnodal lymphangiography by directly accessing bilateral inguinal nodes under ultrasound guidance in a 17-year-old female with PLE developing in Noonan syndrome to assess detailed anatomical findings regarding lymphatic vessels. There have been no reports on transnodal lymphangiography for Noonan syndrome. Post-lymphangiographic CT images revealed multiple lymphatic abnormalities and lipiodol extravasation into the duodenum and the proximal jejunum. Transnodal lymphangiography was easy and safe for PLE developing in Noonan syndrome, and post-lymphangiographic CT provided invaluable information.

Autoimmune progesterone dermatitis.

PubMed

Detrixhe, A; Nikkels, A F; Dezfoulian, B

2017-11-01

Autoimmune progesterone dermatitis (APD) is an exceptional condition affecting young women of childbearing age with a high prevalence during the third decade of life. The diagnosis should be confirmed using an intradermal skin test to progesterone, during the follicular phase of the menstrual cycle. APD represents an early manifestation of autoimmune disease. A case of APD is presented who after curative treatment did not develop other autoimmune diseases during a 6-year follow-up. Dermatologists, gynecologists and obstetricians should be aware of this rare but highly invalidating entity.

Autoimmunity in the Pathogenesis and Treatment of Keratoconjunctivitis Sicca

PubMed Central

Liu, Katy C.; Huynh, Kyle; Grubbs, Joseph; Davis, Richard M.

2014-01-01

Dry eye is a chronic corneal disease that impacts the quality of life of many older adults. keratoconjunctivitis sicca (KCS), a form of aqueous-deficient dry eye, is frequently associated with Sjögren’s syndrome and mechanisms of autoimmunity. For KCS and other forms of dry eye, current treatments are limited, with many medications providing only symptomatic relief rather than targeting the pathophysiology of disease. Here, we review proposed mechanisms in the pathogenesis of autoimmune-based KCS: genetic susceptibility and disruptions in antigen recognition, immune response, and immune regulation. By understanding the mechanisms of immune dysfunction through basic science and translational research, potential drug targets can be identified. Finally, we discuss current dry eye therapies as well as promising new treatment options and drug therapy targets. PMID:24395332

sirt1-null mice develop an autoimmune-like condition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sequeira, Jedon; Boily, Gino; Bazinet, Stephanie

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 consistentmore » with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease.« less

Determining optimal therapy of dogs with chronic enteropathy by measurement of serum citrulline

PubMed Central

Gerou‐Ferriani, Magda; Allen, Rhiannon; Noble, Peter‐John M.; German, Alexander J.; Caldin, Marco

2018-01-01

Background Serum concentration of citrulline is a useful biomarker in human intestinal disease and indicates globally reduced enterocyte mass and absorptive function in various disease states. Objectives To determine whether serum citrulline concentration is a biomarker in chronic enteropathy (CE) in dogs, to provide useful information regarding optimal treatment or to predict outcome. Animals Seventy‐four dogs with CE and 83 breed‐ and age‐matched hospital controls with no clinical signs of intestinal disease. Methods Retrospective study. Outcome was determined and dogs were categorized by response to treatment as having food‐responsive enteropathy (FRE), antibiotic‐responsive diarrhea (ARD), or idiopathic inflammatory bowel disease (IBD). Disease severity was quantified by the CIBDAI scoring index. Results Serum citrulline concentration did not differ between dogs with CE (median, 8.4 µg/mL, 5th‐95th percentile 2.0‐19.6) and controls (median, 8.1 µg/mL, 5th‐95th percentile 2.2‐19.7, P = .91). Serum citrulline concentration was similar between dogs with FRE (median, 9.1 µg/mL, 5th‐95th percentile 2.0‐18.9), ARD (median, 13.0 µg/mL, 5th‐95th percentile 1.6‐19.2), IBD (median, 8.4 µg/mL, 5th‐95th percentile 2.1‐21.0; P = .91). Serum citrulline did not correlate to CIBDAI or to serum albumin concentration. Conclusions and Clinical Importance In our study, serum citrulline concentration was not associated with efficacy of treatment or outcome in dogs with CE. PMID:29663515

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

PubMed

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

2015-02-25

To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mucosal immune/barrier function, we purified bacterial strains targeted by immunoglobulin A (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. Copyright © 2015, American Association for the Advancement of Science.

[Zinc and chronic enteropathies].

PubMed

Giorgi, P L; Catassi, C; Guerrieri, A

1984-01-01

In recent years the nutritional importance of zinc has been well established; its deficiency and its symptoms have also been recognized in humans. Furthermore, Acrodermatitis Enteropathica has been isolated, a rare but severe disease, of which skin lesions, chronic diarrhoea and recurring infections are the main symptoms. The disease is related to the malfunctioning of intestinal absorption of zinc and can be treated by administering pharmacological doses of zinc orally. Good dietary sources of zinc are meat, fish and, to a less extent, human milk. The amount of zinc absorbed in the small intestine is influenced by other nutrients: some compounds inhibit this process (dietary fiber, phytate) while others (picolinic acid, citric acid), referred to as Zn-binding ligands (ZnBL) facilitate it. Citric acid is thought to be the ligand which accounts for the high level of bioavailability of zinc in human milk. zinc absorption occurs throughout the small intestine, not only in the prossimal tract (duodenum and jejunum) but also in the distal tract (ileum). Diarrhoea is one of the clinical manifestations of zinc deficiency, thus many illnesses distinguished by chronic diarrhoea entail a bad absorption of zinc. In fact, in some cases of chronic enteropathies in infants, like coeliac disease and seldom cystic fibrosis, a deficiency of zinc has been isolated. Some of the symptoms of Crohn's disease, like retarded growth and hypogonadism, have been related to hypozinchemia which is present in this illness. Finally, it is possible that some of the dietary treatments frequently used for persistent post-enteritis diarrhoea (i.e. cow's milk exclusion, abuse and misuse of dietary fiber like carrot and carub powder, use of soy formula) can constitute a scarce supply of zinc and therefore could promote the persistency of diarrhoea itself.

Vaccines, adjuvants and autoimmunity.

PubMed

Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

2015-10-01

Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Somatic PTPN11 Mutation in a Child With Neuroblastoma and Protein Losing Enteropathy.

PubMed

Obasaju, Patience; Brondon, Jennifer; Mir, Sabina; Fordham, Lynn A; Lee, Sang; Blatt, Julie

2018-05-01

Neuroblastoma and protein losing enteropathy (PLE) are diagnoses commonly seen by oncologists and gastroenterologists, respectively. The concurrence of these 2 entities is rare, and not well explained. We describe the sixth case of PLE in a child with neuroblastoma, and the first for which genetic information is available. Tumor DNA had a mutation in the PTPN11 gene, which has been described in neuroblastoma, and in Noonan syndrome-a diagnosis in which neuroblastoma and PLE independently have been reported. Constitutional DNA was normal. Genetic studies in future patients will be needed to support the link between neuroblastoma and PLE.

Autoimmune liver serology: current diagnostic and clinical challenges.

PubMed

Bogdanos, Dimitrios-P; Invernizzi, Pietro; Mackay, Ian-R; Vergani, Diego

2008-06-07

Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1). SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and non-specific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with) traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents, (2) diagnostic service laboratories that fulfill clinicians' requirements, and (3) the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context.

Autoimmune liver serology: Current diagnostic and clinical challenges

PubMed Central

Bogdanos, Dimitrios P; Invernizzi, Pietro; Mackay, Ian R; Vergani, Diego

2008-01-01

Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1). SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and non-specific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with) traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents, (2) diagnostic service laboratories that fulfill clinicians’ requirements, and (3) the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context. PMID:18528935

[Protein-losing enteropathy due to intestinal lymphangiectasis: a rare disease. Report of two cases].

PubMed

Sommaruga, Horacio; Santarcángelo, Salomé Catalina; Quintana, Carlos; Navacchia, Daniel

2015-03-01

Congenital intestinal lymphangiectasis (LIP) is a protein-losing enteropathy that appears sporadically in children. It begins with edema due to hypoproteinemia and hypoalbuminemia, and in some cases with ascites, immunodeficience and hypocalcemic tetania. The purpose of this report is to present two patients with LIP which appeared during the first year of life. The diagnosis was certificated by upper gastrointestinal videoendoscopy and histological findings. Both patients were treated with a new formula containing mean chain triglycerides with an adequate response, not obtained before with a common semielemental formula.

Latent autoimmune diabetes in adults is perched between type 1 and type 2: evidence from adults in one region of Spain.

PubMed

Mollo, Angels; Hernandez, Marta; Marsal, Josep R; Esquerda, Aureli; Rius, Ferran; Blanco-Vaca, Francisco; Verdaguer, Joan; Pozzilli, Paolo; de Leiva, Alberto; Mauricio, Didac

2013-09-01

The aim of this study was to characterize the clinical characteristics and insulin secretion in adults with latent autoimmune diabetes in adults (LADA). We also compared these characteristics in subjects with antibody-negative type 2 diabetes (T2DM) or adult-onset type 1 diabetes (T1DM) to subjects with LADA. In this cross-sectional study, 82 patients with LADA, 78 with T1DM and 485 with T2DM were studied. Clinical and metabolic data, in particular those that related to metabolic syndrome, fasting C-peptide and islet-cell autoantibodies [glutamic acid decarboxylase (GADAb) and IA2 (IA2Ab)] were measured. The frequency of metabolic syndrome in patients with LADA (37.3%) was higher than in those with T1DM (15.5%; p = 0.005) and lower than in patients with T2DM (67.2%; p < 0.001). During the first 36 months of the disease, the C-peptide concentration in LADA patients was higher than in subjects with T1DM but was lower than in T2DM patients (p < 0.01 for comparisons). Glycemic control in LADA patients (HbA1c 8.1%) was worse than in patients with T2DM (HbA1c 7.6%; p =0.007). An inverse association between GADAb titers and C-peptide concentrations was found in subjects with LADA (p < 0.001). Finally, LADA patients rapidly progressed to insulin treatment. As in other European populations, patients with LADA in Spain have a distinct metabolic profile compared with patients with T1DM or T2DM. LADA is also associated with higher impairment of beta-cell function and has worse glycemic control than in T2DM. Beta cell function is related to GADAb titers in patients with LADA. Copyright © 2013 John Wiley & Sons, Ltd.

Autoimmune Alternating Hypo- and Hyperthyroidism in Children

PubMed Central

Mathew, Revi P.; Moore, Daniel J.

2013-01-01

Two children presented with autoimmune alternating hypo- and hyperthyroidism related to the presence of blocking and stimulating thyroid antibodies. It was difficult to control their thyroid function adequately with an appropriate single drug regimen, and both children underwent total thyroidectomy with subsequent stable management with levothyroxine replacement therapy postsurgically. Although this phenomenon is well described in adults, this report is the first of such occurrence in children. The possible mechanism for the variation in the type of clinical presentation and options for management are discussed. PMID:21700620

Sirolimus for Autoimmune Disease of Blood Cells

ClinicalTrials.gov

2017-11-02

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

[Microbiota and autoimmunity].

PubMed

Miyake, Sachiko

2014-01-01

The microbiota plays a fundamental role in the development and the maintenance of the host immune system. Since microbiota is important in the induction and the expansion of Th17 cells and regulatory T cells, growing evidence supports that microbiome affect the induction and the disease course of autoimmune disorders. In this review, we describe the recent studies on the involvement of microbes in animal models of autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS) using germ-free conditions, antibiotics treatment and gnotobiotic mice. Furthermore, we introduce the studies on analysis of microbiota in human autoimmune diseases including RA and MS.

Intestinal lymphangiectasia in a patient with infantile systemic hyalinosis syndrome: a rare cause of protein-losing enteropathy.

PubMed

Alreheili, Khalid; AlMehaidib, Ali; Alsaleem, Khalid; Banemi, Mohammad; Aldekhail, Wajeeh; Al-Mayouf, Sulaiman M

2012-01-01

Infantile systemic hyalinosis (ISH) is a rare autosomal recessive disease. Typically, ISH patients present with progressive painful joint contractures, intractable diarrhea, hyperpigmented skin lesions, and peri-anal fleshy nodules. We report a case of a 19-month-old male child with atypical ISH presentation. His main clinical finding was protein-losing enteropathy due to intestinal lymphangectasia. This report is intended to enhance awareness about the gastrointestinal tract presentation of ISH.

[The pathogenesis and regulation of autoimmunity].

PubMed

Miyake, Sachiko

2008-06-01

The pathogenesis of autoimmunity has been studied extensively using animal models and genome-wide genetic analysis. Moreover, recent advance in the therapy for the autoimmune diseases using molecular-targeted drugs has provided us a lot of information in the pathogenesis of human autoimmune diseases. In this review, we overviewed the recent progress in the study of autoimmunity including central tolerance, regulatory cells and cytokines. Finally, we discuss the relationship of innate immunity and adoptive immunity in the context of autoimmunity.

Autoimmune phenomena following prostatectomy.

PubMed

Tweezer-Zaks, Nurit; Marai, Ibrahim; Livneh, Avi; Bank, Ilan; Langevitz, Pnina

2005-09-01

Benign prostatic hypertrophy is the most common benign tumor in males, resulting in prostatectomy in 20-30% of men who live to the age of 80. There are no data on the association of prostatectomy with autoimmune phenomena in the English-language medical literature. To report our experience with three patients who developed autoimmune disease following prostatectomy. Three patients presented awith autoimmune phenomenon soon after a prostectomy for BPH or prostatic carcinoma: one had clinically diagnosed temporal arteritis, one had leukocytoclastic vasculitis, and the third patient developed sensory Guillian-Barré syndrome following prostatectomy. In view of the temporal association between the removal of the prostate gland andthe autoimmune process, combined with previously known immunohistologic features of BPH, a cause-effect relationship probably exists.

Autoimmune gastritis: Pathologist's viewpoint.

PubMed

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

2015-11-14

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.

Is vaginal mesh a stimulus of autoimmune disease?

PubMed

Chughtai, Bilal; Sedrakyan, Art; Mao, Jialin; Eilber, Karyn S; Anger, Jennifer T; Clemens, J Quentin

2017-05-01

Polypropylene mesh has been used as a means of reinforcing weak tissues in women with pelvic organ prolapse and stress urinary incontinence. We sought to investigate a potential link between the development of systemic/autoimmune disorders and synthetic polypropylene mesh repairs. New York State Department of Health Statewide Planning and Research Cooperative System data were utilized to conduct this retrospective cohort study. Adult women undergoing surgery for pelvic organ prolapse with vaginally implanted mesh from January 2008 through December 2009 in inpatient and ambulatory surgery settings in New York State were identified. Two separate control cohorts were created to compare outcomes, including a screening colonoscopy cohort and a vaginal hysterectomy cohort for benign gynecologic conditions (without pelvic organ prolapse repair or sling). Patients in the mesh cohort were individually matched to the control cohorts based on demographics, comorbidities, and procedure date. The development of systemic/autoimmune disease was determined before and after matching for 1-year, 2-year, 3-year, and entire follow-up (up to 6 years until December 2014) and differences between groups were evaluated. A total of 2102 patients underwent mesh-based pelvic organ prolapse surgery from January 2008 through December 2009. In the control cohorts, 37,298 patients underwent colonoscopy and 7338 underwent vaginal hysterectomy. When patients were matched based on demographics, comorbidities, and procedure time, mesh-based surgery was not associated with an increased risk of developing autoimmune disease at any of the evaluated time periods. Mesh-based vaginal surgery was not associated with the development of systemic/autoimmune diseases. These data refute claims against mesh as a cause of systemic disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Cryptogenia multifocal ulcerous stenosing enteritis: an entity on its own as a cause of abdominal pain, iron deficiency anemia and protein-losing enteropathy.

PubMed

Guisado Vasco, P; Fraile Rodríguez, G

2014-01-01

We studied a patient with edema secondary to protein losing enteropathy, and recurrent bouts of bloating and abdominal pain secondary to intestinal subocclusion episodes. After the clinical study, the patient was diagnosed of cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), that is a rare disease, probably caused by mutations in the gene PLA2G4A, and characterized by multiple short stenosis of the small bowel with superficial ulcers, which do not exceed the submucosa layer. Inflammatory bowel disease (Chron's disease), intestinal tuberculosis and intestinal ulcers secondary to non-steroidal anti-inflammatory drugs are the main differential diagnosis. To sum up, physicians should included CMUSE in the differential diagnosis of recurrent abdominal pain, iron deficiency anaemia, occult intestinal bleeding, edema and protein losing enteropathy. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Novel pebbles in the mosaic of autoimmunity.

PubMed

Perricone, Carlo; Agmon-Levin, Nancy; Shoenfeld, Yehuda

2013-04-04

Almost 25 years ago, the concept of the 'mosaic of autoimmunity' was introduced to the scientific community, and since then this concept has continuously evolved, with new pebbles being added regularly. We are now looking at an era in which the players of autoimmunity have changed names and roles. In this issue of BMC Medicine, several aspects of autoimmunity have been addressed, suggesting that we are now at the forefront of autoimmunity science. Within the environmental factors generating autoimmunity are now included unsuspected molecules such as vitamin D and aluminum. Some adjuvants such as aluminum are recognized as causal factors in the development of the autoimmune response. An entirely new syndrome, the autoimmune/inflammatory syndrome induced by adjuvants (ASIA), has been recently described. This is the new wind blowing within the branches of autoimmunity, adding knowledge to physicians for helping patients with autoimmune disease.

Development of Gluten-Free Cakes

USDA-ARS?s Scientific Manuscript database

Celiac (coeliac) disease, also known as celiac sprue and gluten–sensitive enteropathy, is one of the most frequent food intolerances in the world. It is an autoimmune disorder prevalent in 1:133 of the US population and 1:266 of the population worldwide. Celiac disease is characterized by the inflam...

Multiplex autoantibody detection for autoimmune liver diseases and autoimmune gastritis.

PubMed

Vanderlocht, Joris; van der Cruys, Mart; Stals, Frans; Bakker-Jonges, Liesbeth; Damoiseaux, Jan

2017-09-01

Autoantibody detection for autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and autoimmune gastritis (AIG) is traditionally performed by IIF on a combination of tissues. Multiplex line/dot blots (LIA/DIA) offer multiple advantages, i.e. automation, objective reading, no interfering reactivities, no coincidental findings. In the current study we evaluated automated DIA (D-Tek) for detecting autoantibodies related to autoimmune diseases of the gastrointestinal tract. We tested samples of the Dutch EQC program and compared the results with the consensus of the participating labs. For the autoimmune liver diseases and AIG, respectively, 64 and 36 samples were tested. For anti-mitochondrial and anti-smooth muscle antibodies a concordance rate of 97% and 88% was observed, respectively. The concordance rate for anti-parietal cell antibodies was 92% when samples without EQC consensus (n=15) were excluded. For antibodies against intrinsic factor a concordance of 96% was observed. For all these antibodies discrepancies were identified that relate to the different test characteristics and the preponderance of IIF utilizing labs in the EQC program. In conclusion, we observed good agreement of the tested DIA blots with the consensus results of the Dutch EQC program. Taken together with the logistic advantages these blots are a good alternative for autoantibody detection in the respective diseases. A large prospective multicenter study is warranted to position these novel tests further in the whole spectrum of assays for the detection of these antibodies in a routine autoimmune laboratory. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Autoimmune diseases and vaccinations.

PubMed

Vial, Thierry; Descotes, Jacques

2004-01-01

The potential association between vaccination and autoimmune diseases has been largely questioned in the past few years, but this assumption has mostly been based on case reports. The available evidence derived from several negative epidemiological studies is reassuring and at least indicates that vaccines are not a major cause of autoimmune diseases. However, there are still uncertainties as to whether a susceptible subpopulation may be at a higher risk of developing an autoimmune disease without causing an overall increase in the disease incidence. Based on selected examples, this review highlights the difficulties in assessing this issue. We suggest that a potential link between vaccines and autoimmune diseases cannot be definitely ruled out and should be carefully explored during the development of new candidate vaccines. Copyright John Libbey Eurotext 2003.

Autoantibodies in Autoimmune Hepatitis.

PubMed

Muratori, Luigi; Deleonardi, Gaia; Lalanne, Claudine; Barbato, Erica; Tovoli, Alessandra; Libra, Alessia; Lenzi, Marco; Cassani, Fabio; Muratori, Paolo

2015-01-01

The detection of diagnostic autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-liver/kidney microsomal type 1 (anti-LKM1), anti-liver cytosol type 1 (anti-LC1) and anti-soluble liver antigen (anti-SLA) is historically associated with the diagnosis of autoimmune hepatitis. When autoimmune hepatitis is suspected, the detection of one or any combination of diagnostic autoantibodies, by indirect immunofluorescence or immuno-enzymatic techniques with recombinant antigens, is a pivotal step to reach a diagnostic score of probable or definite autoimmune hepatitis. Diagnostic autoantibodies (ANA, SMA, anti-LKM1, anti-LC1, anti-SLA) are a cornerstone in the diagnosis of autoimmune hepatitis. Other ancillary autoantibodies, associated with peculiar clinical correlations, appear to be assay-dependent and institution-specific, and validation studies are needed. © 2015 S. Karger AG, Basel.

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

PubMed Central

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

2001-01-01

OBJECTIVES—To review the autoimmune and rheumatic manifestations of patients with malignancy.
METHODS—A Medline search of all published papers using keywords related to malignancies, autoimmunity, rheumatic diseases, and paraneoplastic syndromes.
RESULTS—Patients with malignant diseases may develop autoimmune phenomena and rheumatic diseases as a result of (a) generation of autoantibodies against various autoantigens, including oncoproteins (P185, 1-myc, c-myc, c-myb), tumour suppression genes (P53), proliferation associated antigens (cyclin A, B1, D1, E; CENP-F; CDK, U3-RNP), onconeural antigens (Hu, Yo, Ri, Tr), cancer/testis antigens (MAGE, GAGE, BAGE, SSX, ESO, SCP, CT7), and rheumatic disease associated antigens (RNP, Sm). The clinical significance of the various autoantibodies is not clear. Anti-oncoprotein and anti-tumour suppression gene antigens are detected before the diagnosis of the cancer or in the early stages of the malignant disease, suggesting a potential diagnostic or prognostic role. Anti-onconeural antibodies are pathogenic and are associated with specific clinical neurological syndromes (anti-Hu syndrome and others). (b) Paraneoplastic syndromes, a wide range of clinical syndromes, including classic autoimmune rheumatic diseases that develop among patients with cancer. (c) Rheumatism after chemotherapy, a clinical entity characterised by the development of musculoskeletal symptoms after combination chemotherapy for malignancy.
CONCLUSION—Autoimmune and rheumatic features are not rare among patients with malignancies. They are the result of various diverse mechanisms and occasionally they may be associated with serious clinical entities.

 PMID:11302861

The autoimmune ecology: an update.

PubMed

Anaya, Juan-Manuel; Restrepo-Jiménez, Paula; Ramírez-Santana, Carolina

2018-07-01

The autoimmune ecology refers to the interactions between individuals and their environment leading to a breakdown in immune tolerance and, therefore, to the development of one or more autoimmune diseases in such an individual. Herein, an update is offered on four specific factors associated with autoimmune diseases, namely, vitamin D, smoking, alcohol and coffee consumption from the perspective of exposome and metabolomics. Smoking is associated with an increased risk for most of the autoimmune diseases. Carbamylation of proteins as well as NETosis have emerged as possible new pathophysiological mechanisms for rheumatoid arthritis. Low-to-moderate alcohol consumption seems to decrease the risk of systemic lupus erythematosus and rheumatoid arthritis, and studies of vitamin have suggested a beneficial effect on these conditions. Coffee intake appears to be a risk factor for type 1 diabetes mellitus and rheumatoid arthritis and a protective factor for multiple sclerosis and primary biliary cholangitis. Recent studies support the previously established positive associations between environmental factors and most of the autoimmune diseases. Nevertheless, further studies from the perspective of metabolomics, proteomics and genomics will help to clarify the effect of environment on autoimmune diseases.

Assessment of virally vectored autoimmunity as a biocontrol strategy for cane toads.

PubMed

Pallister, Jackie A; Halliday, Damien C T; Robinson, Anthony J; Venables, Daryl; Voysey, Rhonda D; Boyle, Donna G; Shanmuganathan, Thayalini; Hardy, Christopher M; Siddon, Nicole A; Hyatt, Alex D

2011-01-25

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. 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. 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.

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

Autoimmune encephalitis update

PubMed Central

Dalmau, Josep; Rosenfeld, Myrna R.

2014-01-01

Cancer-associated immune-mediated disorders of the central nervous system are a heterogeneous group. These disorders include the classic paraneoplastic neurologic disorders and the more recently described autoimmune encephalitis associated with antibodies to neuronal cell-surface or synaptic receptors that occur with and without a cancer association. Autoimmune encephalitis is increasingly recognized as the cause of a variety of neuropsychiatric syndromes that can be severe and prolonged. In contrast to the classic paraneoplastic disorders that are poorly responsive to tumor treatment and immunotherapy, autoimmune encephalitis often responds to these treatments, and patients can have full or marked recoveries. As early treatment speeds recovery, reduces disability, and decreases relapses that can occur in about 20% of cases, it is important that the immune pathogenesis of these disorders is recognized. PMID:24637228

De novo autoimmune hepatitis after liver transplantation.

PubMed

Lohse, Ansgar W; Weiler-Norman, Christina; Burdelski, Martin

2007-10-01

The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development of SLA/LP-autoantibodies is also not described. Therefore, serologically de novo AIH appears to correspond to type 1 AIH. Like classical AIH patients respond promptly to treatment with increased doses of prednisolone and azathioprine, while the calcineurin inhibitors cyclosporine or tacrolimus areof very limited value - which is not surprising, as almost all patients develop de novo AIH while receiving these drugs. Despite the good response to treatment, most patients remain a clinical challenge as complete stable remissions are uncommon and flares, relapses and chronic disease activity can often occur. Pathogenetically this syndrome is intriguing. It is not clear, if the immune response is directed against allo-antigens, neo-antigens in the liver, or self-antigens, possibly shared by donor and host cells. It is very likely that the inflammatory milieu due to alloreactive cells in the transplanted organ contribute to the disease process. Either leading to aberrant antigen presentation, or providing co-stimulatory signals leading to the breaking of self-tolerance. The development of this disease in the presence of treatment with calcineurin

Autoimmune paediatric liver disease

PubMed Central

Mieli-Vergani, Giorgina; Vergani, Diego

2008-01-01

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a

Autoimmune paediatric liver disease.

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego

2008-06-07

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a

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.

Autoimmune encephalitis associated with vitiligo?

PubMed

Haitao, Ren; Huiqin, Liu; Tao, Qu; Xunzhe, Yang; Xiaoqiu, Shao; Wei, Li; Jiewen, Zhang; Liying, Cui; Hongzhi, Guan

2017-09-15

The autoimmune encephalitis can develop with or without an underlying tumor. For tumor-negative autoimmune encephalitis, the causes are still largely unknown. Here we presented three patients with autoimmune encephalitis accompanied with vitiligo. Among them, two patients suffered from anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis and one patient suffered from anti-IgLON5 encephalopathy. All of them received intravenous immunoglobulin and steroids as immunotherapy. The two patients with anti-LGI1 encephalitis recovered and got a good prognosis. For the patient with anti-IgLON5 encephalopathy, he only got a moderate and transient improvement. Based on the above, we speculate that vitiligo may be a clue to an autoimmune cause for encephalitis. Copyright © 2017. Published by Elsevier B.V.

Autoimmunity and the Gut

PubMed Central

Campbell, Andrew W.

2014-01-01

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

Amygdala enlargement and emotional responses in (autoimmune) temporal lobe epilepsy.

PubMed

Holtmann, Olga; Schlossmacher, Insa; Moenig, Constanze; Johnen, Andreas; Rutter, Lisa-Marie; Tenberge, Jan-Gerd; Schiffler, Patrick; Everding, Judith; Golombeck, Kristin S; Strippel, Christine; Dik, Andre; Schwindt, Wolfram; Wiendl, Heinz; Meuth, Sven G; Bruchmann, Maximilian; Melzer, Nico; Straube, Thomas

2018-06-22

Temporal lobe epilepsy with amygdala enlargement (TLE-AE) is increasingly recognized as a distinct adult electroclinical syndrome. However, functional consequences of morphological alterations of the amygdala in TLE-AE are poorly understood. Here, two emotional stimulation designs were employed to investigate subjective emotional rating and skin conductance responses in a sample of treatment-naïve patients with suspected or confirmed autoimmune TLE-AE (n = 12) in comparison to a healthy control group (n = 16). A subgroup of patients completed follow-up measurements after treatment. As compared to healthy controls, patients with suspected or confirmed autoimmune TLE-AE showed markedly attenuated skin conductance responses and arousal ratings, especially pronounced for anxiety-inducing stimuli. The degree of right amygdala enlargement was significantly correlated with the degree of autonomic arousal attenuation. Furthermore, a decline of amygdala enlargement following prompt aggressive immunotherapy in one patient suffering from severe confirmed autoimmune TLE-AE with a very recent clinical onset was accompanied by a significant improvement of autonomic responses. Findings suggest dual impairments of autonomic and cognitive discrimination of stimulus arousal as hallmarks of emotional processing in TLE-AE. Emotional responses might, at least partially, recover after successful treatment, as implied by first single case data.

Isohormonal therapy of endocrine autoimmunity.

PubMed

Schloot, N; Eisenbarth, G S

1995-06-01

For most autoimmune disorders, the site (if any) of chronic immunization required for perpetuation of autoimmunity is unknown. However, one possible site is the target organ itself. If this were the case, feedback regulation of target cell activity might influence autoimmunity. Here, Nanette Schloot and George Eisenbarth review several recent studies suggesting that therapies that inhibit hormonal secretion of target endocrine organs, and/or modulate immunity by therapy with the isohormone, are associated with disease suppression.

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

Rare variants and autoimmune disease.

PubMed

Massey, Jonathan; Eyre, Steve

2014-09-01

The study of rare variants in monogenic forms of autoimmune disease has offered insight into the aetiology of more complex pathologies. Research in complex autoimmune disease initially focused on sequencing candidate genes, with some early successes, notably in uncovering low-frequency variation associated with Type 1 diabetes mellitus. However, other early examples have proved difficult to replicate, and a recent study across six autoimmune diseases, re-sequencing 25 autoimmune disease-associated genes in large sample sizes, failed to find any associated rare variants. The study of rare and low-frequency variation in autoimmune diseases has been made accessible by the inclusion of such variants on custom genotyping arrays (e.g. Immunochip and Exome arrays). Whole-exome sequencing approaches are now also being utilised to uncover the contribution of rare coding variants to disease susceptibility, severity and treatment response. Other sequencing strategies are starting to uncover the role of regulatory rare variation. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

Vaccination in adult patients with auto-immune inflammatory rheumatic diseases: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases.

PubMed

van Assen, S; Elkayam, O; Agmon-Levin, N; Cervera, R; Doran, M F; Dougados, M; Emery, P; Geborek, P; Ioannidis, J P A; Jayne, D R W; Kallenberg, C G M; Müller-Ladner, U; Shoenfeld, Y; Stojanovich, L; Valesini, G; Wulffraat, N M; Bijl, M

2011-04-01

To present the systematic literature review (SLR), which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases (AIIRD). AIIRD, vaccines and immunomodulating drugs, as well as eight key questions were defined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A SLR was performed using MedLine through October 2009 and including data from meta-analyses, systematic reviews, randomized trials, and observational studies, excluding case series with ≤ 5 participants. Articles in English and regarding patients ≥ 16 years of age, were eligible. Several vaccine-preventable infections (VPI) occur more often in AIIRD-patients and most vaccines are efficacious in AIIRD-patients, even when treated with immunomodulating agents, except rituximab. There does not appear to be an increase in vaccination-related harms in vaccinated patients with AIIRD in comparison with unvaccinated patients with AIIRD. However, these studies are underpowered and therefore not conclusive. Based on the current evidence from the literature, recommendations for vaccination in patients with AIIRD were made. However, more research is needed in particular regarding incidence of VPI, harms of vaccination and the influence of (new and established) immunomodulating agents on vaccination efficacy. Copyright © 2011 Elsevier B.V. All rights reserved.

Autoimmune liver disease in children.

PubMed

Mieli-Vergani, G; Vergani, D

2003-03-01

Autoimmune liver disorders are characterised by an inflammatory liver histology, circulating non-organ specific autoantibodies and increased levels of immunoglobulin G (IgG) in the absence of a known aetiology. They respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Liver disorders with a likely autoimmune pathogenesis include autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Two types of AIH are recognised according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA) deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological and histological presentation of ASC is often indistinguishable from that of AIH. In both, there are high IgG, non-organ specific autoantibodies and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalisation of biochemical parameters and decreased inflammatory activity on follow-up liver biopsies. However, the cholangiopathy can progress and there may be an evolution from AIH to ASC over the years, despite treatment. Whether the juvenile autoimmune form of sclerosing cholangitis and AIH are 2 distinct entities, or different aspects of the same condition, remains to be elucidated.

Dietary naringenin supplementation attenuates experimental autoimmune encephalomyelitis by modulating autoimmune inflammatory responses in mice

USDA-ARS?s Scientific Manuscript database

Autoimmune disease is prevalent in humans. Since conventional therapies have limited efficacy and often come with significant side effects, nutrition may provide an alternative and complementary approach to improving the autoimmune disorders. Naringenin, a flavonoid found in citrus fruits, has been ...

Clinical aspects of autoimmune rheumatic diseases.

PubMed

Goldblatt, Fiona; O'Neill, Sean G

2013-08-31

Multisystem autoimmune rheumatic diseases are heterogeneous rare disorders associated with substantial morbidity and mortality. Efforts to create international consensus within the past decade have resulted in the publication of new classification or nomenclature criteria for several autoimmune rheumatic diseases, specifically for systemic lupus erythematosus, Sjögren's syndrome, and the systemic vasculitides. Substantial progress has been made in the formulation of new criteria in systemic sclerosis and idiopathic inflammatory myositis. Although the autoimmune rheumatic diseases share many common features and clinical presentations, differentiation between the diseases is crucial because of important distinctions in clinical course, appropriate drugs, and prognoses. We review some of the dilemmas in the diagnosis of these autoimmune rheumatic diseases, and focus on the importance of new classification criteria, clinical assessment, and interpretation of autoimmune serology. In this era of improvement of mortality rates for patients with autoimmune rheumatic diseases, we pay particular attention to the effect of leading complications, specifically cardiovascular manifestations and cancer, and we update epidemiology and prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

PREVALENCE OF AUTOIMMUNE THYROIDITIS AND THYROID DYSFUNCTION IN HEALTHY ADULT MEXICANS WITH A SLIGHTLY EXCESSIVE IODINE INTAKE.

PubMed

Flores-Rebollar, Armando; Moreno-Castañeda, Lidia; Vega-Servín, Norman S; López-Carrasco, Guadalupe; Ruiz-Juvera, Aída

2015-08-01

the purpose of this study was to evaluate the prevalence of autoimmune thyroiditis and thyroid dysfunction in healthy individuals with no previously known thyroid disease, in an urban area of Mexico City. the study was conducted on volunteers with no known thyroid disease. We recruited 427 subjects among the hospital's medical and administration personnel. All underwent thyroid ultrasound (US) and TSH, free T4 (FT4), total T3 (TT3), thyroid anti-peroxidase (TPOAb) and anti-thyroglobulin (TgAb) antibodies were measured. Hypoechogenicity and thyroid volume were determined by US. Urinary iodine (UI) excretion was also measured. the frequency of autoimmune thyroiditis was 8.4% (36/427) and women were most commonly affected than men (11.6 vs. 4.3% respectively, P = 0.008); when including cases of atrophic thyroid, the frequency increased to 15.7% (67/427). Clinical hypothyroidism was detected in 1.2% (5/427) and it was sub-clinical in 5.6% of individuals. A goiter was present in 5.9% (25/427) of volunteers. Median UI was 267 μg/L, (IQR 161.3 - 482.5). in spite of our study's limitations, the frequency of autoimmune thyroiditis is clearly elevated in the studied population. Further studies are necessary in order to define the prevalence of autoimmune thyroid disease as well as the current iodine nutritional status in our country. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

No association of psoriasis with autoimmune thyroiditis.

PubMed

Vassilatou, E; Papadavid, E; Papastamatakis, P; Alexakos, D; Koumaki, D; Katsimbri, P; Hadjidakis, D; Dimitriadis, G; Rigopoulos, D

2017-01-01

Common autoimmune diseases tend to coexist in the same patients. Few studies have examined the possible association between autoimmune thyroiditis and psoriasis or psoriatic arthritis (PsA), with inconsistent results. To investigate the prevalence of autoimmune thyroiditis in psoriatic patients with or without PsA, living in an iodine-sufficient area. We studied prospectively, 114 psoriatic patients with disease duration of 5-38 years, 30 of them with PsA, and 286 age- and body mass index (BMI)-matched subjects without psoriasis or known thyroid disease or autoimmune disease. A detailed medical history was obtained from all participants and clinical examination and laboratory evaluation was performed. Psoriasis severity was assessed with Psoriasis Area and Severity Index (PASI). Autoimmune thyroiditis was defined by the presence of positive autoantibodies to thyroid peroxidase and/or thyroglobulin. There was no difference in the prevalence of autoimmune thyroiditis between psoriatic patients and controls (20.2% vs. 19.6%). The prevalence of autoimmune thyroiditis in male and female psoriatic patients was similar (9.6% and 10.5% respectively), in contrast to the increased, as expected, prevalence in female vs. male controls (14.7% vs. 4.9%, P < 0.01). Detected cases with hypothyroidism due to autoimmune thyroiditis were similar in psoriatic patients and controls (7.9% and 7.0% respectively). Autoimmune thyroiditis in psoriatic patients was not related with age of psoriasis onset, psoriasis duration, PASI score, PsA and obesity. These data support that psoriatic patients with or without PsA do not have an increased risk for autoimmune thyroiditis. © 2016 European Academy of Dermatology and Venereology.

Coherent Somatic Mutation in Autoimmune Disease

PubMed Central

Ross, Kenneth Andrew

2014-01-01

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

Paraneoplastic autoimmune movement disorders.

PubMed

Lim, Thien Thien

2017-11-01

To provide an overview of paraneoplastic autoimmune disorders presenting with various movement disorders. The spectrum of paraneoplastic autoimmune disorders has been expanding with the discovery of new antibodies against cell surface and intracellular antigens. Many of these paraneoplastic autoimmune disorders manifest as a form of movement disorder. With the discovery of new neuronal antibodies, an increasing number of idiopathic or neurodegenerative movement disorders are now being reclassified as immune-mediated movement disorders. These include anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis which may present with orolingual facial dyskinesia and stereotyped movements, CRMP-5 IgG presenting with chorea, anti-Yo paraneoplastic cerebellar degeneration presenting with ataxia, anti-VGKC complex (Caspr2 antibodies) neuromyotonia, opsoclonus-myoclonus-ataxia syndrome, and muscle rigidity and episodic spasms (amphiphysin, glutamic acid decarboxylase, glycine receptor, GABA(A)-receptor associated protein antibodies) in stiff-person syndrome. Movement disorders may be a presentation for paraneoplastic autoimmune disorders. Recognition of these disorders and their common phenomenology is important because it may lead to the discovery of an occult malignancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reduced Histone H3 Lysine 9 Methylation Contributes to the Pathogenesis of Latent Autoimmune Diabetes in Adults via Regulation of SUV39H2 and KDM4C.

PubMed

Liu, Xi-Yu; Li, Hong

2017-01-01

Aims . Latent autoimmune diabetes in adults (LADA) is an autoimmune disease of which the mechanism is not clear. Emerging evidence suggests that histone methylation contributes to autoimmunity. Methods . Blood CD4 + T lymphocytes from 26 LADA patients and 26 healthy controls were isolated to detect histone H3 lysine 4 and H3 lysine 9 methylation status. Results . Reduced global H3 lysine 9 methylation was observed in LADA patients' CD4 + T lymphocytes, compared to healthy controls ( P < 0.05). H3 lysine 4 methylation was not statistically different. The reduced H3 lysine 9 methylation was associated with GADA titer but not correlated with glycosylated hemoglobin (HbA1c). When the LADA patient group was divided into those with complication and those without, relatively reduced global H3 lysine 9 methylation was observed in LADA patients with complication ( P < 0.05). The expression of histone methyltransferase SUV39H2 for H3 lysine 9 methylation was downregulated in LADA patients, and the expression of histone demethylase KDM4C which made H3 lysine 9 demethylation was upregulated. Conclusion . The reduction of histone H3 lysine 9 methylation which may due to the downregulation of methyltransferase SUV39H2 and the upregulation of demethylase KDM4C was found in CD4 + T lymphocytes of LADA patients.

Syncytial giant-cell hepatitis due to autoimmune hepatitis type II (LKM1+) presenting as subfulminant hepatitis.

PubMed

Ben-Ari, Z; Broida, E; Monselise, Y; Kazatsker, A; Baruch, J; Pappo, O; Skappa, E; Tur-Kaspa, R

2000-03-01

Giant cell hepatitis (GCH) in adults is a rare event. The diagnosis of GCH is based on findings of syncytial giant hepatocytes. It is commonly associated with either viral infection or autoimmune hepatitis type I. A patient with GCH due to autoimmune hepatitis type II (LKM1+) is described, a combination that has not been previously reported. Corticosteroid therapy was effective in decreasing serum liver enzymes; however, the patient deteriorated rapidly and developed subfulminant hepatic failure. Although an emergency orthotopic liver transplantation was performed, the patient died because of reperfusion injury. Interestingly, only a few giant hepatocytes were noted in the explanted liver. This case stresses the association of GCH with autoimmune disorders, the possible immune mechanism involved in the formation of giant cell hepatocytes, and illustrates the rapidly progressive course and unfavorable prognosis that these patients can develop.

Diagnosis and classification of autoimmune orchitis.

PubMed

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

2014-01-01

Autoimmune orchitis is characterized by testis inflammation and the presence of specific antisperm antibodies (ASA). It is classified in two categories. Primary autoimmune orchitis is defined by infertility and asymptomatic orchitis associated with ASA (100%) directed to the basement membrane or seminiferous tubules in infertile men, without any systemic disease and usually asymptomatic. Secondary autoimmune orchitis is characterized by symptomatic orchitis and/or testicular vasculiti`s associated with a systemic autoimmune disease, particularly vasculitis. These patients typically demonstrate testicular pain, erythema and/or swelling. ASA in secondary autoimmune orchitis have been reported in up to 50% of patients, especially in systemic lupus erythematosus patients. The pathogenesis of primary as well as secondary autoimmune orchitis is still unknown. Although the etiology is likely to be multifactorial, testicular inflammation, infection or trauma may induce T cell response with pro-inflammatory cytokine production with a consequent blood-testis-barrier permeability alteration, ASA production and apoptosis of spermatocytes and spermatids. ASA is known to cause immobilization and/or agglutination of spermatozoa, which may block sperm-egg interaction resulting in infertility. Assisted reproduction has been used as an efficient option in primary cases and immunosuppressive therapy for secondary autoimmune orchitis, although there is no double-blind, randomized trial to confirm the efficacy of any treatment regimens for these conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Severe Autoimmune Adverse Events Post Herpes Zoster Vaccine: A Case-Control Study of Adverse Events in a National Database.

PubMed

Lai, Yi Chun; Yew, Yik Weng

2015-07-01

Zoster vaccine is recommended to reduce the incidence of herpes zoster and its complication of postherpetic neuralgia in older adults. However, there have been reports of autoimmune side effects post vaccination. We therefore aim to investigate the possible relationship of severe autoimmune adverse events (arthritis, vasculitis, systemic lupus erythematosus, thrombocytopenia, alopecia, Guillain-Barre syndrome, optic neuritis and multiple sclerosis) post zoster vaccination with a matched case-control study of reported events in the Vaccine Adverse Event Reporting System (VAERS). Our study showed no significantly increased risks of severe autoimmune adverse events, except arthritis and alopecia, after vaccination. Compared to the unexposed, patients with zoster vaccination had 2.2 and 2.7 times the odds of developing arthritis and alopecia, respectively (P<0.001 and P=0.015, respectively). However, almost none of these events was life threatening. Zoster vaccine is, therefore, relatively safe and unlikely to exacerbate or induce autoimmune diseases. Given its benefits and safety but low coverage, dermatologists and primary care physicians should encourage zoster vaccine use in elderly patients, including selected patients with autoimmune diseases.

Association pernicious anemia and autoimmune polyendocrinopathy: a retrospective study.

PubMed

Zulfiqar, A A; Andres, E

2017-01-01

To investigate the association between pernicious anemia and other autoimmune diseases. This retrospective and bicentric study was conducted at Reims and Strasbourg University Hospitals and involved 188 patients with pernicious anemia examined between 2000 and 2010 in order to search for other autoimmune diseases and to evaluate the role of pernicious anemia in autoimmune polyglandular syndrome. A total of 74 patients with a combination of pernicious anemia and other autoimmune diseases were included in the study. Our study revealed the privileged association of pernicious anemia with autoimmune thyroiditis. The association of pernicious anemia and autoimmune thyroiditis are a part of the autoimmune polyglandular syndrome type 3b. We suggest undertaking a systematic clinical examination and laboratory investigations in search of autoimmune thyroiditis in patient(s) with the diagnosis of pernicious anemia. The association of pernicious anemia and autoimmune thyroiditis is frequent and a part of autoimmune polyglandular 3b.

Voltage gated potassium channel antibodies positive autoimmune encephalopathy in a child: A case report and literature review of an under-recognized condition

PubMed Central

Ganesan, Subramanian; Beri, Sushil; Khan, Beri; Hussain, Nahin

2013-01-01

Autoimmune limbic encephalitis (LE) associated with voltage gated potassium channel antibodies (VGKC-Abs) in children is more common than previously thought and is not always paraneoplastic. Non-neoplastic, autoimmune LE associated with VGKC-Abs has been described recently. However, only few case reports in children as the disease is predominantly described in the adult population. It is likely that this type of autoimmune encephalitis is currently under-diagnosed and hence, under-treated, especially in children. We present a 13-year-old previously fit and healthy African girl diagnosed with LE and we reviewed the literature for its current management. PMID:24339586

Curcumin and autoimmune disease.

PubMed

Bright, John J

2007-01-01

The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

Auto-immune hepatitis following delivery.

PubMed

Saini, Vandana; Gupta, Mamta; Mishra, S K

2013-05-01

Auto-immune hepatitis first presenting in the early postpartum period is rare. Immunosuppressive effects of pregnancy result in delayed manifestation of auto-immune hepatitis, and in established cases, the spontaneous improvements are there. Auto-immune hepatitis should be considered in the differential diagnosis of liver dysfunction first presenting in the early postpartum period. A case of postpartum hepatitis of auto-immune aetiology is being presented here. It is disease of unknown aetiology, characterised by inflammation of liver (as evidenced by raised serum transaminases, presence of interface hepatitis on histological examination), hypergammaglobulinaemia (> 1.5 times normal), presence of auto-antibodies [(antinuclear antibodies (ANA)], smooth muscle antibody (SMA) and antibody to liver-kidney microsome type 1 (LKM1) in the absence of viral markers ie, hepatitis B (HBsAg) and C (AntiHCV) and excellent response to corticosteroid therapy.

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

Langerhans Cells Maintain Local Tissue Tolerance in a Model of Systemic Autoimmune Disease1

PubMed Central

King, Jennifer K.; Philips, Rachael L.; Eriksson, Anna U.; Kim, Peter J.; Halder, Ramesh C.; Lee, Delphine J.; Singh, Ram Raj

2015-01-01

Systemic autoimmune diseases such as lupus affect multiple organs, usually in a diverse fashion where only certain organs are affected in individual patients. It is unclear whether the ‘local’ immune cells play a role in regulating tissue specificity in relation to disease heterogeneity in systemic autoimmune diseases. Here, we used skin as a model to determine the role of tissue-resident dendritic cells in local and systemic involvement within a systemic lupus disease model. Skin-resident dendritic cells, namely Langerhans cells (LC), have been implicated in regulating tolerance or autoimmunity using elegant transgenic models, however, their role in local versus systemic immune regulation is unknown. We demonstrate that while lymphocytes from skin-draining lymph nodes of autoimmune-prone MRL/MpJ-Faslpr/lpr mice react spontaneously to a physiological skin self-Ag desmoglein-3, epicutaneous applications of desmoglein-3 induced tolerance that is dependent on LCs. Inducible ablation of LCs in adult, preclinical MRL/MpJ-Faslpr/lpr and MRL/MpJ-Fas+/+ mice resulted in increased autoantibodies against skin Ags and markedly accelerated lupus dermatitis with increased local macrophage infiltration, but had no effect on systemic autoantibodies such as anti-dsDNA Abs or disease in other organs such as kidneys, lung, and liver. Furthermore, skin-draining lymph nodes of LC-ablated MRL/MpJ-Faslpr/lpr mice had significantly fewer CD4+ T-cells producing anti-inflammatory cytokine IL-10 than LC-intact controls. These results indicate that a skin-resident dendritic cell population regulates local tolerance in systemic lupus and emphasize the importance of the local immune milieu in preventing tissue-specific autoimmunity yet have no effect on systemic autoimmunity. PMID:26071559

Association pernicious anemia and autoimmune polyendocrinopathy: a retrospective study

PubMed Central

Zulfiqar, AA; Andres, E

2017-01-01

Objective: To investigate the association between pernicious anemia and other autoimmune diseases. Methods: This retrospective and bicentric study was conducted at Reims and Strasbourg University Hospitals and involved 188 patients with pernicious anemia examined between 2000 and 2010 in order to search for other autoimmune diseases and to evaluate the role of pernicious anemia in autoimmune polyglandular syndrome. Results: A total of 74 patients with a combination of pernicious anemia and other autoimmune diseases were included in the study. Our study revealed the privileged association of pernicious anemia with autoimmune thyroiditis. The association of pernicious anemia and autoimmune thyroiditis are a part of the autoimmune polyglandular syndrome type 3b. Conclusion: We suggest undertaking a systematic clinical examination and laboratory investigations in search of autoimmune thyroiditis in patient(s) with the diagnosis of pernicious anemia. The association of pernicious anemia and autoimmune thyroiditis is frequent and a part of autoimmune polyglandular 3b. PMID:29362601

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

Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells.

PubMed

De Bellis, A; Sinisi, A A; Pane, E; Dello Iacovo, A; Bellastella, G; Di Scala, G; Falorni, A; Giavoli, C; Gasco, V; Giordano, R; Ambrosio, M R; Colao, A; Bizzarro, A; Bellastella, A

2012-10-01

Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism. Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism. We conducted a cross-sectional cohort study. Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects. AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA. AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells. The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

Genetic sharing and heritability of paediatric age of onset autoimmune diseases

PubMed Central

Li, Yun R.; Zhao, Sihai D.; Li, Jin; Bradfield, Jonathan P.; Mohebnasab, Maede; Steel, Laura; Kobie, Julie; Abrams, Debra J.; Mentch, Frank D.; Glessner, Joseph T.; Guo, Yiran; Wei, Zhi; Connolly, John J.; Cardinale, Christopher J.; Bakay, Marina; Li, Dong; Maggadottir, S. Melkorka; Thomas, Kelly A.; Qui, Haijun; Chiavacci, Rosetta M.; Kim, Cecilia E.; Wang, Fengxiang; Snyder, James; Flatø, Berit; Førre, Øystein; Denson, Lee A.; Thompson, Susan D.; Becker, Mara L.; Guthery, Stephen L.; Latiano, Anna; Perez, Elena; Resnick, Elena; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Silverberg, Mark S.; Lie, Benedicte A.; Punaro, Marilynn; Russell, Richard K.; Wilson, David C.; Dubinsky, Marla C.; Monos, Dimitri S.; Annese, Vito; Munro, Jane E.; Wise, Carol; Chapel, Helen; Cunningham-Rundles, Charlotte; Orange, Jordan S.; Behrens, Edward M.; Sullivan, Kathleen E.; Kugathasan, Subra; Griffiths, Anne M.; Satsangi, Jack; Grant, Struan F. A.; Sleiman, Patrick M. A.; Finkel, Terri H.; Polychronakos, Constantin; Baldassano, Robert N.; Luning Prak, Eline T.; Ellis, Justine A.; Li, Hongzhe; Keating, Brendan J.; Hakonarson, Hakon

2015-01-01

Autoimmune diseases (AIDs) are polygenic diseases affecting 7–10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP-h2). SNP-h2 estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP-h2 in T1D and JIA, but does not significantly contribute to the pairwise rG. Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations between autoimmune diseases previously reported in adult cohorts. PMID:26450413

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

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.

SIALIC ACIDS AND AUTOIMMUNE DISEASE

PubMed Central

Mahajan, Vinay S.; Pillai, Shiv

2016-01-01

summary 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

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

From microbiome to infectome in autoimmunity.

PubMed

Bogdanos, Dimitrios P; Sakkas, Lazaros I

2017-07-01

The current review discusses the pros and cons of the microbiome studies conducted in search of the association between microbiota and autoimmunity. We focus on the role of infectome and autoinfectome as a bridge to link the findings of microbiome studies with those emerging from investigations of the role of specific viruses and antiviral responses as triggers of autoimmunity (through various mechanisms such as molecular mimicry). The 'usual suspects', such as herpetoviruses and Escherichia coli, are thoroughly discussed in light of the data emerged by the microbiome studies, using as examples specific autoimmune rheumatic diseases and inflammatory bowel diseases. We conclude that the studies of the oral cavity, gastrointestinal, and urinary tract microbiome are informative but can only be useful if further explored from the infectome perspective. This means that the plethora of bacteria associated with autoimmune diseases from microbiome studies can be and must be tested experimentally. If certain bacteria are associated directly or indirectly with autoimmune diseases, specific immunological mechanisms must be identified.

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

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.

Persistent Changes in Circulating and Intestinal γδ T Cell Subsets, Invariant Natural Killer T Cells and Mucosal-Associated Invariant T Cells in Children and Adults with Coeliac Disease

PubMed Central

Dunne, Margaret R.; Elliott, Louise; Hussey, Seamus; Mahmud, Nasir; Kelly, Jacinta; Doherty, Derek G.; Feighery, Conleth F.

2013-01-01

Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56+ T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity. PMID:24124528

Persistent changes in circulating and intestinal γδ T cell subsets, invariant natural killer T cells and mucosal-associated invariant T cells in children and adults with coeliac disease.

PubMed

Dunne, Margaret R; Elliott, Louise; Hussey, Seamus; Mahmud, Nasir; Kelly, Jacinta; Doherty, Derek G; Feighery, Conleth F

2013-01-01

Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56(+) T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.

Bell's palsy and autoimmunity.

PubMed

Greco, A; Gallo, A; Fusconi, M; Marinelli, C; Macri, G F; de Vincentiis, M

2012-12-01

To review our current knowledge of the etiopathogenesis of Bell's palsy, including viral infection or autoimmunity, and to discuss disease pathogenesis with respect to pharmacotherapy. Relevant publications on the etiopathogenesis, clinical presentation, diagnosis and histopathology of Bell's palsy from 1975 to 2012 were analysed. Bell's palsy is an idiopathic peripheral nerve palsy involving the facial nerve. It accounts for 60 to 75% of all cases of unilateral facial paralysis. The annual incidence of Bell's palsy is 15 to 30 per 100,000 people. The peak incidence occurs between the second and fourth decades (15 to 45 years). The aetiology of Bell's palsy is unknown but viral infection or autoimmune disease has been postulated as possible pathomechanisms. Bell's palsy may be caused when latent herpes viruses (herpes simplex, herpes zoster) are reactivated from cranial nerve ganglia. A cell-mediated autoimmune mechanism against a myelin basic protein has been suggested for the pathogenesis of Bell's palsy. Bell's palsy may be an autoimmune demyelinating cranial neuritis, and in most cases, it is a mononeuritic variant of Guillain-Barré syndrome, a neurologic disorder with recognised cell-mediated immunity against peripheral nerve myelin antigens. In Bell's palsy and GBS, a viral infection or the reactivation of a latent virus may provoke an autoimmune reaction against peripheral nerve myelin components, leading to the demyelination of cranial nerves, especially the facial nerve. Given the safety profile of acyclovir, valacyclovir, and short-course oral corticosteroids, patients who present within three days of the onset of symptoms should be offered combination therapy. However it seems logical that in fact, steroids exert their beneficial effect via immunosuppressive action, as is the case in some other autoimmune disorders. It is to be hoped that (monoclonal) antibodies and/or T-cell immunotherapy might provide more specific treatment guidelines in the

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

Autoimmunity to protective molecules: is it the perpetuum mobile (vicious cycle) of autoimmune rheumatic diseases?

PubMed

Kravitz, Martine Szyper; Shoenfeld, Yehuda

2006-09-01

Apoptotic defects and impaired clearance of cellular debris are considered key events in the development of autoimmunity, as they can contribute to autoantigen overload and might be involved in the initiation of an autoimmune response. The C1q protein and mannose-binding lectin are activators of the complement system. The pentraxins are a group of highly conserved proteins including the short pentraxins, C-reactive protein and serum amyloid P, and the long pentraxin family member, pentraxin 3, all of which are involved in innate immunity and in acute-phase responses. In addition to their role in innate immunity and inflammation, each of these proteins participates in the removal of damaged and apoptotic cells. In this article, we discuss the clinical significance of different levels of these proteins, their role in the induction of or protection against autoimmunity, and the presence of specific autoantibodies against them in various autoimmune diseases.

[The autoimmune rheumatic disease and laryngeal pathology].

PubMed

Osipenko, E V; Kotel'nikova, N M

Vocal disorders make up one of the autoimmune pathological conditions characterized by multiple organ system dysfunction. Laryngeal pathology in this condition has an autoimmune nature; it is highly diverse and poorly explored. The objective of the present work based on the analysis of the relevant literature publications was to study clinical manifestations of the autoimmune rheumatic disease affecting the larynx. 'Bamboo nodes' on the vocal folds is a rare manifestation of laryngeal autoimmune diseases. We found out references to 49 cases of this condition in the available literature. All the patients were women presenting with autoimmune diseases. The present review highlights the problems pertaining to etiology of 'bamboo nodes' on the vocal folds and the method for the treatment of this condition.

Acrylamine-induced autoimmune phenomena.

PubMed

Rothschild, Bruce

2010-09-01

The objective of this study is to document a series of cases of occupationally derived autoimmune disease. Individuals with occupational exposure to acrylamides were evaluated clinically and biochemically/immunologically for evidence of autoimmune disease. Symptoms and signs and immuno-reactivity were monitored during exposure-free and re-exposure as part of the individuals' clinical evaluation. Six individuals with occupational acrylamide exposure had clinical and laboratory alterations characteristic of drug-induced autoimmune disease, specifically lupus, anti-phospholipid syndrome, Sjogren's syndrome, scleroderma, and polymyositis. The similarity of the full spectrum of disease in the reported patients to that found with procainamide strongly suggests the effects of occupational exposure. This uncontrolled study suggests the need for a full epidemiologic analysis of all individuals working with such occupational exposure, including full clinical and immunological examination.

Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rβ1 Deficiency.

PubMed

Arias, Andrés Augusto; Perez-Velez, Carlos M; Orrego, Julio César; Moncada-Velez, Marcela; Rojas, Jessica Lineth; Wilches, Alejandra; Restrepo, Andrea; Trujillo, Mónica; Garcés, Carlos; Arango-Ferreira, Catalina; González, Natalia; Oleaga-Quintas, Carmen; Fernández, Diana; Isaza-Correa, Johana Marcela; Gongóra, Diego Eduardo; Gonzalez-Loaiza, Daniel; Sierra, Juan Esteban; Casanova, Jean Laurent; Bustamante, Jacinta; Franco, José Luis

2017-10-01

Mendelian susceptibility to mycobacterial disease is a rare clinical condition characterized by a predisposition to infectious diseases caused by poorly virulent mycobacteria. Other infections such as salmonellosis and candidiasis are also reported. The purpose of this article is to describe a young boy affected with various infectious diseases caused by Mycobacterium tuberculosis complex, Salmonella sp, Klebsiella pneumonie, Citrobacter sp., and Candida sp, complicated with severe enteropathy and transient hypogammaglobulinemia. We reviewed medical records and performed flow cytometry staining for lymphocyte populations, lymphocyte proliferation in response to PHA, and intracellular IFN-γ production in T cell PHA blasts in the patient and a healthy control. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rβ1 deficiency. Functional analysis demonstrated the lack of intracellular production of IFN-γ in CD3+ T lymphocytes from the patient in response to rhIL-12p70. To our knowledge, this is the third patient with MSMD due to IL-12Rβ1 deficiency complicated with enteropathy and hypogammaglobulinemia and the first case of this disease to be described in Colombia.

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

Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthritis Following Lyme Disease.

PubMed

Arvikar, Sheila L; Crowley, Jameson T; Sulka, Katherine B; Steere, Allen C

2017-01-01

To describe systemic autoimmune joint diseases that develop following Lyme disease, and to compare their clinical features with those of Lyme arthritis (LA). We reviewed records of all adult patients referred to our LA clinic over a 13-year period, in whom we had diagnosed a systemic autoimmune joint disease following Lyme disease. For comparison, records of patients enrolled in our LA cohort over the most recent 2-year period were analyzed. Levels of IgG antibodies to Borrelia burgdorferi and to 3 Lyme disease-associated autoantigens were measured. We identified 30 patients who had developed a new-onset systemic autoimmune joint disorder a median of 4 months after Lyme disease (usually manifested by erythema migrans [EM]). Fifteen had rheumatoid arthritis (RA), 13 had psoriatic arthritis (PsA), and 2 had peripheral spondyloarthritis (SpA). The 30 patients typically had polyarthritis, and those with PsA or SpA often had previous psoriasis, axial involvement, or enthesitis. In the comparison group of 43 patients with LA, the usual clinical picture was monoarticular knee arthritis, without prior EM. Most of the patients with systemic autoimmune joint disorders were positive for B burgdorferi IgG antibodies, as detected by enzyme-linked immunosorbent assay, but had significantly lower titers and lower frequencies of Lyme disease-associated autoantibodies than patients with LA. Prior to our evaluation, these patients had often received additional antibiotics for presumed LA, without benefit. We prescribed antiinflammatory agents, most commonly disease-modifying antirheumatic drugs, resulting in improvement. Systemic autoimmune joint diseases (i.e., RA, PsA, SpA) may follow Lyme disease. Development of polyarthritis after antibiotic-treated EM, previous psoriasis, or low-titer B burgdorferi antibodies may provide insight into the correct diagnosis. © 2016, American College of Rheumatology.

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

Human neutrophils in auto-immunity.

PubMed

Thieblemont, Nathalie; Wright, Helen L; Edwards, Steven W; Witko-Sarsat, Véronique

2016-04-01

Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS), proteases and other tissue-damaging molecules. Furthermore, activated neutrophils can release a wide variety of cytokines and chemokines that can regulate almost every element of the immune system. In addition to these important immuno-regulatory processes, activated neutrophils can also release, expose or generate neoepitopes that have the potential to break immune tolerance and result in the generation of autoantibodies, that characterise a number of human auto-immune diseases. For example, in vasculitis, anti-neutrophil cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are the main effector cells of vascular damage. In other auto-immune diseases, these neutrophil-derived neoepitopes may arise from a number of processes that include release of granule enzymes and ROS, changes in the properties of components of their plasma membrane as a result of activation or apoptosis, and via the release of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that contain chromatin that is decorated with granule enzymes (including citrullinated proteins) that can act as neo-epitopes to generate auto-immunity. This review therefore describes the processes that can result in neutrophil-mediated auto-immunity, and the role of neutrophils in the molecular pathologies of auto-immune diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We discuss the potential role of NETs in these processes and some of the debate in the literature regarding the role of this phenomenon in microbial killing, cell death and auto-immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bacterial β-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: mode of action and pharmacokinetics

PubMed Central

Saitta, Kyle S.; Zhang, Carmen; Lee, Kang Kwang; Fujimoto, Kazunori; Redinbo, Matthew R.; Boelsterli, Urs A.

2014-01-01

We have previously demonstrated that a small molecule inhibitor of bacterial β-glucuronidase (Inh-1; [1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea]) protected mice against diclofenac (DCF)-induced enteropathy. Here we report that Inh-1 was equally protective against small intestinal injury induced by other carboxylic acid-containing non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin (10 mg/kg, ip) and ketoprofen (100 mg/kg, ip).Inh-1 provided complete protection if given prior to DCF (60 mg/kg, ip), and partial protection if administered 3-h post-DCF, suggesting that the temporal window of mucosal protection can be extended for drugs undergoing extensive enterohepatic circulation.Pharmacokinetic analysis of Inh-1 revealed an absolute bioavailability (F) of 21% and a short t1/2 of <1 h. This low F was shown to be due to hepatic first-pass metabolism, as confirmed with the pan-CYP inhibitor, 1-aminobenzotriazole.Using the fluorescent probe 5 (and 6)-carboxy-2′,7′-dichlorofluorescein, we demonstrated that Inh-1 did not interfere with hepatobiliary export of glucuronides in gall bladder-cannulated mice.These data are compatible with the hypothesis that pharmacological inhibition of bacterial β-glucuronidase-mediated cleavage of NSAID glucuronides in the small intestinal lumen can protect against NSAID-induced enteropathy caused by locally high concentrations of NSAID aglycones. PMID:23829165

Autoimmunity in 2016.

PubMed

Selmi, Carlo

2017-08-01

The number of peer-reviewed articles published during the 2016 solar year and retrieved using the "autoimmunity" key word remained stable while gaining a minimal edge among the immunology articles. Nonetheless, the quality of the publications has been rising significantly and, importantly, acquisitions have become available through scientific journals dedicated to immunology or autoimmunity. Major discoveries have been made in the fields of systemic lupus erythematosus, rheumatoid arthritis, autoimmunity of the central nervous system, vasculitis, and seronegative spondyloarthrithritides. Selected examples include the role of IL17-related genes and long noncoding RNAs in systemic lupus erythematosus or the effects of anti-pentraxin 3 (PTX3) in the treatment of this paradigmatic autoimmune condition. In the case of rheumatoid arthritis, there have been reports of the role of induced regulatory T cells (iTregs) or fibrocytes and T cell interactions with exciting implications. The large number of studies dealing with neuroimmunology pointed to Th17 cells, CD56(bright) NK cells, and low-level TLR2 ligands as involved in multiple sclerosis, along with a high salt intake or the micriobiome-derived Lipid 654. Lastly, we focused on the rare vasculitides to which numerous studies were devoted and suggested that unsuspected cell populations, including monocytes, mucosal-associated invariant T cells, and innate lymphoid cells, may be crucial to ANCA-associated manifestations. This brief and arbitrary discussion of the findings published in 2016 is representative of a promising background for developments that will enormously impact the work of laboratory scientists and physicians at an exponential rate.

Autoimmune hepatitis.

PubMed

Vergani, D; Mieli-Vergani, G

2004-06-01

Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.

The Diagnostic Challenges of Autoimmune Pancreatitis

PubMed Central

Papp, Kata; Angst, Eliane; Seidel, Stefan; Flury-Frei, Renata; Hetzer, Franc Heinrich

2015-01-01

Autoimmune pancreatitis is a rare but important differential diagnosis from pancreatic cancer. This autoimmune disease can mimic pancreatic cancer by its clinical symptoms, including weight loss and jaundice. Furthermore imaging findings may include a mass of the pancreas. Here we present the case of a 67-year-old male patient diagnosed with autoimmune pancreatitis but showing the well-known symptoms of pancreatic cancer. This emphasizes the difficulties of histological findings and the importance of the correct diagnostic process. PMID:25802499

Genetic variation associated with cardiovascular risk in autoimmune diseases

PubMed Central

Perrotti, Pedro P.; Aterido, Adrià; Fernández-Nebro, Antonio; Cañete, Juan D.; Ferrándiz, Carlos; Tornero, Jesús; Gisbert, Javier P.; Domènech, Eugeni; Fernández-Gutiérrez, Benjamín; Gomollón, Fernando; García-Planella, Esther; Fernández, Emilia; Sanmartí, Raimon; Gratacós, Jordi; Martínez-Taboada, Víctor Manuel; Rodríguez-Rodríguez, Luís; Palau, Núria; Tortosa, Raül; Corbeto, Mireia L.; Lasanta, María L.; Marsal, Sara; Julià, Antonio

2017-01-01

Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity. PMID:28982122

Autoimmune disorders

MedlinePlus

... exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or ... the thyroid or pancreas Joints Muscles Red blood cells Skin A person may have more than one ...

Autoimmunity in focus: from mechanisms to treatment.

PubMed

Kon, Yujiro

2012-05-01

The 5th Asian Congress on Autoimmunity took place in Suntec City, Singapore, on the 17-19 November 2011 under the presidency of Yehuda Shoenfeld (Chaim Sheba Medical Center, Ramat Gan, Israel). Senior investigators from a range of fields--including immunology, autoimmunity, rheumatology, neurology and hepatology--attended the conference. The scientific program placed an emphasis on the pathogenesis, genetic basis and mechanistic aspects of autoimmune diseases, as well as their clinical outcomes and treatment options. Particular focus was placed on systemic lupus erythematosus, rheumatoid arthritis, Type I diabetes, antiphospholipid syndrome and autoimmune hepatitis. Participants from over 50 countries attended the conference.

Monogenic autoimmune diseases of the endocrine system.

PubMed

Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E

2016-10-01

The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical Recommendations for the Use of Islet Cell Autoantibodies to Distinguish Autoimmune and Non-Autoimmune Gestational Diabetes.

PubMed

Haller-Kikkatalo, Kadri; Uibo, Raivo

2016-02-01

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that begins or is first recognized during pregnancy. The prevalence of GDM is highly variable, depending on the population studied, and reflects the underlying pattern of diabetes in the population. GDM manifests by the second half of pregnancy and disappears following delivery in most cases, but is associated with the risk of subsequent diabetes development. Normal pregnancy induces carbohydrate intolerance to favor the availability of nutrients for the fetus, which is compensated by increased insulin secretion from the maternal pancreas. Pregnancy shares similarities with adiposity in metabolism to save energy, and both conditions favor the development of insulin resistance (IR) and low-grade inflammation. A highly complicated network of modified regulatory mechanisms may primarily affect carbohydrate metabolism by promoting autoimmune reactions to pancreatic β cells and affecting insulin function. As a result, diabetes development during pregnancy is facilitated. Depending on a pregnant woman's genetic susceptibility to diabetes, autoimmune mechanisms or IR are fundamental to the development autoimmune or non-autoimmune GDM, respectively. Pregnancy may facilitate the identification of women at risk of developing diabetes later in life; autoimmune and non-autoimmune GDM may be early markers of the risk of future type 1 and type 2 diabetes, respectively. The most convenient and efficient way to discriminate GDM types is to assess pancreatic β-cell autoantibodies along with diagnosing diabetes in pregnancy.

Insulinotropic and Anti-Inflammatory Effects of Rosiglitazone in Experimental Autoimmune Diabetes

PubMed Central

Awara, Wageh M.; El-Sisi, Alaa E.; El-Refaei, Mohamed; El-Naa, Mona M.; El-Desoky, Karima

2005-01-01

Cytokines and nitric oxide (NO) are involved in the pathogenesis of autoimmune diabetes mellitus (DM). Rosiglitazone is an insulin-sensitizing drug that is a ligand for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ). The anti-inflammatory and immunomodulating properties of PPAR-γ have been documented. The aim of this study is to investigate the effectiveness of rosiglitazone in autoimmune DM and to clarify the possible mechanism(s) involved. Autoimmune DM was induced in adult male Balb/c mice by co-administration of cyclosporin A and multiple low doses of streptozotocin. Diabetic mice were treated daily with rosiglitazone (7 mg/kg, p.o.) for 21 days. Blood glucose level (BGL), serum insulin level and pancreatic levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and NO were measured. Histopathological examination and immunohistochemical determination of CD4 and CD8 T lymphocytes in the pancreatic islets were performed. In addition, analysis of pancreatic protein expression was carried out. The results showed that rosiglitazone treatment resulted in a significant decrease in the BGL and the pancreatic levels of TNF-α, IFN-γ and NO compared to diabetic mice. The serum insulin level was significantly increased after rosiglitazone treatment compared to diabetic mice. The destroyed pancreatic islets were regenerated and became free from both CD4 and CD8 T cells after treatment. Furthermore, many changes in pancreatic protein expression were observed. These results suggest that rosiglitazone has a beneficial effect in the treatment of autoimmune diabetes, an effect that seemed to be a secondary consequence of its anti-inflammatory and immunomodulating properties and might be reflected at the level of protein expression. PMID:17491689

The value of Autoimmune Syndrome Induced by Adjuvant (ASIA) - Shedding light on orphan diseases in autoimmunity.

PubMed

Segal, Yahel; Dahan, Shani; Sharif, Kassem; Bragazzi, Nicola Luigi; Watad, Abdulla; Amital, Howard

2018-05-01

Autoimmune Syndrome Induced by Adjuvant (ASIA) is a definition aimed to describe the common etiological process at the root of five clinical entities sharing similar symptomatology: macrophagic myofasciitis syndrome (MMF), Gulf War Syndrome (GWS), sick building syndrome (SBS), siliconosis, and post vaccination autoimmune phenomena. ASIA illustrates the role of environmental immune stimulating agents, or adjuvants, in the instigation of complex autoimmune reactions among individuals bearing a genetic preponderance for autoimmunity. The value of ASIA lies first in the acknowledgment it provides for patients suffering from these as yet ill-defined medical conditions. Equally important is the spotlight it sheds for further research of these poorly understood conditions sharing a common pathogenesis. In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity. Copyright © 2018 Elsevier B.V. All rights reserved.

Diagnosing autoimmune pancreatitis with the Unifying-Autoimmune-Pancreatitis-Criteria.

PubMed

Schneider, Alexander; Michaely, Henrik; Rückert, Felix; Weiss, Christel; Ströbel, Philipp; Belle, Sebastian; Hirth, Michael; Wilhelm, Torsten J; Haas, Stephan L; Jesenofsky, Ralf; Schönberg, Stefan; Marx, Alexander; Singer, Manfred V; Ebert, Matthias P; Pfützer, Roland H; Löhr, J Matthias

We had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pancreatitis (AiP) within the M-ANNHEIM classification of chronic pancreatitis. In 2011, International-Consensus-Diagnostic-Criteria (ICDC) to diagnose AiP have been published. We had applied the U-AIP long before the ICDC were available. The aims of the study were, first, to describe patients with AiP diagnosed by the U-AIP; second, to compare diagnostic accuracies of the U-AIP and other diagnostic systems; third, to evaluate the clinical applicability of the U-AIP. From 1998 until 2008, we identified patients with AiP using U-AIP, Japanese-, Korean-, Asian-, Mayo-HISORt-, Revised-Mayo-HISORt- and Italian-criteria. We retrospectively verified the diagnosis by ICDC and Revised-Japanese-2011-criteria, compared diagnostic accuracies of all systems and evaluated all criteria in consecutive patients with pancreatitis (2009 until 2010, Pancreas-Outpatient-Clinic-Cohort, n = 84). We retrospectively validated our diagnostic approach in consecutive patients with a pancreatic lesion requiring surgery (Surgical-Cohort, n = 98). Overall, we identified 21 patients with AiP. Unifying-Autoimmune-Pancreatitis-Criteria and ICDC presented the highest diagnostic accuracies (each 98.8%), highest Youden indices (each 0.95238), and highest proportions of diagnosed patients (each n = 20/21, U-AIP/ICDC vs. other diagnostic systems, p < 0.05, McNemar test). In the Pancreas-Outpatient-Clinic-Cohort, seven patients were diagnosed with AiP (n = 6 by U-AIP, n = 1 by Asian-criteria). International-Consensus-Diagnostic-Criteria confirmed the diagnosis in these individuals. Based on partial fulfillment of U-AIP, AiP was initially suspected in 13% (n = 10/77) of remaining patients from the Pancreas-Outpatient-Clinic-Cohort. In the Surgical-cohort, we identified one patient with AiP by U-AIP and ICDC. Unifying-Autoimmune-Pancreatitis-Criteria revealed a satisfactory clinical applicability

[Autoantibodies, tolerance and autoimmunity].

PubMed

Oppezzo, Pablo; Dighiero, Guillaume

2003-07-01

In 1900, the group from Metchnikoff suggested the concept of autoimmunization by demonstrating the presence of autoantibodies in normal conditions; which was opposed to the concept of horror autotoxicus raised by Ehrlich. Landsteiner's description of the transfusion compatibility rules and 50 year-later work from Burnett's and Medawar's groups lead to the clonal deletion theory as a general explanation of tolerance and autoimmunity. However, more recent work succeeded demonstrating that autoreactive B cells constitute a substantial part of the B-cell repertoire and that this autoreactive repertoire secretes the so-called natural autoantibodies (NAA) characterized by their broad reactivity mainly directed against very well conserved public epitopes. They fulfill the definition of an autoantibody since they are self-reactive, but they are not self-specific. As yet, NAA directed against determinants of polymorphism have not been reported. The presence of this repertoire in normal conditions challenges the clonal deletion theory as a unique explanation for self-tolerance. However, if we take into account that this autoreactive B-cell repertoire is not self-specific, this contradiction may not be a real one opposition. Indeed, the Lansteiner's rule that a subject belonging to group A will never produce anti-A antibodies and will always produce natural antibodies against the B-cell group, could never be challenged. Clonal deletion is probably accounting for this phenomenum. However, the serum of healthy adult individuals frequently exhibits low titers of anti-I antibodies, which is a precursor molecule of AB0 antigen system. The mechanism accounting for deletion of B cells directed against critical determinants like antigens A and B in the red blood cell system and allowing the production of autoantibodies against I remain elusive.

[MAIT cells in autoimmunity].

PubMed

Miyake, Sachiko

2014-01-01

Mucosal associated invariant T (MAIT) cells express a semi-invariant TCRα chain: Vα7.2-Jα33 in humans and Vα19-Jα33 in mice. They are restricted by a nonpolymorphic MHC-related molecule-1 (MR1), and cells are selected in the thymus. Interestingly, MAIT cells require B cells as well as commensal flora for their peripheral expansion. MAIT cells display antimicrobial capacity. Recently, vitamin metabolites were demonstrated as antigens created by intestinal flora for MAIT cells. MAIT cells play a protective role against autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), wheras they play a pathogenic role in murine models of arthritis. In patients with autoimmune diseases, the frequency of MAIT cells in peripheral blood was significantly reduced. The frequency of MAIT cells reflected the disease activity in MS patients, suggesting the involvement of MAIT cells in the regulation of autoimmune diseases.

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis.

PubMed

Martin, Roland; Sospedra, Mireia; Rosito, Maria; Engelhardt, Britta

2016-09-01

Multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system (CNS) in young adults. When MS is not treated, it leads to irreversible and severe disability. The etiology of MS and its pathogenesis are not fully understood. The recent discovery that MS-associated genetic variants code for molecules related to the function of specific immune cell subsets is consistent with the concept of MS as a prototypic, T-cell-mediated autoimmune disease targeting the CNS. While the therapeutic efficacy of the currently available immunomodulatory therapies further strengthen this concept, differences observed in responses to MS treatment as well as additional clinical and imaging observations have also shown that the autoimmune pathogenesis underlying MS is much more complex than previously thought. There is therefore an unmet need for continued detailed phenotypic and functional analysis of disease-relevant adaptive immune cells and tissues directly derived from MS patients to unravel the immune etiology of MS in its entire complexity. In this review, we will discuss the currently available MS treatment options and approved drugs, including how they have contributed to the understanding of the immune pathology of this autoimmune disease. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Clinical characterization of autoimmune encephalitis and psychosis.

PubMed

Hao, Qinjian; Wang, Dahai; Guo, Lanting; Zhang, Bo

2017-04-01

Autoimmune disorders are growing alarmingly high in prevalence across the globe. Autoimmune encephalitis has had a dramatic impact on the medical field, effectually altering diagnostic and treatment paradigms in regard to neuropsychiatric disorders. Our primary goal in conducting this study was to analyze the clinical characteristics of autoimmune encephalitis patients, with special focus on psychiatric presentations, in the West China Hospital and report patient prognoses after immunotherapy. Data for patients admitted to the West China Hospital with autoimmune encephalitis diagnoses from 2015 to 2016 were collected and the corresponding clinical features were analyzed. We ultimately included 70 patients with autoimmune encephalitis: 56 (80%) anti-NMDAR encephalitis patients, 8 (11%) LGI1 antibody encephalitis patients, and 6 (9%) GABAbR antibody encephalitis patients. The median age of the 70 patients was 33years, 40% were female, and the initial symptoms in 31 patients (44%) were psychiatric in nature. Psychiatric disturbance appeared in 58 patients (83%) during inpatient treatment, after which 57 patients (81%) recovered. Many patients with autoimmune encephalitis present psychotic symptoms; psychiatric symptoms typically appear before neurological features emerge. Timely diagnosis and treatment may yield favorable prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Thyroid Autoimmunity in Girls with Turner Syndrome.

PubMed

Witkowska-Sędek, Ewelina; Borowiec, Ada; Kucharska, Anna; Chacewicz, Karolina; Rumińska, Małgorzata; Demkow, Urszula; Pyrżak, Beata

2017-01-01

Turner syndrome is associated with increased incidence of autoimmune diseases, especially those of the thyroid gland. The aim of this study was to assess the prevalence of thyroid autoimmunity among pediatric patients with Turner syndrome. The study was retrospective and included 41 girls with Turner syndrome aged 6-18 years. Free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (TPO-Ab) antibodies, anti-thyroglobulin (TG-Ab) antibodies, and karyotype were investigated. The correlation between karyotype and incidence of thyroid autoimmunity was also examined. Eleven patients (26.8%) were positive for TPO-Ab and/or TG-Ab. Three girls from that subgroup were euthyroid, 5 had subclinical hypothyroidism, and 3 were diagnosed with overt hypothyroidism. Out of these 11 patients affected by thyroid autoimmunity, 6 girls had mosaic karyotype with X-isochromosome (n = 4) or with deletions (n = 2), and 5 had the 45,X karyotype. The study findings confirmed a high incidence of thyroid autoimmunity in girls with Turner syndrome, but we failed to observe an association between the incidence of thyroid autoimmunity and karyotype. We conclude that it is important to monitor thyroid function in patients with Turner syndrome because they are prone to develop hypothyroidism.

Anti-Saccharomyces cerevisiae autoantibodies in autoimmune diseases: from bread baking to autoimmunity.

PubMed

Rinaldi, Maurizio; Perricone, Roberto; Blank, Miri; Perricone, Carlo; Shoenfeld, Yehuda

2013-10-01

Saccharomyces cerevisiae is best known as the baker's and brewer's yeast, but its residual traces are also frequent excipients in some vaccines. Although anti-S. cerevisiae autoantibodies (ASCAs) are considered specific for Crohn's disease, a growing number of studies have detected high levels of ASCAs in patients affected with autoimmune diseases as compared with healthy controls, including antiphospholipid syndrome, systemic lupus erythematosus, type 1 diabetes mellitus, and rheumatoid arthritis. Commensal microorganisms such as Saccharomyces are required for nutrition, proper development of Peyer's aggregated lymphoid tissue, and tissue healing. However, even the commensal nonclassically pathogenic microbiota can trigger autoimmunity when fine regulation of immune tolerance does not work properly. For our purposes, the protein database of the National Center for Biotechnology Information (NCBI) was consulted, comparing Saccharomyces mannan to several molecules with a pathogenetic role in autoimmune diseases. Thanks to the NCBI bioinformation technology tool, several overlaps in molecular structures (50-100 %) were identified when yeast mannan, and the most common autoantigens were compared. The autoantigen U2 snRNP B″ was found to conserve a superfamily protein domain that shares 83 % of the S. cerevisiae mannan sequence. Furthermore, ASCAs may be present years before the diagnosis of some associated autoimmune diseases as they were retrospectively found in the preserved blood samples of soldiers who became affected by Crohn's disease years later. Our results strongly suggest that ASCAs' role in clinical practice should be better addressed in order to evaluate their predictive or prognostic relevance.

Autoimmune Addison's disease.

PubMed

Napier, Catherine; Pearce, Simon H S

2012-12-01

Addison's disease is a rare autoimmune disorder. In the developed world, autoimmune adrenalitis is the commonest cause of primary adrenal insufficiency, where the majority of patients have circulating antibodies against the key steroidogenic enzyme 21-hydroxylase. A complex interplay of genetic, immunological and environmental factors culminates in symptomatic adrenocortical insufficiency, with symptoms typically developing over months to years. Biochemical evaluation and further targeted investigations must confirm primary adrenal failure and establish the underlying aetiology. The diagnosis of adrenocortical insufficiency will necessitate lifelong glucocorticoid and mineralocorticoid replacement therapy, aiming to emulate physiological patterns of hormone secretion to achieve well-being and good quality of life. Education of patients and healthcare professionals is essential to minimise the risk of a life-threatening adrenal crisis, which must be promptly recognised and aggressively managed when it does occur. This article provides an overview of our current understanding of the natural history and underlying genetic and immunological basis of this condition. Future research may reveal novel therapeutic strategies for patient management. Until then, optimisation of pharmacological intervention and continued emphasis on education and empowerment of patients should underpin the management of individuals with autoimmune Addison's disease. Copyright © 2012. Published by Elsevier Masson SAS.

An Autoimmune Myositis-Overlap Syndrome Associated With Autoantibodies to Nuclear Pore Complexes

PubMed Central

Senécal, Jean-Luc; Isabelle, Catherine; Fritzler, Marvin J.; Targoff, Ira N.; Goldstein, Rose; Gagné, Michel; Raynauld, Jean-Pierre; Joyal, France; Troyanov, Yves; Dabauvalle, Marie-Christine

2014-01-01

Abstract Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr). By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults. Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic

[Autoimmune hepatitis: Immunological diagnosis].

PubMed

Brahim, Imane; Brahim, Ikram; Hazime, Raja; Admou, Brahim

2017-11-01

Autoimmune hepatopathies (AIHT) including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune cholangitis (AIC), represent an impressive entities in clinical practice. Their pathogenesis is not perfectly elucidated. Several factors are involved in the initiation of hepatic autoimmune and inflammatory phenomena such as genetic predisposition, molecular mimicry and/or abnormalities of T-regulatory lymphocytes. AIHT have a wide spectrum of presentation, ranging from asymptomatic forms to severe acute liver failure. The diagnosis of AIHT is based on the presence of hyperglobulinemia, cytolysis, cholestasis, typical even specific circulating auto-antibodies, distinctive of AIH or PBC, and histological abnormalities as well as necrosis and inflammation. Anti-F actin, anti-LKM1, anti-LC1 antibodies permit to distinguish between AIH type 1 and AIH type 2. Anti-SLA/LP antibodies are rather associated to more severe hepatitis, and particularly useful for the diagnosis of seronegative AIH for other the antibodies. Due to the relevant diagnostic value of anti-M2, anti-Sp100, and anti-gp210 antibodies, the diagnosis of PBC is more affordable than that of PSC and AIC. Based on clinical data, the immunological diagnosis of AIHT takes advantage of the various specialized laboratory techniques including immunofluorescence, immunodot or blot, and the Elisa systems, provided of a closer collaboration between the biologist and the physician. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Vaccination and autoimmunity-'vaccinosis': a dangerous liaison?

PubMed

Shoenfeld, Y; Aron-Maor, A

2000-02-01

The question of a connection between vaccination and autoimmune illness (or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatitis B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have been found in patients vaccinated against those diseases. Other autoimmune illnesses have been associated with vaccinations. Tetanus toxoid, influenza vaccines, polio vaccine, and others, have been related to phenomena ranging from autoantibodies production to full-blown illness (such as rheumatoid arthritis (RA)). Conflicting data exists regarding also the connection between autism and vaccination with measles vaccine. So far only one controlled study of an experimental animal model has been published, in which the possible causal relation between vaccines and autoimmune findings has been examined: in healthy puppies immunized with a variety of commonly given vaccines, a variety of autoantibodies have been documented but no frank autoimmune illness was recorded. The findings could also represent a polyclonal activation (adjuvant reaction). The mechanism (or mechanisms) of autoimmune reactions following immunization has not yet been elucidated. One of the possibilities is molecular mimicry; when a structural similarity exists between some viral antigen (or other component of the vaccine) and a self-antigen. This similarity may be the trigger to the autoimmune reaction. Other possible mechanisms are discussed. Even though the data regarding the relation between vaccination and autoimmune disease is conflicting, it seems that some autoimmune phenomena are clearly related to immunization (e.g. Guillain-Barre syndrome). The issue of the risk of vaccination remains a philosophical one, since to date the advantages of this policy have not been refuted, while the risk for autoimmune disease has not been irrevocably proved. We discuss the pros and cons of this

Epizootic rabbit enteropathy inoculum (TEC4): antibiograms and antibiotic fractionation.

PubMed

Huybens, Nathalie; Houeix, Julien; Licois, Dominique; Mainil, Jacques; Marlier, Didier

2011-01-01

Epizootic rabbit enteropathy (ERE) emerged and spread in Europe within the last 13 years causing major economical loss. The aims of the study was to evaluate antibiograms of TEC4, an inoculum composed of an extract of intestinal content of affected rabbits, and to test the potential of different antibiotic-based TEC4 fractions to reproduce the disease. Twenty nine different antibiotic discs were incubated for determining bacteria resistance. In a complementary study, nine tubes of liquid medium were inoculated with TEC4, incubated and added individually with amoxicillin/clavulanic acid, bacitracin, ceftiofur, doxycycline, novobiocin, streptomycyin, tylosin, vancomycin and 0.9% saline solution as control. The content of each tube was washed by centrifugation and suspended in saline. The three most effective antibiotics are florfenicol, amoxycillin/clavulanic acid and tylosin. A high concentration of Clostridium sordelli and Bacillus firmus were isolated in all fractions. Species never cultured from TEC4 were identified as Fusobacterium necrogenes (in vancomycin fraction), Cellulomonas sp (in novobiocin fraction) and Bacteroides distasonis (in doxycycline fraction). The ERE was reproduced when bacitracin, doxycycline and 0.9% fractions were inoculated. Rabbits showed ERE clinical signs with the specific drop in daily weight gain.

Use of tylvalosin-medicated feed to control porcine proliferative enteropathy.

PubMed

Guedes, R M C; França, S A; Machado, G S; Blumer, M A; da Costa Cruz, E C

2009-09-19

The effect of an oral treatment with the tartrate salt of tylvalosin on the development of proliferative enteropathy in 60 experimentally challenged pigs was studied. Thirty of the pigs were fed a diet medicated with 50 ppm tylvalosin and 30 were fed the unmedicated diet. The treated animals started to receive the medicated feed the day before they were inoculated, and continued to receive it for 14 days. The pigs' bodyweight, feed consumption and clinical signs were evaluated, and they were examined postmortem 20 days after inoculation, and samples of ileum were collected for immunohistochemistry (IHC) for Lawsonia intracellularis. Clinical signs of the disease were more evident in the untreated group than in the treated group. The average daily weight gain, average daily feed consumption and feed conversion efficiency were better in the treated group. The combined length of intestine with lesions was 2847 cm in the untreated group and 183 cm in the treated group. The tylvalosin treatment significantly reduced the level of L intracellularis infection; almost half of the treated pigs were IHC-negative compared with 3.3 per cent of the untreated pigs.

Recommendations to report and interpret HLA genetic findings in coeliac disease.

PubMed

Núñez, Concepción; Garrote, José Antonio; Arranz, Eduardo; Bilbao, José Ramón; Fernández Bañares, Fernando; Jiménez, Juana; Perucho, Teresa; Ruiz Casares, Eva; Sánchez-Valverde, Félix; Serrano, Nacho

2018-05-03

Coeliac disease (CD) is a chronic autoimmune enteropathy triggered by gluten and related prolamines in genetically predisposed individuals. Although CD is a polygenic disease, there is a strong association with genes of the human leukocyte antigen (HLA) region. Most patients present the HLA-DQ2 heterodimer, specifically the DQ2.5 isoform, which is present in around 90-96% of patients of European ancestry.

Autoimmunity-Basics and link with periodontal disease.

PubMed

Kaur, Gagandeep; Mohindra, Kanika; Singla, Shifali

2017-01-01

Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self-reactive lymphocytes. Periodontal diseases are characterized by inflammatory conditions that directly affect teeth-supporting structures, which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidence of involvement of immunopathology has been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T-cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Autoimmune mechanisms in pernicious anaemia & thyroid disease.

PubMed

Osborne, David; Sobczyńska-Malefora, Agata

2015-09-01

Pernicious anaemia (PA) and some types of thyroid disease result from autoimmune processes. The autoimmune mechanisms in these conditions have not been fully elucidated. This review discusses the autoimmune mechanisms involved in PA and how these affect diagnosis and disease progression. In addition to gastric antibodies, antibodies to the vitamin B12 binding protein transcobalamin which can result in high serum B12 levels are also addressed with regard to how they affect clinical practice. The role of autoimmune susceptibility is investigated by comparing PA to one of its most common comorbidities, autoimmune thyroid disease (AITD). Thyroid disease (although not exclusively AITD) and B12 deficiency are both also implicated in the pathology of hyperhomocysteinemia, an elevated homocysteine in plasma. Since hyperhomocysteinemia is a risk factor for cardiovascular occlusive disease, this review also addresses how thyroid disease in particular leads to changes in homocysteine levels. Copyright © 2015 Elsevier B.V. All rights reserved.

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Frequency of autoimmune diseases in myasthenia gravis: a systematic review.

PubMed

Mao, Zhi-Feng; Yang, Long-Xiu; Mo, Xue-An; Qin, Chao; Lai, Yong-Rong; He, Ning-Yu; Li, Tong; Hackett, Maree L

2011-03-01

The course of myasthenia gravis (MG) may get complicated by the development of other autoimmune diseases. Estimates of the frequency of autoimmune diseases will help inform patients and physicians, direct health policy discussion, provide etiologic clues, and optimize the management of MG. However, the frequency of autoimmune diseases in people with MG is still uncertain. A systematic search for English language studies was conducted by MEDLINE and EMBASE from 1960 through 2010. Incidence studies and case series of all MG subtypes with information about autoimmune diseases were included; 25 studies met the inclusion criteria. Although there was considerable heterogeneity, the pooled estimate of the coexisting autoimmune diseases in MG was 13% (95% confidence interval, 12%-14%). Autoimmune thyroid disease seems to occur more frequently than other autoimmune conditions in MG patients. Heterogeneity in study estimates could be explained by ascertainment bias and case mix. Furthermore, autoimmune diseases occurred significantly more often in females and anti-acetylcholine receptor seropositive MG patients. Patients with MG have an increased frequency of coexisting autoimmune diseases. Autoimmune diseases seem to occur more often in female and seropositive MG patients. Further research is needed to expand our understanding of these associations.

Upper gastrointestinal symptoms in autoimmune gastritis

PubMed Central

Carabotti, Marilia; Lahner, Edith; Esposito, Gianluca; Sacchi, Maria Carlotta; Severi, Carola; Annibale, Bruno

2017-01-01

Abstract Autoimmune gastritis is often suspected for its hematologic findings, and rarely the diagnosis is made for the presence of gastrointestinal symptoms. Aims of this cross-sectional study were to assess in a large cohort of patients affected by autoimmune gastritis the occurrence and the pattern of gastrointestinal symptoms and to evaluate whether symptomatic patients are characterized by specific clinical features. Gastrointestinal symptoms of 379 consecutive autoimmune gastritis patients were systematically assessed and classified following Rome III Criteria. Association between symptoms and anemia pattern, positivity to gastric autoantibodies, Helicobacter pylori infection, and concomitant autoimmune disease were evaluated. In total, 70.2% of patients were female, median age 55 years (range 17–83). Pernicious anemia (53.6%), iron deficiency anemia (34.8%), gastric autoantibodies (68.8%), and autoimmune disorders (41.7%) were present. However, 56.7% of patients complained of gastrointestinal symptoms, 69.8% of them had exclusively upper symptoms, 15.8% only lower and 14.4% concomitant upper and lower symptoms. Dyspepsia, subtype postprandial distress syndrome was the most represented, being present in 60.2% of symptomatic patients. Univariate and multivariate analyses showed that age <55 years (OR 1.6 [CI:1–2.5]), absence of smoking habit (OR 2.2 [CI:1.2–4]), and absence of anemia (OR 3.1 [CI:1.5–6.4]) were independent factors associated to dyspepsia. Autoimmune gastritis is associated in almost 60% of cases with gastrointestinal symptoms, in particular dyspepsia. Dyspepsia is strictly related to younger age, no smoking, and absence of anemia. PMID:28072728

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. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

[Clinical Phenomenology of Autoimmune Encephalitis].

PubMed

Holle, J F; Jessen, F; Kuhn, J

2016-05-01

Antibody-associated disorders of the central nervous system constitute a heterogeneous group of disorders that can be roughly divided into two categories: Classic paraneoplastic syndromes associated with so-called well-characterized antibodies (paraneoplastic neurological disorders, PND) and autoimmune disorders with antibodies to membrane-bound or synaptic antigens (autoimmune encephalitis, AE). The discovery of autoimmune encephalitis has led to a paradigm shift in diagnosis and therapy as well as a reclassification of some neuropsychiatric syndromes that were previously classified as idiopathic or simply covered with descriptive terms.In this review article, especially clinical aspects of autoimmune encephalitis will be discussed, as there has been a rapid increase in knowledge in this regard within the past decade; increasingly overlap syndromes and associations with other disease entities have been detected. In addition to general aspects, characteristics of anti-NMDAR-, anti-LGI1-, anti-GABAA and GABABR, anti-AMPAR-, anti-CASPR2-, anti-mGluR, anti-GlycinR-, anti-GAD, anti- DPPX- and anti-D2 R encephalitis and the anti-IgLON5 encephalopathy will be presented. © Georg Thieme Verlag KG Stuttgart · New York.

Significance of clonal rearrangements of lymphocyte antigen receptor genes on the prognosis of chronic enteropathy in 22 Shiba dogs.

PubMed

Ohmi, Aki; Ohno, Koichi; Uchida, Kazuyuki; Goto-Koshino, Yuko; Tomiyasu, Hirotaka; Kanemoto, Hideyuki; Fukushima, Kenjiro; Tsujimoto, Hajime

2017-09-29

Shiba dogs are predisposed to chronic enteropathy (CE) and have poorer prognosis than other dog breeds. The objective of this study was to investigate the significance of polymerase chain reaction for antigen receptor rearrangement (PARR) results on clinical findings and prognosis of Shiba dogs with CE. We retrospectively collected data on 22 Shiba dogs diagnosed as having CE. Fifty-nine percent of the dogs had clonality-positive results on PARR analysis. Furthermore, on histopathology, epitheliotropic behavior of small lymphocytes of the intestinal mucosa was observed significantly more frequently in dogs with clonal rearrangement of antigen receptor genes (P=0.027). The median overall survival time of clonality-positive dogs was 48 days (range, 4-239 days), compared to 271 days (range, 45-1,316+ days) in clonality-negative dogs. The median overall survival time of epitheliotropism-positive dogs was 76 days (range, 30-349 days) compared to 239 days (range, 4-1,316+ days) for epitheliotropism-negative dogs. Statistical analysis revealed that the clonality-positive result was associated with significantly shorter survival time (P=0.036). In contrast, presence or absence of epitheliotropism had no statistically significant effect on survival time (P=0.223). These cases might appropriately be diagnosed as small T-cell intestinal lymphoma; there are some common clinical and pathogenic features with human enteropathy-associated T-cell lymphoma type 2. The pathogenesis and poor prognosis for Shiba dogs with CE seem to be associated with this type of lymphoma, although further investigation is warranted.

Predicting post-vaccination autoimmunity: who might be at risk?

PubMed

Soriano, Alessandra; Nesher, Gideon; Shoenfeld, Yehuda

2015-02-01

Vaccinations have been used as an essential tool in the fight against infectious diseases, and succeeded in improving public health. However, adverse effects, including autoimmune conditions may occur following vaccinations (autoimmune/inflammatory syndrome induced by adjuvants--ASIA syndrome). It has been postulated that autoimmunity could be triggered or enhanced by the vaccine immunogen contents, as well as by adjuvants, which are used to increase the immune reaction to the immunogen. Fortunately, vaccination-related ASIA is uncommon. Yet, by defining individuals at risk we may further limit the number of individuals developing post-vaccination ASIA. In this perspective we defined four groups of individuals who might be susceptible to develop vaccination-induced ASIA: patients with prior post-vaccination autoimmune phenomena, patients with a medical history of autoimmunity, patients with a history of allergic reactions, and individuals who are prone to develop autoimmunity (having a family history of autoimmune diseases; asymptomatic carriers of autoantibodies; carrying certain genetic profiles, etc.). Copyright © 2014 Elsevier Ltd. All rights reserved.

Autoimmune Abnormalities of Postpartum Thyroid Diseases

PubMed Central

Di Bari, Flavia; Granese, Roberta; Le Donne, Maria; Vita, Roberto; Benvenga, Salvatore

2017-01-01

The year following parturition is a critical time for the de novo appearance or exacerbation of autoimmune diseases, including autoimmune thyroid disease. The vast majority of postpartum thyroid disease consists of postpartum thyroiditis (PPT) and the minority by Graves’ disease and non-autoimmune thyroiditis. PPT has a worldwide prevalence ranging from 1 to 22% and averaging 5% based on a review published in 2012. Several factors confer risk for the development of PPT. Typically, the clinical course of PPT is characterized by three phases: thyrotoxic, hypothyroid, and euthyroid phase. Approximately half of PPT women will have permanent hypothyroidism. The best humoral marker for predictivity, already during the first trimester of gestation, is considered positivity for thyroperoxidase autoantibodies (TPOAb), though only one-third to half of such TPOAb-positive pregnant women will develop PPT. Nutraceuticals (such as selenium) or omega-3-fatty acid supplements seem to have a role in prevention of PPT. In a recent study on pregnant women with stable dietary habits, we found that the fish consumers had lower rates of positivity (and lower serum levels) of both TPOAb and thyroglobulin Ab compared to meat eaters. Finally, we remind the reader of other diseases that can be observed in the postpartum period, either autoimmune or non-autoimmune, thyroid or non-thyroid. PMID:28751877

Autoimmune Encephalitis Following Bone Marrow Transplantation.

PubMed

Rathore, Geetanjali S; Leung, Kathryn S; Muscal, Eyal

2015-09-01

Neurological complications, especially encephalopathy and seizures, are commonly seen in bone marrow transplant patients. Infections, chemotoxicity, graft versus host disease, or secondary central nervous system malignancies are the most common underlying etiologies. There is increased awareness that autoimmune encephalitis may cause neurological dysfunction in immunocompetent children. The potential role of such a mechanism in children undergoing bone marrow transplantation is unknown. We report a boy who developed autoimmune encephalitis with voltage-gated potassium channel-associated and thyroid autoantibodies subsequent to transplantation. A 7-year-old boy presented with a change in behavior, poor attention, cognitive deficits, and abnormal movements 15 months after undergoing transplantation for idiopathic aplastic anemia. He had clinical and subclinical seizures and brain magnetic resonance imaging hyperintensities bilaterally in the uncal regions. His evaluation revealed high titers of voltage-gated potassium channel, leucine-rich glioma-inactivated 1 protein, and thyroglobulin antibodies suggestive of autoimmune limbic encephalitis. He showed significant improvement in behavior and neuropsychological testing and has remained seizure-free on levetiracetam after immunotherapy with corticosteroids and intravenous immunoglobulin. Systemic autoimmune manifestations in bone marrow transplant patients have been well-documented, but autoimmune encephalitis after transplantation has yet to be described in children. Copyright © 2015 Elsevier Inc. All rights reserved.

Recurrent protein-losing enteropathy and tricuspid valve insufficiency in a transplanted heart: a causal relationship?

PubMed

Aggarwal, Sanjeev; Delius, Ralph E; Walters, Henry L; L'Ecuyer, Thomas J

2012-01-01

This case report describes a toddler who developed a protein-losing enteropathy (PLE) 4 years after orthotopic heart transplantation (OHT). He was born with a hypoplastic left heart syndrome for which he underwent a successful Norwood procedure, a Hemi-Fontan palliation, and a Fontan palliation at 18 months of age. Fifteen months following the Fontan operation, he developed a PLE and Fontan failure requiring OHT. Four years after OHT, he developed a severe tricuspid regurgitation and a PLE. His PLE improved after tricuspid valve replacement. It is now 2 years since his tricuspid valve replacement and he remains clinically free of ascites and peripheral edema with a normal serum albumin level. His prosthetic tricuspid valve is functioning normally. © 2011 Wiley Periodicals, Inc.

Intraocular inflammation in autoimmune diseases.

PubMed

Pras, Eran; Neumann, Ron; Zandman-Goddard, Gisele; Levy, Yair; Assia, Ehud I; Shoenfeld, Yehuda; Langevitz, Pnina

2004-12-01

The uveal tract represents the vascular organ of the eye. In addition to providing most of the blood supply to the intraocular structures, it acts as a conduit for immune cells, particularly lymphocytes, to enter the eye. Consequently, the uveal tract is represented in many intraocular inflammatory processes. Uveitis is probably a misnomer unless antigens within the uvea are the direct targets of the inflammatory process. A better term of the condition is "intraocular inflammation" (IOI). To review the presence of IOI in autoimmune diseases, the immunopathogenic mechanisms leading to disease, and treatment. We reviewed the English medical literature by using MEDLINE (1984-2003) employing the terms "uveitis," "intraocular inflammation," and "autoimmune diseases." An underlying autoimmune disease was identified in up to 40% of patients with IOI, and included spondyloarthropathies, Behcets disease, sarcoidosis, juvenile chronic arthritis, Vogt-Koyanagi-Harada syndrome (an inflammatory syndrome including uveitis with dermatologic and neurologic manifestations), immune recovery syndrome, and uveitis with tubulointerstitial disease. The immunopathogenesis of IOI involves enhanced T-cell response. Recently, guidelines for the use of immunosuppressive drugs for inflammatory eye disease were established and include: corticosteroids, azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, cyclophosphamide, and chlorambucil. New therapies with limited experience include the tumor necrosis factor alpha inhibitors, interferon alfa, monoclonal antibodies against lymphocyte surface antigens, intravenous immunoglobulin (IVIG), and the intraocular delivery of immunosuppressive agents. An underlying autoimmune disease was identified in up to 40% of patients with IOI. Immunosuppressive drugs, biologic agents, and IVIG are employed for the treatment of IOI in autoimmune diseases.

Transplantation of autoimmune regulator-encoding bone marrow cells delays the onset of experimental autoimmune encephalomyelitis.

PubMed

Ko, Hyun-Ja; Kinkel, Sarah A; Hubert, François-Xavier; Nasa, Zeyad; Chan, James; Siatskas, Christopher; Hirubalan, Premila; Toh, Ban-Hock; Scott, Hamish S; Alderuccio, Frank

2010-12-01

The autoimmune regulator (AIRE) promotes "promiscuous" expression of tissue-restricted antigens (TRA) in thymic medullary epithelial cells to facilitate thymic deletion of autoreactive T-cells. Here, we show that AIRE-deficient mice showed an earlier development of myelin oligonucleotide glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). To determine the outcome of ectopic Aire expression, we used a retroviral transduction system to over-express Aire in vitro, in cell lines and in bone marrow (BM). In the cell lines that included those of thymic medullary and dendritic cell origin, ectopically expressed Aire variably promoted expression of TRA including Mog and Ins2 (proII) autoantigens associated, respectively, with the autoimmune diseases multiple sclerosis and type 1 diabetes. BM chimeras generated from BM transduced with a retrovirus encoding Aire displayed elevated levels of Mog and Ins2 expression in thymus and spleen. Following induction of EAE with MOG(35-55), transplanted mice displayed significant delay in the onset of EAE compared with control mice. To our knowledge, this is the first example showing that in vivo ectopic expression of AIRE can modulate TRA expression and alter autoimmune disease development. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cellular immunity and immunopathology in autoimmune Addison's disease.

PubMed

Bratland, Eirik; Husebye, Eystein S

2011-04-10

Autoimmune adrenocortical failure, or Addison's disease, is a prototypical organ-specific autoimmune disorder. In common with related autoimmune endocrinopathies, Addison's disease is only manageable to a certain extent with replacement therapy being the only treatment option. Unfortunately, the available therapy does not restore the physiological hormone levels and biorhythm. The key to progress in treating and preventing autoimmune Addison's disease lies in improving our understanding of the predisposing factors, the mechanisms responsible for the progression of the disease, and the interactions between adrenal antigens and effector cells and molecules of the immune system. The aim of the present review is to summarize the current knowledge on the role of T cells and cellular immunity in the pathogenesis of autoimmune Addison's disease. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Inheritable and sporadic non-autoimmune hyperthyroidism.

PubMed

Ferraz, Carolina; Paschke, Ralf

2017-03-01

Hyperthyroidism is a clinical state that results from high thyroid hormone levels which has multiple etiologies, manifestations, and potential therapies. Excluding the autoimmune Graves disease, autonomic adenomas account for the most import cause of non-autoimmune hyperthyroidism. Activating germline mutations of the TSH receptor are rare etiologies for hyperthyroidism. They can be inherited in an autosomal dominant manner (familial or hereditary, FNAH), or may occur sporadically as a de novo condition, also called: persistent sporadic congenital non-autoimmune hyperthyroidism (PSNAH). These three conditions: autonomic adenoma, FNAH and PSNAH constitute the inheritable and sporadic non-autoimmune hyperthyroidism. Particularities in epidemiology, etiology, molecular and clinical aspects of these three entities will be discussed in this review in order to guide to an accurate diagnosis allowing among others genetic counseling and presymptomatic diagnosis for the affected families. The optimal treatment based on the right diagnosis will avoid consequences of a persistent or relapsing hyperthyroidism. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Autoimmunity in endocrine diseases.

PubMed

Rose, N R; Burek, C L

1982-01-01

The realization that autoimmunity underlies many endocrine disorders of previously unknown etiology has greatly broadened our understanding of the pathogenesis of these diseases. It has provided new explanations for their heredity and their association with particular HLA haplotypes. It has also offered new tools for diagnosing these diseases as well as monitoring their course or predicting their outcome. Finally, establishing the autoimmune basis of these diseases offers new potential for their treatment. The next quarter century of research into immunologic aspects of endocrine diseases promises to be as fruitful as the last.

AAV-mediated pancreatic overexpression of Igf1 counteracts progression to autoimmune diabetes in mice.

PubMed

Mallol, Cristina; Casana, Estefania; Jimenez, Veronica; Casellas, Alba; Haurigot, Virginia; Jambrina, Claudia; Sacristan, Victor; Morró, Meritxell; Agudo, Judith; Vilà, Laia; Bosch, Fatima

2017-07-01

Type 1 diabetes is characterized by autoimmune destruction of β-cells leading to severe insulin deficiency. Although many improvements have been made in recent years, exogenous insulin therapy is still imperfect; new therapeutic approaches, focusing on preserving/expanding β-cell mass and/or blocking the autoimmune process that destroys islets, should be developed. The main objective of this work was to test in non-obese diabetic (NOD) mice, which spontaneously develop autoimmune diabetes, the effects of local expression of Insulin-like growth factor 1 (IGF1), a potent mitogenic and pro-survival factor for β-cells with immunomodulatory properties. Transgenic NOD mice overexpressing IGF1 specifically in β-cells (NOD-IGF1) were generated and phenotyped. In addition, miRT-containing, IGF1-encoding adeno-associated viruses (AAV) of serotype 8 (AAV8-IGF1-dmiRT) were produced and administered to 4- or 11-week-old non-transgenic NOD females through intraductal delivery. Several histological, immunological, and metabolic parameters were measured to monitor disease over a period of 28-30 weeks. In transgenic mice, local IGF1 expression led to long-term suppression of diabetes onset and robust protection of β-cell mass from the autoimmune insult. AAV-mediated pancreatic-specific overexpression of IGF1 in adult animals also dramatically reduced diabetes incidence, both when vectors were delivered before pathology onset or once insulitis was established. Transgenic NOD-IGF1 and AAV8-IGF1-dmiRT-treated NOD animals had much less islet infiltration than controls, preserved β-cell mass, and normal insulinemia. Transgenic and AAV-treated islets showed less expression of antigen-presenting molecules, inflammatory cytokines, and chemokines important for tissue-specific homing of effector T cells, suggesting IGF1 modulated islet autoimmunity in NOD mice. Local expression of Igf1 by AAV-mediated gene transfer counteracts progression to diabetes in NOD mice. This study suggests a

Severe systemic autoimmune disease associated with Epstein-Barr virus infection.

PubMed

Sevilla, Julián; del Carmen Escudero, Maria; Jiménez, Raquel; González-Vicent, Marta; Manzanares, Javier; García-Novo, Dolores; Madero, Luis

2004-12-01

Infection with Epstein-Barr virus (EBV) has been associated with different autoimmune manifestations. The authors describe a girl who developed a severe systemic autoimmune disease with severe autoimmune hemolytic anemia, mild autoimmune thrombopenia, antineutrophil antibodies, and fatal autoimmune hepatitis after EBV infection. Despite immunosuppressive treatment and ultimately liver transplantation, this patient could not overcome her clinical condition and died. The etiopathogenesis of this complex disease and the association with EBV infection is discussed.

Cocaine/levamisole-associated autoimmune syndrome: a disease of neutrophil-mediated autoimmunity.

PubMed

Cascio, Michael J; Jen, Kuang-Yu

2018-01-01

Levamisole was previously used for its immunomodulatory properties to treat rheumatoid arthritis and some cancers. However, because of serious side-effects, it was taken off the market in the United States. Recently, levamisole has reemerged as a popular cocaine adulterant. Some individuals who consume levamisole-adulterated cocaine can develop a life-threatening autoimmune syndrome. In this review, the medical consequences of levamisole exposure and postulated mechanisms by which levamisole induces these adverse effects are discussed. Although agranulocytosis and cutaneous vasculitis are the major findings in patients who develop cocaine/levamisole-associated autoimmune syndrome (CLAAS), more recent experience indicates that other organ systems can be involved as well. Current studies point to neutrophil activation and neutrophil extracellular trap formation with subsequent antineutrophil cytoplasmic antibody-mediated tissue injury as a possible mechanism of CLAAS. In the past decade, the detrimental effects of levamisole have reemerged because of its popularity as a cocaine adulterant. Although infrequent, some individuals develop a systemic autoimmune syndrome characterized by immune-mediated agranulocytosis and antineutrophil cytoplasmic antibody-mediated vasculitis. Mechanistically, neutrophil antigens appear to be a major player in inducing CLAAS. Prompt cessation of levamisole exposure is key to treatment, although relapses are frequent because of the addictive effects of cocaine and the high prevalence of levamisole within the cocaine supply.

High salt intake does not exacerbate murine autoimmune thyroiditis

PubMed Central

Kolypetri, P; Randell, E; Van Vliet, B N; Carayanniotis, G

2014-01-01

Recent studies have shown that high salt (HS) intake exacerbates experimental autoimmune encephalomyelitis and have raised the possibility that a HS diet may comprise a risk factor for autoimmune diseases in general. In this report, we have examined whether a HS diet regimen could exacerbate murine autoimmune thyroiditis, including spontaneous autoimmune thyroiditis (SAT) in non-obese diabetic (NOD.H2h4) mice, experimental autoimmune thyroiditis (EAT) in C57BL/6J mice challenged with thyroglobulin (Tg) and EAT in CBA/J mice challenged with the Tg peptide (2549–2560). The physiological impact of HS intake was confirmed by enhanced water consumption and suppressed aldosterone levels in all strains. However, the HS treatment failed to significantly affect the incidence and severity of SAT or EAT or Tg-specific immunoglobulin (Ig)G levels, relative to control mice maintained on a normal salt diet. In three experimental models, these data demonstrate that HS intake does not exacerbate autoimmune thyroiditis, indicating that a HS diet is not a risk factor for all autoimmune diseases. PMID:24528002

Is Multiple Sclerosis an Autoimmune Disease?

PubMed Central

Wootla, Bharath; Eriguchi, Makoto; Rodriguez, Moses

2012-01-01

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

Autoimmunity and primary immunodeficiency: two sides of the same coin?

PubMed

Schmidt, Reinhold E; Grimbacher, Bodo; Witte, Torsten

2017-12-19

Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions; however, increased understanding of the complex immune regulatory and signalling mechanisms involved, coupled with the application of genetic analysis, is revealing the complex relationships between primary immunodeficiency syndromes and autoimmune diseases. Single-gene defects can cause rare diseases that predominantly present with autoimmune symptoms. Such genetic defects also predispose individuals to recurrent infections (a hallmark of immunodeficiency) and can cause primary immunodeficiencies, which can also lead to immune dysregulation and autoimmunity. Moreover, risk factors for polygenic rheumatic diseases often exist in the same genes as the mutations that give rise to primary immunodeficiency syndromes. In this Review, various primary immunodeficiency syndromes are presented, along with their pathogenetic mechanisms and relationship to autoimmune diseases, in an effort to increase awareness of immunodeficiencies that occur concurrently with autoimmune diseases and to highlight the need to initiate appropriate genetic tests. The growing knowledge of various genetically determined pathologic mechanisms in patients with immunodeficiencies who have autoimmune symptoms opens up new avenues for personalized molecular therapies that could potentially treat immunodeficiency and autoimmunity at the same time, and that could be further explored in the context of autoimmune rheumatic diseases.

A Longitudinal Follow-up of Autoimmune Polyendocrine Syndrome Type 1.

PubMed

Bruserud, Øyvind; Oftedal, Bergithe E; Landegren, Nils; Erichsen, Martina M; Bratland, Eirik; Lima, Kari; Jørgensen, Anders P; Myhre, Anne G; Svartberg, Johan; Fougner, Kristian J; Bakke, Åsne; Nedrebø, Bjørn G; Mella, Bjarne; Breivik, Lars; Viken, Marte K; Knappskog, Per M; Marthinussen, Mihaela C; Løvås, Kristian; Kämpe, Olle; Wolff, Anette B; Husebye, Eystein S

2016-08-01

Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insufficiency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse. To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator (AIRE) mutations during extended follow-up (1996-2016). All known Norwegian patients with APS1. Fifty-two patients from 34 families were identified. The majority presented with one of the major disease components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent components. With age, most patients presented three to five disease manifestations, although some had milder phenotypes diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were deceased siblings with a high probability of undisclosed APS1. All except three had interferon-ω) autoantibodies, and all had organ-specific autoantibodies. The most common AIRE mutation was c.967_979del13, found in homozygosity in 15 patients. A mild phenotype was associated with the splice mutation c.879+1G>A. Primary adrenocortical insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes. Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon-ω) and AIRE sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured follow-up should be performed in a specialized center.

Autoimmune thyrotoxicosis: diagnostic challenges.

PubMed

Ponto, Katharina A; Kahaly, George J

2012-09-01

Autoimmune thyrotoxicosis or Graves' disease (GD) is the most common cause of hyperthyroidism in the United States (full text available online: http://education.amjmed.com/pp1/249). GD occurs more often in women (ratio 5:1) and has a population prevalence of 1-2%. A genetic determinant to the susceptibility to GD is suspected because of familial clustering of the disease, a high sibling recurrence risk, and the familial occurrence of thyroid autoantibodies. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens. Stimulatory autoantibodies in GD activate the TSHR leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders. Copyright © 2012. Published by Elsevier Inc.

Autoimmune mechanisms in myasthenia gravis.

PubMed

Cavalcante, Paola; Bernasconi, Pia; Mantegazza, Renato

2012-10-01

This article reviews recent findings on factors and mechanisms implicated in the pathogenesis of myasthenia gravis and briefly summarizes data on therapies acting at various stages of the autoimmune process. Data published over the last year promise to improve understanding of pathogenic mechanisms underlying myasthenia gravis. Animal studies have at last shown that antimuscle-specific kinase (MuSK) autoantibodies, like antiacetylcholine receptor (AChR) autoantibodies, are myasthenogenic. A new autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), has been identified in variable proportions of otherwise seronegative patients. Anti-LRP4 antibodies may define a new myasthenia gravis subtype, supporting the concept that myasthenia gravis is not a single disease entity, and that different subtypes can differ in aetiology. Genetic and environmental factors are implicated in myasthenia gravis. The finding of persisting viral infection in the thymus of AChR-myasthenia gravis patients, combined with data on chronic inflammation, suggest that pathogens may favour intrathymic AChR-specific autosensitization and maintenance of autoimmunity in genetically susceptible individuals. Defective immunoregulatory mechanisms, involving pathogenic Th17 and regulatory T cells, contribute to tolerance loss and perpetuation of the autoimmune response in myasthenia gravis patients. The recent identification of mechanisms initiating and perpetuating autoimmunity in myasthenia gravis may stimulate the development of more effective therapies.

“Autoimmune Epilepsy”: Encephalitis With Autoantibodies for Epileptologists

PubMed Central

Bien, Christian G.; Holtkamp, Martin

2017-01-01

Autoimmune encephalitides may account for epilepsies of so far unknown cause. These “autoimmune epilepsies” may respond well to immunotherapy. More than a dozen autoantibodies have been found with this constellation; therefore, broad autoantibody testing of serum-CSF pairs offers the best diagnostic yield. Several particular features raise the suspicion of an autoimmune cause in otherwise unexplained seizure disorders. PMID:28684941

Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura.

PubMed

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

2015-10-01

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.

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

Autoimmune hepatitis

MedlinePlus

... and Liver Disease. 10th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 90. Pawlotsky J-M. Chronic viral and autoimmune hepatitis. In: Goldman L, ... Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 149. ... Updated by: Michael M. Phillips, MD, Clinical Professor of Medicine, The George ...

Autoimmune disease prevalence in a multiple sclerosis cohort in Argentina.

PubMed

Farez, Mauricio F; Balbuena Aguirre, María E; Varela, Francisco; Köhler, Alejandro A; Correale, Jorge

2014-01-01

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

Autoimmune Disease Prevalence in a Multiple Sclerosis Cohort in Argentina

PubMed Central

Farez, Mauricio F.; Balbuena Aguirre, María E.; Varela, Francisco; Köhler, Alejandro A.

2014-01-01

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

A candidate gene for autoimmune myasthenia gravis

PubMed Central

Landouré, Guida; Knight, Melanie A.; Stanescu, Horia; Taye, Addis A.; Shi, Yijun; Diallo, Oumarou; Johnson, Janel O.; Hernandez, Dena; Traynor, Bryan J.; Biesecker, Leslie G.; Elkahloun, Abdel; Rinaldi, Carlo; Vincent, Angela; Willcox, Nick; Kleta, Robert; Fischbeck, Kenneth H.

2012-01-01

Objective: We sought to identify a causative mutation in a previously reported kindred with parental consanguinity and 5 of 10 siblings with adult-onset autoimmune myasthenia gravis. Methods: We performed genome-wide homozygosity mapping, and sequenced all known genes in the one region of extended homozygosity. Quantitative and allele-specific reverse transcriptase PCR (RT-PCR) were performed on a candidate gene to determine the RNA expression level in affected siblings and controls and the relative abundance of the wild-type and mutant alleles in a heterozygote. Results: A region of shared homozygosity at chromosome 13q13.3–13q14.11 was found in 4 affected siblings and 1 unaffected sibling. A homozygous single nucleotide variant was found in the 3′-untranslated region of the ecto-NADH oxidase 1 gene (ENOX1). No other variants likely to be pathogenic were found in genes in this region or elsewhere. The ENOX1 sequence variant was not found in 764 controls. Quantitative RT-PCR showed that expression of ENOX1 decreased to about 20% of normal levels in lymphoblastoid cells from individuals homozygous for the variant and to about 50% in 2 unaffected heterozygotes. Allele-specific RT-PCR showed a 55%–60% reduction in the level of the variant transcript in heterozygous cells due to reduced mRNA stability. Conclusion: These results indicate that this sequence variant in ENOX1 may contribute to the familial autoimmune myasthenia in these patients. PMID:22744667

Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders.

PubMed

Ordookhani, Arash; Burman, Kenneth D

2017-04-01

There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted.

Adoptive cell transfer in autoimmune hepatitis.

PubMed

Czaja, Albert J

2015-06-01

Adoptive cell transfer is an intervention in which autologous immune cells that have been expanded ex vivo are re-introduced to mitigate a pathological process. Tregs, mesenchymal stromal cells, dendritic cells, macrophages and myeloid-derived suppressor cells have been transferred in diverse immune-mediated diseases, and Tregs have been the focus of investigations in autoimmune hepatitis. Transferred Tregs have improved histological findings in animal models of autoimmune hepatitis and autoimmune cholangitis. Key challenges relate to discrepant findings among studies, phenotypic instability of the transferred population, uncertain side effects and possible need for staged therapy involving anti-inflammatory drugs. Future investigations must resolve issues about the purification, durability and safety of these cells and consider alternative populations if necessary.

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. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

The Role of Gluten in Celiac Disease and Type 1 Diabetes.

PubMed

Serena, Gloria; Camhi, Stephanie; Sturgeon, Craig; Yan, Shu; Fasano, Alessio

2015-08-26

Celiac disease (CD) and type 1 diabetes (T1D) are autoimmune conditions in which dietary gluten has been proven or suggested to play a pathogenic role. In CD; gluten is established as the instigator of autoimmunity; the autoimmune process is halted by removing gluten from the diet; which allows for resolution of celiac autoimmune enteropathy and subsequent normalization of serological markers of the disease. However; an analogous causative agent has not yet been identified for T1D. Nevertheless; the role of dietary gluten in development of T1D and the potentially beneficial effect of removing gluten from the diet of patients with T1D are still debated. In this review; we discuss the comorbid occurrence of CD and T1D and explore current evidences for the specific role of gluten in both conditions; specifically focusing on current evidence on the effect of gluten on the immune system and the gut microbiota.

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

Tick-borne diseases and autoimmunity: A comprehensive review.

PubMed

Rodríguez, Yhojan; Rojas, Manuel; Gershwin, M Eric; Anaya, Juan-Manuel

2018-03-01

Tick-borne diseases (TBDs) are emerging and reemerging diseases transmitted by ticks, which portray wide heterogeneity and global distribution. TBDs may present acute clinical pictures that resemble those of autoimmune diseases (i.e., musculoskeletal symptoms, cutaneous involvement, neurologic impairment, renal failure, etc.), and in some cases infection is considered a triggering factor for autoimmunity (e.g., rheumatoid arthritis, autoimmune thyroid disease, vasculitides). The clinician should consider TBDs among the differential diagnoses when approaching autoimmune-like signs in areas of tick infestation. Epidemiological setting (e.g., endemic areas, seasons) and an accurate diagnostic approach (i.e., clinical history, physical examination and laboratory tests) are necessary to confirm TBDs. Further, control and prevention of TBDs is warranted. Research in the fields of ticks microbiome and vaccination (i.e., wildlife and humans) are ahead to control vector transmission and bacterial infection. This review offers a comprehensive update on TBDs and their relationship with autoimmunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protothecal enteritis as a cause of protein-losing enteropathy in a bull.

PubMed

Osterstock, Jason B; Mansell, Joanne L; Roussel, Allen J

2005-11-01

Prototheca spp are achlorophyllic saprophytic algae found in wastewater, sewage, agricultural waste, and possibly elsewhere in the environment. Infections with these organisms have been reported in cattle, humans, and dogs; affected cattle commonly develop mastitis. A 5-year-old Brahman-cross bull was evaluated because of a history of diarrhea and weight loss. The history and physical examination and clinicopathologic findings were similar to those associated with granulomatous enteritis caused by Mycobacterium avium subsp paratuberculosis (Johne's disease), which is the most common protein-losing enteropathy of cattle. However, diagnostic tests for paratuberculosis yielded negative results. Biopsy specimens from the ileum, jejunum, and ileocecal lymph node were collected for histologic examination and preparation of tissue impression smears; Prototheca-like organisms were identified. Because of the poor prognosis associated with this infection and the lack of safe and economical therapeutic agents for cattle, the owner decided to euthanatize the bull. Infection with Prototheca organisms was confirmed postmortem. As this case illustrates, protothecosis may be a cause of granulomatous enteritis in cattle.

Barriers to Immunizations and Strategies to Enhance Immunization Rates in Adults with Autoimmune Inflammatory Diseases.

PubMed

Kirchner, Elizabeth; Ruffing, Victoria

2017-02-01

For as long as there have been immunizations, there have been barriers to them. Immunization rates in the United States are below target. Rheumatologists and rheumatology practitioners need to understand the issues of immunizations in patients with autoimmune inflammatory disease to identify and overcome barriers to immunization. Several strategies for overcoming these barriers are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Autoimmune vitiligo in rheumatic disease in the mestizo Mexican population.

PubMed

Avalos-Díaz, Esperanza; Pérez-Pérez, Elena; Rodríguez-Rodríguez, Mayra; Pacheco-Tovar, María-Guadalupe; Herrera-Esparza, Rafael

2016-08-01

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.

Targeting the Notch signaling pathway in autoimmune diseases.

PubMed

Ma, Daoxin; Zhu, Yuanchao; Ji, Chunyan; Hou, Ming

2010-05-01

The Notch signaling pathway regulates a variety of processes and has been linked to diverse effects. Aberrant Notch function is important in several disorders. Pre-clinical studies have suggested that inhibition of Notch is an attractive approach to treat hematologic and solid malignancies. Many patients with refractory autoimmune diseases respond poorly to therapy and have significant morbidity and the treatment is highly toxic, so more effective therapies for autoimmune diseases are being examined. The role of the Notch pathway and therapeutic strategies targeting it in many illnesses, especially autoimmune diseases. The Notch pathway has unique and attractive advantages for targeting. Targeting it has already been trialed in many experiments, which may show better efficacy and fewer side effects compared with classical drugs for the treatment. Targeting Notch might provide etiological rather than symptomatic treatment. Various methods targeting the Notch pathway have been under investigation. Rational targeting of the Notch signaling pathway in cancer and some autoimmune diseases has proven to be successful. Classical drugs for the treatment of autoimmune diseases are inefficient and toxic to some extent, and targeting the Notch pathway is a promising therapeutic concept. However, there are still many questions about targeting Notch in autoimmune diseases, and further investigation will be needed.

Same-sex marriage, autoimmune thyroid gland dysfunction and other autoimmune diseases in Denmark 1989-2008.

PubMed

Frisch, Morten; Nielsen, Nete Munk; Pedersen, Bo Vestergaard

2014-01-01

Autoimmune diseases have been little studied in gay men and lesbians. We followed 4.4 million Danes, including 9,615 same-sex married (SSM) persons, for 47 autoimmune diseases in the National Patient Registry between 1989 and 2008. Poisson regression analyses provided first hospitalization rate ratios (RRs) comparing rates between SSM individuals and persons in other marital status categories. SSM individuals experienced no unusual overall risk of autoimmune diseases. However, the risk of autoimmune thyroid dysfunction was increased, notably Hashimoto's thyroiditis (women(SSM), RR = 2.92; 95% confidence interval (CI) 1.74-4.55) and Graves' disease (men(SSM), RR = 1.88; 95% CI 1.08-3.01). There was also an excess of primary biliary cirrhosis (women(SSM), RR = 4.09; 95% CI 1.01-10.7), and of psoriasis (men(SSM), RR = 2.48; 95% CI 1.77-3.36), rheumatic fever (men(SSM), RR = 7.55; 95% CI 1.87-19.8), myasthenia gravis (men(SSM), RR = 5.51; 95% CI 1.36-14.4), localized scleroderma (men(SSM), RR = 7.16; 95% CI 1.18-22.6) and pemphigoid (men(SSM), RR = 6.56; 95% CI 1.08-20.6), while Dupuytren's contracture was reduced (men(SSM), RR = 0.64; 95% CI 0.39-0.99). The excess of psoriasis was restricted to same-sex married men with HIV/AIDS (men(SSM), RR = 10.5; 95% CI 6.44-15.9), whereas Graves' disease occurred in excess only among same-sex married men without HIV/AIDS (men(SSM), RR = 1.99; 95% CI 1.12-3.22). Lesbians and immunologically competent gay men in same-sex marriage face no unusual overall risk of autoimmune diseases. However, the observed increased risk of thyroid dysfunction in these lesbians and gay men deserves further study.

Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study.

PubMed

Grönlund, O; Herweijer, E; Sundström, K; Arnheim-Dahlström, L

2016-12-01

To assess whether quadrivalent human papillomavirus (qHPV) vaccination is associated with increased incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease. This register-based open cohort study included all girls and women between 10 and 30 years of age in Sweden in 2006-2012 diagnosed with at least one of 49 prespecified autoimmune diseases (n = 70 265). Incidence rate ratios were estimated for new-onset autoimmune disease within 180 days of qHPV vaccination using Poisson regression adjusting for, country of birth, parental country of birth, parental income and parental education. A total of 70 265 girls and women had at least one of the 49 predefined autoimmune diseases; 16% of these individuals received at least one dose of qHPV vaccine. In unvaccinated girls and women, 5428 new-onset autoimmune diseases were observed during 245 807 person-years at a rate of 22.1 (95% CI 21.5-22.7) new events per 1000 person-years. In vaccinated girls and women, there were 124 new events during 7848 person-years at a rate of 15.8 (95% CI 13.2-18.8) per 1000 person-years. There was no increase in the incidence of new-onset autoimmune disease associated with qHPV vaccination during the risk period; on the contrary, we found a slightly reduced risk (incidence rate ratio 0.77, 95% CI 0.65-0.93). In this nationwide study, qHPV vaccination was not associated with increased incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease. © 2016 The Association for the Publication of the Journal of Internal Medicine.

Protein-losing Enteropathy Caused by Intestinal or Colonic Lymphangiectasia Complicated by Sporadic Lymphangioleiomyomatosis: A Report of Two Cases

PubMed Central

Nishino, Koichi; Yoshimi, Kaku; Shibuya, Tomoyoshi; Hayashi, Takuo; Mitani, Keiko; Kobayashi, Etsuko; Ichikawa, Masako; Asao, Tetsuhiko; Suzuki, Yohei; Sato, Tadashi; Shiota, Satomi; Kodama, Yuzo; Takahashi, Kazuhisa; Seyama, Kuniaki

2017-01-01

This report describes two patients with sporadic lymphangioleiomyomatosis complicated by protein-losing enteropathy (PLE). Imaging studies indicated retroperitoneal lymphangioleiomyomas and abnormalities of the adjacent digestive tract. Endoscopic mucosal biopsy revealed colonic lymphangiectasia in one patient; whereas the site in the other patient was intestinal. Treatment with sirolimus led to the complete resolution of PLE within several months; additionally, marked shrinkage was observed in the lymphangioleiomyomas of both cases. These findings suggest that colonic or intestinal lymphatic congestion due to neighboring lymphangioleiomyomas was the mechanism for the development of PLE. At the time of writing this report, the beneficial effect of sirolimus has lasted for more than 3 years. PMID:28420844

Protein-losing Enteropathy Caused by Intestinal or Colonic Lymphangiectasia Complicated by Sporadic Lymphangioleiomyomatosis: A Report of Two Cases.

PubMed

Nishino, Koichi; Yoshimi, Kaku; Shibuya, Tomoyoshi; Hayashi, Takuo; Mitani, Keiko; Kobayashi, Etsuko; Ichikawa, Masako; Asao, Tetsuhiko; Suzuki, Yohei; Sato, Tadashi; Shiota, Satomi; Kodama, Yuzo; Takahashi, Kazuhisa; Seyama, Kuniaki

2017-01-01

This report describes two patients with sporadic lymphangioleiomyomatosis complicated by protein-losing enteropathy (PLE). Imaging studies indicated retroperitoneal lymphangioleiomyomas and abnormalities of the adjacent digestive tract. Endoscopic mucosal biopsy revealed colonic lymphangiectasia in one patient; whereas the site in the other patient was intestinal. Treatment with sirolimus led to the complete resolution of PLE within several months; additionally, marked shrinkage was observed in the lymphangioleiomyomas of both cases. These findings suggest that colonic or intestinal lymphatic congestion due to neighboring lymphangioleiomyomas was the mechanism for the development of PLE. At the time of writing this report, the beneficial effect of sirolimus has lasted for more than 3 years.

Pregnancy and autoimmune connective tissue diseases

PubMed Central

Marder, Wendy; Littlejohn, Emily A

2016-01-01

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

[Oral diseases in auto-immune polyendocrine syndrome type 1].

PubMed

Proust-Lemoine, Emmanuelle; Guyot, Sylvie

2017-09-01

Auto-immune polyendocrine syndrome type 1 (APS1) also called Auto-immune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare monogenic childhood-onset auto-immune disease. This autosomal recessive disorder is caused by mutations in the auto-immune regulator (AIRE) gene, and leads to autoimmunity targeting peripheral tissues. There is a wide variability in clinical phenotypes in patients with APSI, with auto-immune endocrine and non-endocrine disorders, and chronic mucocutaneous candidiasis. These patients suffer from oral diseases such as dental enamel hypoplasia and candidiasis. Both are frequently described, and in recent series, enamel hypoplasia and candidiasis are even the most frequent components of APS1 together with hypoparathyroidism. Both often occur during childhood (before 5 years old for canrdidiasis, and before 15 years old for enamel hypoplasia). Oral candidiasis is recurrent all life long, could become resistant to azole antifungal after years of treatment, and be carcinogenic, leading to severe oral squamous cell carcinoma. Oral components of APS1 should be diagnosed and rigorously treated. Dental enamel hypoplasia and/or recurrent oral candidiasis in association with auto-immune diseases in a young child should prompt APS1 diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Autoimmune gastritis: histology phenotype and OLGA staging.

PubMed

Rugge, M; Fassan, M; Pizzi, M; Zorzetto, V; Maddalo, G; Realdon, S; De Bernard, M; Betterle, C; Cappellesso, R; Pennelli, G; de Boni, M; Farinati, F

2012-06-01

Among Western populations, the declining incidence of Helicobacter pylori infection coincides with a growing clinical impact of autoimmune gastritis. To describe the histological phenotype of autoimmune gastritis, also to test the prognostic impact of OLGA staging in the autoimmune setting. A single-institutional series (spanning the years 2003-2011) of 562 consecutive patients (M:F ratio: 1:3.7; mean age = 57.6 ± 14.4 years) with serologically confirmed autoimmune gastritis underwent histology review and OLGA staging. Helicobacter pylori infection was ascertained histologically in 44/562 cases (7.8%). Forty six biopsy sets (8.2%) featured OLGA stages III-IV; they included all four cases of incidental epithelial neoplasia (three intraepithelial and one invasive; three of these four cases had concomitant H. pylori infection). There were 230 (40.9%) and 139 (24.7%) cases, respectively, of linear and micro-nodular enterochromaffin-like cell hyperplasia; 19 (3.4%) type I carcinoids were detected. The series included 116 patients who underwent repeated endoscopy/biopsy sampling (mean time elapsing between the two procedures = 54 months; range 24-108). Paired histology showed a significant (P = 0.009) trend towards a stage progression [the stage increased in 25/116 cases (22%); it remained unchanged in 87/116 cases (75%)]. In autoimmune gastritis, the cancer risk is restricted to high-risk gastritis stages (III-IV), and is associated mainly with concomitant H. pylori infection. OLGA staging consistently depicts the time-dependent organic progression of the autoimmune disease and provides key information for secondary gastric cancer prevention strategies. © 2012 Blackwell Publishing Ltd.

Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders

PubMed Central

Ordookhani, Arash; Burman, Kenneth D.

2017-01-01

Context There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. Evidence Acquisition A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Results Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Conclusions Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted. PMID:29026409

A case of polyglandular autoimmune syndrome type III complicated with autoimmune hepatitis.

PubMed

Oki, Kenji; Yamane, Kiminori; Koide, Junko; Mandai, Koichi; Nakanishi, Shuhei; Fujikawa, Rumi; Kohno, Nobuoki

2006-10-01

A 58-year-old woman complaining of finger tremor was referred to our hospital. The diagnosis of Graves' disease was made based on increased free triiodothyronine (18.88 pg/ml) and free thyroxine (7.47 ng/dl), low TSH (<0.005 microIU/ml) and increased TSH receptor binding antibody activity (70.9%). Serum level of AST (62 U/l) and ALT (93 U/l) were increased and liver biopsy revealed linkage of adjacent portal areas by lymphoplasmacytic infiltrates and fibrosis with piecemeal necrosis. Although antinuclear antibody was negative, these findings indicated that she had autoimmune hepatitis (AIH) according to the criteria of the International Autoimmune Hepatitis Scoring System. Slowly progressive type 1 diabetes mellitus (DM) was confirmed by a diabetic response pattern due to 75 g-oral glucose tolerance test, and seropositivity towards anti-glutamic acid decarboxylase (725 U/ml) and islet cell (80 JDF Units) antibodies. This case exhibited an extremely rare combination of three different autoimmune diseases, including Graves' disease, slowly progressive type 1 DM and AIH, and had no known sensitive human leukocyte antigen (HLA) typing or haplotype for these disorders. Although it is common for patients with Graves' disease to exhibit abnormal liver function, it is important to make an accurate diagnosis of AIH because of this life-threatening disorder.

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.

Retinal phlebitis associated with autoimmune hemolytic anemia.

PubMed

Chew, Fiona L M; Tajunisah, Iqbal

2009-01-01

To describe a case of retinal phlebitis associated with autoimmune hemolytic anemia. Observational case report. A 44-year-old Indian man diagnosed with autoimmune hemolytic anemia presented with a 1-week history of blurred vision in both eyes. Fundus biomicroscopy revealed bilateral peripheral retinal venous sheathing and cellophane maculopathy. Fundus fluorescent angiogram showed bilateral late leakage from the peripheral venous arcades and submacular fluid accumulation. The retinal phlebitis resolved following a blood transfusion and administration of systemic steroids. Retinopathy associated with autoimmune hemolytic anemia is not well known. This is thought to be the first documentation of retinal phlebitis occurring in this condition.

Inflammatory Bowel Disease and the Risk of Autoimmune Diseases.

PubMed

Wilson, J Claire; Furlano, Raoul I; Jick, Susan S; Meier, Christoph R

2016-02-01

An increased risk of autoimmune disease has been reported in patients with inflammatory bowel disease [IBD]. Using data from the Clinical Practice Research Datalink [CPRD], this study set out to further examine this relationship. Patients with a first-time IBD diagnosis were randomly matched to an equal-sized IBD-free comparison group. Incidence rates for new-onset autoimmune diseases were estimated. A nested case-control analysis comprising IBD patients was conducted, using conditional logistic regression to assess whether IBD severity, duration, or treatment influences the risk of developing autoimmune diseases. During follow-up, 1069 IBD and 585 IBD-free patients developed an incident autoimmune disease. An increased incidence of autoimmune disease was observed in IBD patients (incidence rate [IR] 9.65, 95% confidence interval [CI] 9.09-10.24) compared with the non-IBD comparison group [IR 5.22, 95% CI 4.82-5.66]. In IBD patients, increased disease severity was associated with an increased risk of autoimmune disease development (odds ratio [OR] 1.62, 95% CI 1.28-2.05). Current antibiotic use was also associated with an increased risk [adjusted OR 1.72, 95% CI 1.07-2.78]. A reduced risk of incident autoimmune diseases was observed for current long-term users of aminosalicylates [adjusted OR 0.72, 95% CI 0.57-0.91]. Individuals with IBD had an increased risk of developing an autoimmune disease. Increased disease severity and current antibiotic use were associated with an increased relative risk of developing additional autoimmune diseases in IBD patients. Long-term current aminosalicylate use was associated with a reduced risk. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A Longitudinal Follow-up of Autoimmune Polyendocrine Syndrome Type 1

PubMed Central

Bruserud, Øyvind; Oftedal, Bergithe E.; Landegren, Nils; Erichsen, Martina M.; Bratland, Eirik; Lima, Kari; Jørgensen, Anders P.; Myhre, Anne G.; Svartberg, Johan; Fougner, Kristian J.; Bakke, Åsne; Nedrebø, Bjørn G.; Mella, Bjarne; Breivik, Lars; Viken, Marte K.; Knappskog, Per M.; Marthinussen, Mihaela C.; Løvås, Kristian; Kämpe, Olle; Wolff, Anette B.

2016-01-01

Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insufficiency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse. Objective: To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator (AIRE) mutations during extended follow-up (1996–2016). Patients: All known Norwegian patients with APS1. Results: Fifty-two patients from 34 families were identified. The majority presented with one of the major disease components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent components. With age, most patients presented three to five disease manifestations, although some had milder phenotypes diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were deceased siblings with a high probability of undisclosed APS1. All except three had interferon-ω) autoantibodies, and all had organ-specific autoantibodies. The most common AIRE mutation was c.967_979del13, found in homozygosity in 15 patients. A mild phenotype was associated with the splice mutation c.879+1G>A. Primary adrenocortical insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes. Conclusions: Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon-ω) and AIRE sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured follow-up should be performed in a specialized center. PMID:27253668

Autoimmune Channelopathies of the Nervous System

PubMed Central

Kleopa, Kleopas A

2011-01-01

Ion channels are complex transmembrane proteins that orchestrate the electrical signals necessary for normal function of excitable tissues, including the central nervous system, peripheral nerve, and both skeletal and cardiac muscle. Progress in molecular biology has allowed cloning and expression of genes that encode channel proteins, while comparable advances in biophysics, including patch-clamp electrophysiology and related techniques, have made the functional assessment of expressed proteins at the level of single channel molecules possible. The role of ion channel defects in the pathogenesis of numerous disorders has become increasingly apparent over the last two decades. Neurological channelopathies are frequently genetically determined but may also be acquired through autoimmune mechanisms. All of these autoimmune conditions can arise as paraneoplastic syndromes or independent from malignancies. The pathogenicity of autoantibodies to ion channels has been demonstrated in most of these conditions, and patients may respond well to immunotherapies that reduce the levels of the pathogenic autoantibodies. Autoimmune channelopathies may have a good prognosis, especially if diagnosed and treated early, and if they are non-paraneoplastic. This review focuses on clinical, pathophysiologic and therapeutic aspects of autoimmune ion channel disorders of the nervous system. PMID:22379460

The role of AIRE in human autoimmune disease.

PubMed

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

2011-01-01

The autoimmune regulator (AIRE) gene encodes a transcription factor involved in the presentation of tissue-restricted antigens during T-cell development in the thymus. Mutations of this gene lead to type 1 autoimmune polyglandular syndrome (APS-1), also termed autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, which is characterized by the clinical presentation of at least two of a triad of underlying disorders: Addison disease, hypoparathyroidism and chronic mucocutaneous candidiasis. This Review describes the process of positive and negative selection of developing T cells in the thymus and the role of AIRE as a regulator of peripheral antigen presentation. Furthermore, it addresses how mutations of this gene lead to the failure to eliminate autoreactive T cells, which can lead to clinical autoimmune syndromes.

Autoimmune hemolytic anemia in systemic lupus erythematosus at diagnosis: differences between pediatric and adult patients.

PubMed

Gormezano, N W S; Kern, D; Pereira, O L; Esteves, G C X; Sallum, A M E; Aikawa, N E; Pereira, R M R; Silva, C A; Bonfá, E

2017-04-01

Objective To determine the overall prevalence of autoimmune hemolytic anemia (AIHA), and to compare clinical and laboratory features in a large population of children and adult lupus patients at diagnosis. Methods This retrospective study evaluated the medical charts of 336 childhood-onset systemic lupus erythematosus (cSLE) and 1830 adult SLE (aSLE) patients followed in the same tertiary hospital. Demographic data, clinical features and disease activity were recorded. AIHA was defined according to the presence of anemia (hemoglobin <10 g/dL) and evidence of hemolysis (reticulocytosis and positive direct antiglobulin test (DAT)/Coombs test) at SLE diagnosis. Evans syndrome (ES) was defined by the combination of immune thrombocytopenia (platelet count <100,000/mm 3 ) and AIHA. Results The frequency of AIHA at diagnosis was significantly higher in cSLE patients compared to aSLE (49/336 (14%) vs 49/1830 (3%), p = 0.0001), with similar frequency of ES (3/336 (0.9%) vs 10/1830 (0.5%), p = 0.438). The median of hemoglobin levels was reduced in cSLE vs aSLE patients (8.3 (2.2-10) vs 9.5 (6.6-10) g/dL, p = 0.002) with a higher frequency of multiple hemorrhagic manifestations (41% vs 7%, p = 0.041) and erythrocyte transfusion due to bleeding (24% vs 5%, p = 0.025). cSLE patients also had more often constitutional involvement (84% vs 31%, p < 0.001), fever (65% vs 26%, p < 0.001), weight loss > 2 kg (39% vs 6%, p < 0.001), reticuloendothelial manifestations (48% vs 8%, p < 0.001), hepatomegaly (25% vs 2%, p < 0.001) and splenomegaly (21% vs 2%, p = 0.004). Other major organ involvements were common but with similar frequencies in cSLE and aSLE ( p > 0.05). Median systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) was comparable in cSLE and aSLE (p = 0.161). Conclusions We identified that AIHA was not a common condition in cSLE and aSLE, with distinct features characterized by a higher prevalence

The Potential Roles of Bisphenol A (BPA) Pathogenesis in Autoimmunity

PubMed Central

2014-01-01

Bisphenol A (BPA) is a monomer found in commonly used consumer plastic goods. Although much attention in recent years has been placed on BPA's impact as an endocrine disruptor, it also appears to activate many immune pathways involved in both autoimmune disease development and autoimmune reactivity provocation. The current scientific literature is void of research papers linking BPA directly to human or animal onset of autoimmunity. This paper explores the impact of BPA on immune reactivity and the potential roles these mechanisms may have on the development or provocation of autoimmune diseases. Potential mechanisms by which BPA may be a contributing risk factor to autoimmune disease development and progression include its impact on hyperprolactinemia, estrogenic immune signaling, cytochrome P450 enzyme disruption, immune signal transduction pathway alteration, cytokine polarization, aryl hydrocarbon activation of Th-17 receptors, molecular mimicry, macrophage activation, lipopolysaccharide activation, and immunoglobulin pathophysiology. In this paper a review of these known autoimmune triggering mechanisms will be correlated with BPA exposure, thereby suggesting that BPA has a role in the pathogenesis of autoimmunity. PMID:24804084

Membranoproliferative glomerulonephritis associated with autoimmune diseases.

PubMed

Zand, Ladan; Fervenza, Fernando C; Nasr, Samih H; Sethi, Sanjeev

2014-04-01

Membranoproliferative glomerulonephritis (MPGN) has been classified based on its pathogenesis into immune complex-mediated and complement-mediated MPGN. The immune complex-mediated type is secondary to chronic infections, autoimmune diseases or monoclonal gammopathy. There is a paucity of data on MPGN associated with autoimmune diseases. We reviewed the Mayo Clinic database over a 10-year period and identified 12 patients with MPGN associated with autoimmune diseases, after exclusion of systemic lupus erythematosus. The autoimmune diseases included rheumatoid arthritis, primary Sjögren's syndrome, undifferentiated connective tissue disease, primary sclerosing cholangitis and Graves' disease. Nine of the 12 patients were female, and the mean age was 57.9 years. C4 levels were decreased in nine of 12 patients tested. The serum creatinine at time of renal biopsy was 2.2 ± 1.0 mg/dl and the urinary protein was 2,850 ± 3,543 mg/24 h. Three patients required dialysis at the time of renal biopsy. Renal biopsy showed an MPGN in all cases, with features of cryoglobulins in six cases; immunoglobulin (Ig)M was the dominant Ig, and both subendothelial and mesangial electron dense deposits were noted. Median follow-up was 10.9 months. Serum creatinine and proteinuria improved to 1.6 ± 0.8 mg/dl and 428 ± 677 mg/24 h, respectively, except in 3 patients with end-stage renal disease. In summary, this study describes the clinical features, renal biopsy findings, laboratory evaluation, treatment and prognosis of MPGN associated with autoimmune diseases.

Eating Disorders, Autoimmune, and Autoinflammatory Disease.

PubMed

Zerwas, Stephanie; Larsen, Janne Tidselbak; Petersen, Liselotte; Thornton, Laura M; Quaranta, Michela; Koch, Susanne Vinkel; Pisetsky, David; Mortensen, Preben Bo; Bulik, Cynthia M

2017-12-01

Identifying factors associated with risk for eating disorders is important for clarifying etiology and for enhancing early detection of eating disorders in primary care. We hypothesized that autoimmune and autoinflammatory diseases would be associated with eating disorders in children and adolescents and that family history of these illnesses would be associated with eating disorders in probands. In this large, nationwide, population-based cohort study of all children and adolescents born in Denmark between 1989 and 2006 and managed until 2012, Danish medical registers captured all inpatient and outpatient diagnoses of eating disorders and autoimmune and autoinflammatory diseases. The study population included 930 977 individuals (48.7% girls). Cox proportional hazards regression models and logistic regression were applied to evaluate associations. We found significantly higher hazards of eating disorders for children and adolescents with autoimmune or autoinflammatory diseases: 36% higher hazard for anorexia nervosa, 73% for bulimia nervosa, and 72% for an eating disorder not otherwise specified. The association was particularly strong in boys. Parental autoimmune or autoinflammatory disease history was associated with significantly increased odds for anorexia nervosa (odds ratio [OR] = 1.13, confidence interval [CI] = 1.01-1.25), bulimia nervosa (OR = 1.29; CI = 1.08-1.55) and for an eating disorder not otherwise specified (OR = 1.27; CI = 1.13-1.44). Autoimmune and autoinflammatory diseases are associated with increased risk for eating disorders. Ultimately, understanding the role of immune system disturbance for the etiology and pathogenesis of eating disorders could point toward novel treatment targets. Copyright © 2017 by the American Academy of Pediatrics.

Autoimmune Neuromuscular Disorders

PubMed Central

Kraker, Jessica; Živković, Saša A

2011-01-01

Autoimmune neuromuscular disorders affecting peripheral nerves, neuromuscular junction or muscle have a wide clinical spectrum with diverse pathogenetic mechanisms. Peripheral nervous system may be targeted in the context of complex immune reactions involving different cytokines, antigen-presenting cells, B cells and different types of T cells. Various immunomodulating and cytotoxic treatments block proliferation or activation of immune cells by different mechanisms attempting to control the response of the immune system and limit target organ injury. Most treatment protocols for autoimmune neuromuscular disorders are based on the use of corticosteroids, intravenous immunoglobulins and plasmapheresis, with cytotoxic agents mostly used as steroid-sparing medications. More recently, development of specific monoclonal antibodies targeting individual cell types allowed a different approach targeting specific immune pathways, but these new treatments are also associated with various adverse effects and their long-term efficacy is still unknown. PMID:22379454

Nivolumab in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma

ClinicalTrials.gov

2018-04-27

Blastic Plasmacytoid Dendritic Cell Neoplasm; Hepatosplenic T-Cell Lymphoma; HTLV-1 Infection; NK-Cell Lymphoma, Unclassifiable; Primary Systemic Anaplastic Large Cell Lymphoma, ALK-Negative; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Enteropathy-Associated T-Cell Lymphoma; Recurrent Mycosis Fungoides; Refractory Adult T-Cell Leukemia/Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Enteropathy-Associated T-Cell Lymphoma; Refractory Mycosis Fungoides; Refractory Nasal Type Extranodal NK/T-Cell Lymphoma; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified

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

Can infections prevent or cure allergy and autoimmunity?

PubMed

Kamradt, Thomas

2005-06-01

Extract: In western countries the prevalence and incidence of allergic and autoimmune diseases have been increasing dramatically over the last 50 years. In the last two decades, significant progress has been made towards understanding the genetic basis for susceptibility to autoimmunity or allergy. Genetic factors, however, cannot explain abrupt changes in disease incidence. It is therefore likely that environmental factors, specifically environmental factors that have changed over the last two generations, are critical for the increasing incidence of allergies and autoimmune diseases. Traditionally, autoimmune diseases such as multiple sclerosis (MS), type I diabetes, or rheumatoid arthritis (RA) are believed to have resulted from aberrant immune response to pathogens. In contrast, the "hygiene hypothesis," first postulated some 20 years ago, proposes that a lack of infections, especially during early childhood, predisposes one to the aberrant immune responses against harmless foreign antigens that cause allergic diseases such as rhinitis, atopic dermatitis, and allergic asthma. Several lines of epidemiological, clinical and experimental research point to more complex connections, either protective or pathogenic, between infection, allergy and autoimmunity.

[Animal models of autoimmune prostatitis and their evaluation criteria].

PubMed

Shen, Jia-ming; Lu, Jin-chun; Yao, Bing

2016-03-01

Chronic prostatitis is a highly prevalent disease of unclear etiology. Researches show that autoimmune reaction is one cause of the problem. An effective animal model may help a lot to understand the pathogenesis and find proper diagnostic and therapeutic strategies of the disease. Currently used autoimmune prostatitis-related animal models include those of age-dependent spontaneous prostatitis, autoimmune regulator-dependent spontaneous prostatitis, self antigen-induced prostatitis, and steroid-induced prostatitis. Whether an animal model of autoimmune prostatitis is successfully established can be evaluated mainly from the five aspects: histology, morphology, specific antigens, inflammatory factors, and pain intensity.

Altered B cell signalling in autoimmunity

PubMed Central

Rawlings, David J.; Metzler, Genita; Wray-Dutra, Michelle; Jackson, Shaun W.

2017-01-01

Recent work has provided new insights into how altered B cell-intrinsic signals — through the B cell receptor (BCR) and key co-receptors — function together to promote the pathogenesis of autoimmunity. These combined signals affect B cells at two distinct stages: first, in the selection of the naive repertoire; and second, during extrafollicular or germinal centre activation responses. Thus, dysregulated signalling can lead to both an altered naive BCR repertoire and the generation of autoantibody-producing B cells. Strikingly, high-affinity autoantibodies predate and predict disease in several autoimmune disorders, including type 1 diabetes and systemic lupus erythematosus. This Review summarizes how, rather than being a downstream consequence of autoreactive T cell activation, dysregulated B cell signalling can function as a primary driver of many human autoimmune diseases. PMID:28393923

Psychiatric Autoimmunity: N-Methyl-D-Aspartate Receptor IgG and Beyond.

PubMed

Kruse, Jennifer L; Lapid, Maria I; Lennon, Vanda A; Klein, Christopher J; Toole, Orna O'; Pittock, Sean J; Strand, Edythe A; Frye, Mark A; McKeon, Andrew

2015-01-01

Descriptions of psychiatric autoimmunity beyond N-methyl-D-aspartate (NMDA) receptor encephalitis are sparse. To report the autoimmune psychiatric spectrum currently recognized in Mayo Clinic practice. Medical record review, testing of stored serum and cerebrospinal fluid for IgGs reactive with synaptic receptors and ion channels, neuronal nuclear and cytoplasmic antigens (including glutamic acid decarboxylase 65-kDa isoform) and case-control comparison were conducted. Patients were categorized into group 1, all adult psychiatric inpatients tested for neural autoantibodies (2002-2011; n = 213), and group 2, all Mayo NMDA receptor IgG-positive patients (2009-2013; n = 13); healthy control subjects were also included (n = 173). In group 1, at least 1 serum autoantibody (but not NMDA receptor IgG) was detected in 36 of 213 psychiatric inpatients. In total, 12 patients were determined retrospectively to have high-likelihood autoimmune encephalitic diagnoses. The most commonly detected autoantibody specificities were voltage-gated potassium channel ([Kv1] VGKC) complex (6) and calcium channel (P/Q type or N type; 5). Symptoms seen were as follows: depressive (8), anxious (7), psychotic (7), disorganized (5), suicidal (3), manic (1) and catatonic (1). In group 2, among 13 NMDA receptor IgG-positive patients, 12 had encephalitis; their psychiatric symptoms were as follows: depressive (9), catatonic (9), disorganized (8), anxious (8), psychotic (7), manic (6), and suicidal (3). Catatonic symptoms were more common in the 12 NMDA receptor IgG-positive patients than in the 12 group 1 patients with high likelihood of encephalitis (p = 0.002). Antibody positivities were usually low positive in value among healthy controls (12 of 16 vs 3 of 12 group 1 encephalitis cases, p = 0.025). NMDA receptor IgG was not detected in any healthy control subject. A spectrum of psychiatric autoimmunity beyond NMDA-R IgG may be under-recognized. Diagnosis is facilitated by combining results of

Autoimmunity: a decision theory model.

PubMed Central

Morris, J A

1987-01-01

Concepts from statistical decision theory were used to analyse the detection problem faced by the body's immune system in mounting immune responses to bacteria of the normal body flora. Given that these bacteria are potentially harmful, that there can be extensive cross reaction between bacterial antigens and host tissues, and that the decisions are made in uncertainty, there is a finite chance of error in immune response leading to autoimmune disease. A model of ageing in the immune system is proposed that is based on random decay in components of the decision process, leading to a steep age dependent increase in the probability of error. The age incidence of those autoimmune diseases which peak in early and middle life can be explained as the resultant of two processes: an exponentially falling curve of incidence of first contact with common bacteria, and a rapidly rising error function. Epidemiological data on the variation of incidence with social class, sibship order, climate and culture can be used to predict the likely site of carriage and mode of spread of the causative bacteria. Furthermore, those autoimmune diseases precipitated by common viral respiratory tract infections might represent reactions to nasopharyngeal bacterial overgrowth, and this theory can be tested using monoclonal antibodies to search the bacterial isolates for cross reacting antigens. If this model is correct then prevention of autoimmune disease by early exposure to low doses of bacteria might be possible. PMID:3818985

[Autoimmune encephalitis: possibilities in the laboratory investigation].

PubMed

Böröcz, Katalin; Hayden, Zsófia; Mészáros, Viktória; Csizmadia, Zsuzsanna; Farkas, Kornélia; Kellermayer, Zoltán; Balogh, Péter; Nagy, Ferenc; Berki, Tímea

2018-01-01

The role of autoimmune responses against central nervous system (CNS) antigens in encephalitis presenting with non-classified neurologic or psychiatric symptoms has been appreciated in the past decade. Paraneoplastic limbic encephalitis has a poor prognosis and is most commonly associated with lung, ovarium, and testicular neoplasms, leading to immune reactions against intracellular antigens (anti-Hu/ANNA1, anti-Ri/ANNA2, anti-CV2/CRMP5 and anti-Ma2/Ta). In contrast, the recently described autoimmune encephalitis subtypes present with a broad spectrum of symptoms, respond to autoimmune therapies well and usually associate with autoantibodies against neuronal cell surface receptors (NMDAR, GABA B R, AMPAR) or synaptic proteins (LGI1, CASPR2). Our aim is to bring to awareness the increasing number of autoimmune encephalitis patients requiring neurologic, psychiatric and intensive care and to emphasize the significance of detecting various autoantibodies in diagnosing patients. In the past 6 years, our laboratory received 836 autoimmune encephalitis diagnostic test requests from a total of 717 patients. Serum and cerebrospinal fluid (CSF) samples were analysed with indirect immunofluorescence using a BIOCHIP consisting of cell lines transfected with 6 different receptor proteins. IgG autoantibodies against receptor proteins were present in 7.5% of patients. The frequency of positive samples was the following: NMDAR > LGI1 > GABA B R > CASPR2. Detecting autoantibodies facilitates the diagnosis of autoimmune encephalitis in an early stage. Patients diagnosed early can be effectively treated with plasmapheresis and immunosuppressive drugs. The efficiency of therapies can be monitored by autoantibody detection. Therefore, the diagnostic immune laboratory plays an important role in proper diagnosis and in the prevention of rapidly progressing symptoms. Orv Hetil. 2018; 159(3): 107-112.

Minocycline-Induced Drug Hypersensitivity Syndrome Followed by Multiple Autoimmune Sequelae

PubMed Central

Brown, Rebecca J.; Rother, Kristina I.; Artman, Henry; Mercurio, Mary Gail; Wang, Roger; Looney, R. John; Cowen, Edward W.

2010-01-01

Background Drug hypersensitivity syndrome (DHS) is a severe, multisystem adverse drug reaction that may occur following the use of numerous medications, including anticonvulsants, sulfonamides, and minocycline hydrochloride. Long-term autoimmune sequelae of DHS have been reported, including hypothyroidism. Observations A 15-year-old female adolescent developed DHS 4 weeks after starting minocycline therapy for acne vulgaris. Seven weeks later she developed autoimmune hyperthyroidism (Graves disease), and 7 months after discontinuing minocycline therapy she developed autoimmune type 1 diabetes mellitus. In addition, she developed elevated titers of several markers of systemic autoimmune disease, including antinuclear, anti-Sjögren syndrome A, and anti-Smith antibodies. Conclusions Minocycline-associated DHS may be associated with multiple autoimmune sequelae, including thyroid disease, type 1 diabetes mellitus, and elevated markers of systemic autoimmunity. Long-term follow-up is needed in patients with DHS to determine the natural history of DHS-associated sequelae. PMID:19153345

The prevalence of autoimmune disease in patients with esophageal achalasia.

PubMed

Booy, J D; Takata, J; Tomlinson, G; Urbach, D R

2012-04-01

Achalasia is a rare disease of the esophagus that has an unknown etiology. Genetic, infectious, and autoimmune mechanisms have each been proposed. Autoimmune diseases often occur in association with one another, either within a single individual or in a family. There have been separate case reports of patients with both achalasia and one or more autoimmune diseases, but no study has yet determined the prevalence of autoimmune diseases in the achalasia population. This paper aims to compare the prevalence of autoimmune disease in patients with esophageal achalasia to the general population. We retrospectively reviewed the charts of 193 achalasia patients who received treatment at Toronto's University Health Network between January 2000 and May 2010 to identify other autoimmune diseases and a number of control conditions. We determined the general population prevalence of autoimmune diseases from published epidemiological studies. The achalasia sample was, on average, 10-15 years older and had slightly more men than the control populations. Compared to the general population, patients with achalasia were 5.4 times more likely to have type I diabetes mellitus (95% confidence interval [CI] 1.5-19), 8.5 times as likely to have hypothyroidism (95% CI 5.0-14), 37 times as likely to have Sjögren's syndrome (95% CI 1.9-205), 43 times as likely to have systemic lupus erythematosus (95% CI 12-154), and 259 times as likely to have uveitis (95% CI 13-1438). Overall, patients with achalasia were 3.6 times more likely to suffer from any autoimmune condition (95% CI 2.5-5.3). Our findings are consistent with the impression that achalasia's etiology has an autoimmune component. Further research is needed to more conclusively define achalasia as an autoimmune disease. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Epigenomics of autoimmune diseases.

PubMed

Gupta, Bhawna; Hawkins, R David

2015-03-01

Autoimmune diseases are complex disorders of largely unknown etiology. Genetic studies have identified a limited number of causal genes from a marginal number of individuals, and demonstrated a high degree of discordance in monozygotic twins. Studies have begun to reveal epigenetic contributions to these diseases, primarily through the study of DNA methylation, but chromatin and non-coding RNA changes are also emerging. Moving forward an integrative analysis of genomic, transcriptomic and epigenomic data, with the latter two coming from specific cell types, will provide an understanding that has been missed from genetics alone. We provide an overview of the current state of the field and vision for deriving the epigenomics of autoimmunity.

Low Frequencies of Autoimmunity-Associated PTPN22 Polymorphisms in MODY Patients, Including Those Transiently Expressing Islet Cell Autoantibodies.

PubMed

Heneberg, Petr; Malá, Milena; Yorifuji, Tohru; Gat-Yablonski, Galia; Lebenthal, Yael; Tajima, Toshihiro; Nogaroto, Viviane; Rypáčková, Blanka; Kocková, Lucie; Urbanová, Jana; Anděl, Michal

2015-01-01

The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes lymphoid tyrosine phosphatase (LYP), which is expressed primarily in lymphoid tissues. The functional but geographically highly variable PTPN22 single-nucleotide polymorphisms (SNPs), particularly c.1858C>T, contribute to the onset and progression of autoimmunity-associated diseases and facilitate the expression of disease-associated autoantibodies. In Central Europe, 17-25% of patients with monogenic diabetes (maturity-onset diabetes of the young, MODY) transiently express islet cell autoantibodies. We addressed the links between the functional and geographically variable PTPN22 SNPs with MODY manifestation and the expression of islet cell autoantibodies in 276 MODY patients who originated from four regions (the Czech Republic, Israel, Japan and Brazil). The frequency of PTPN22 polymorphisms in the MODY patients was similar to those in geographically matched healthy populations, with the exception of c.788G>A, the minor allele frequency of which was significantly elevated in the Czech hepatocyte nuclear factor 1-α (HNF1A) MODY patients [odds ratio (OR) 4.8, 95% confidence interval (CI) 2.2-10.7] and the Brazilian MODY patients (OR 8.4, 95% CI 1.8-39.1). A barely significant increase in the c.788G>A minor allele was also detected in the islet cell autoantibody-positive Czech MODY patients. However, c.788A behaves as a loss-of-function mutant in T cells, and thus protects against autoimmunity. MODY patients (including islet cell autoantibody-positive cases) do not display any increase in autoimmunity-associated PTPN22 alleles. The absence of autoimmunity-associated PTPN22 alleles was also demonstrated in latent autoimmune diabetes in adults, which suggests that the slow kinetics of the onset of autoantibodies is subject to a regulation that is different from that experienced in type 1 diabetes and other autoimmune disorders. © 2015 S. Karger AG, Basel.

Insulin resistance is associated with larger thyroid volume in adults with type 1 diabetes independently from presence of thyroid autoimmunity.

PubMed

Rogowicz-Frontczak, Anita; Pilacinski, Stanislaw; Chwialkowska, Anna Teresa; Naskret, Dariusz; Zozulinska-Ziolkiewicz, Dorota

2018-04-19

To investigate the effect of insulin resistance (IR) on thyroid function, thyroid autoimmunity (AIT) and thyroid volume in type 1 diabetes (T1DM). 100 consecutive patients with T1DM aged 29 (±6) years with diabetes duration 13 (±6) years were included. Exclusion criteria were: history of thyroid disease, current treatment with L-thyroxin or anti-thyroid drugs. Evaluation of thyroid stimulating hormone (TSH), free thyroid hormones and anti-thyroid antibodies was performed. Thyroid volume was measured by ultrasonography. IR was assessed using the estimated glucose disposal rate (eGDR) formula. In the study group 22% of subjects had insulin resistance defined as eGDR lower or equal to 7.5 mg/kg/min. The prevalence of thyroid autoimmunity (positivity for ATPO or ATg or TRAb) in the study group was 37%. There were no significant differences in the concentration of TSH, FT3, FT4, the prevalence of AIT and hypothyroidism between IR and insulin sensitive (IS) group. Mean (±SD) thyroid volume was 15.6 (±6.2) mL in patients with IR and 11.7 (±4.7) mL in IS subjects (p = .002). Thyroid volume correlated inversely with eGDR (r = -0.35, p < .001). In a multivariate linear regression model the association between thyroid volume and eGDR was independent of sex, age, duration of diabetes, daily insulin dose, BMI, cigarette smoking, TSH value and presence of thyroid autoimmunity (beta: -0.29, p = .012). Insulin resisance is associated with larger thyroid volume in patients with type 1 diabetes independently of sex, body mass index, TSH value and presence of autoimmune thyroid disease.

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

Rare phenotypes in the understanding of autoimmunity

PubMed Central

Zeissig, Yvonne; Petersen, Britt-Sabina; Franke, Andre; Blumberg, Richard S; Zeissig, Sebastian

2017-01-01

The study of rare phenotypes has a long history in the description of autoimmune disorders. First Mendelian syndromes of idiopathic tissue destruction were defined more than 100 years ago and were later revealed to result from immune-mediated reactivity against self. In the past two decades, continuous advances in sequencing technology and particularly the advent of next-generation sequencing have allowed to define the genetic basis of an ever-growing number of Mendelian forms of autoimmunity. This has provided unique insight into the molecular pathways that govern immunological homeostasis and that are indispensable for the prevention of self-reactive immune-mediated tissue damage and ‘horror autotoxicus’. Here we will discuss selected examples of past and recent investigations into rare phenotypes of autoimmunity that have delineated pathways critical for central and peripheral control of the adaptive immune system. We will outline the implications of these findings for rare and common forms of autoimmunity and will discuss the benefits and potential pitfalls of the integration of next-generation sequencing into algorithms for clinical diagnostics. Because of the concise nature of this review, we will focus on syndromes caused by defects in the control of adaptive immunity as innate immune-mediated autoinflammatory disorders have been covered in excellent recent reviews on Mendelian and polygenic forms of autoimmunity. PMID:27562064

Autoimmune liver disease 2007.

PubMed

Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B

2008-01-01

Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

[MAIT cells in autoimmunity].

PubMed

Miyake, Sachiko

2012-01-01

Mucosal associated invariant T (MAIT) cells are restricted by a nonpolymorphic MHC-related molecule-1 (MR1), and express an invariant TCRα chain: Vα7.2-Jα33 in humans and Vα19-Jα33 in mice. MAIT cells are selected in the thymus, but, interestingly, MAIT cells require B cells as well as commensal flora for their peripheral expansion. Bourhis et al demonstrated that MAIT cells display antimicrobial capacity. Both human and mouse MAIT cells have been shown to be activated by Escherichia coli-infected antigen presenting cells in an MR1-dependent manner. MAIT cells show a protective role against Mycobacteriu abscessus or E. coli infections in mice. Human MAIT cells are capable of producing IFNγ and IL-17 and are found in Mycobacterium tuberculosis-infected lung tissues. Thus, MAIT cells play an antimicrobial function under these infectious conditions. MAIT cells play a protective role against autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), whereas they play a pathogenic role in murine models of arthritis. In patients with autoimmune diseases, the frequency of MAIT cells in peripheral blood was significantly reduced. The frequency of MAIT cells reflected the disease activity in MS patients, suggesting the involvement of MAIT cells in the regulation of autoimmune diseases.

Histologic morphometry confirms a prophylactic effect for hyperbaric oxygen in the prevention of delayed radiation enteropathy.

PubMed

Feldmeier, J J; Davolt, D A; Court, W S; Onoda, J M; Alecu, R

1998-01-01

In a previous publication (Feldmeier et al., Radiother Oncol 1995; 35:138-144) we reported our success in preventing delayed radiation enteropathy in a murine model by the application of hyperbaric oxygen (HBO2). In this study we introduce a histologic morphometric technique for assessing fibrosis in the submucosa of these same animal specimens and relate this assay to the previous results. The histologic morphometry, like the previous gross morphometry and compliance assays, demonstrates a significant protective effect for HBO2. The present assay is related to the previous assays in a statistically significant fashion. The predictive value for the histologic morphometric assay demonstrates a sensitivity of 75% and a specificity of 62.5%. The applicability of this assay to other organ systems and its potential superiority to the compliance assay are discussed.

Melkersson-Rosenthal syndrome with Hashimoto thyroiditis in a 9-year-old girl: an autoimmune disorder.

PubMed

Lee, Yun-Jin; Cheon, Chong Kun; Yeon, Gyu Min; Kim, Young Mi; Nam, Sang Ook

2014-05-01

Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown cause. The classical triad of MRS is orofacial edema, recurrent facial paralysis, and a fissured tongue. We present a 9-year-old girl with a recurrent peripheral facial paralysis. She experienced the first episode of a peripheral facial paralysis on the same side without orofacial swelling and lingua plicata 1 year ago. She was diagnosed with Hashimoto thyroiditis 9 months earlier, as confirmed by an endocrinologic investigation. While the patient was hospitalized with recurrent facial paralysis, we found that serum levels of free thyroxine (1.3 ng/dL) and thyrotropin (0.4 uIU/mL) were within normal range, but the level of antithyroperoxidase antibodies (772.0 IU/mL) was very increased. She had been taking an oral prednisolone orally for 2 weeks. At the 1-month follow-up, the patient's symptoms had completely disappeared. The possible correlation between MRS and autoimmune disorders has been documented in only one report, which described an adult with autoimmune thyroiditis (Hashimoto thyroiditis) and MRS. We suggest that the co-occurrence of MRS and Hashimoto thyroiditis is not coincidental but linked to autoimmunity. Copyright © 2014 Elsevier Inc. All rights reserved.

Autoimmune pancreatitis associated with renal lesions mimicking metastatic tumours

PubMed Central

Rudmik, Lucas; Trpkov, Kiril; Nash, Carla; Kinnear, Susan; Falck, Vincent; Dushinski, John; Dixon, Elijah

2006-01-01

Autoimmune pancreatitis is a chronic inflammatory disorder that is often misdiagnosed as pancreatic cancer. Since autoimmune pancreatitis is benign and responds to steroid management, it is important to diagnose it to avoid unnecessary surgical intervention. We describe a novel case of IgG4-associated autoimmune pancreatitis presenting with tubulointerstitial nephritis as renal lesions mimicking metastatic tumours but with no change in renal function. PMID:16908897

Thromboembolism in Dogs with Protein-Losing Enteropathy with Non-Neoplastic Chronic Small Intestinal Disease.

PubMed

Jacinto, Ana M L; Ridyard, Alison E; Aroch, Itamar; Watson, Penny J; Morrison, Linda R; Chandler, Marge L; Kuzi, Sharon

Dogs with protein-losing enteropathy (PLE) are suggested to be at increased risk of developing thromboembolic events. However, with some exceptions, there are very few reports of thromboembolism in such dogs. This multicentre retrospective observational study describes a case series of thromboembolism (TE) in eight dogs with PLE secondary to non-neoplastic, chronic small intestinal disease. Seven dogs had poorly controlled PLE when the thromboembolic event occurred. Pulmonary thromboembolism (PTE) occurred in six dogs, while one dog developed splenic vein thrombosis and another had concurrent splenic vein and aortic TE. Six dogs died, all with PTE. Antithrombin activity was decreased in one of two dogs in which it was measured. Serum cobalamin and folate concentrations were measured in three dogs and cobalamin was subnormal in all three. Serum magnesium, measured in two dogs, was low in both. Dogs with uncontrolled chronic small intestinal disease and PLE are at risk for developing serious life-threatening TE, mostly PTE.

[Diarrhea with malabsorption and exudative enteropathy caused by intestinal myeloid involvement in a patient with myeloproliferative syndrome].

PubMed

Molas, G; Ponsot, P; Solal-Celigny, P; Amar, M; Paolaggi, J A; Potet, F; Henin, D

1992-01-01

A 41-year-old woman with a myelodysplastic syndrome complained of diarrhea with malabsorption and protein-losing enteropathy after splenectomy. No cause was found and various therapeutic regimens were not effective. Pathological examination of biopsies from stomach, small intestine, and large bowel showed infiltrations interpreted as inflammatory on routine technics. Blast cell infiltration was found on electron microscopy. Treatment by citarabine induced normalization of leukocytosis, and diarrhea disappeared. Six months after the onset of illness, she developed acute myeloblastic leukemia and died of infectious pneumonia. Blastic infiltration of the lamina propria could be responsible for the determinism of symptoms, because of the lack of another etiology, the intensity of the blastic infiltration and the effect of cytotoxic therapy, even in the absence of new biopsies.

Thyroid autoimmunity in bipolar disorder: A systematic review.

PubMed

Barbuti, Margherita; Carvalho, André F; Köhler, Cristiano A; Murru, Andrea; Verdolini, Norma; Guiso, Giovanni; Samalin, Ludovic; Maes, Michael; Stubbs, Brendon; Perugi, Giulio; Vieta, Eduard; Pacchiarotti, Isabella

2017-10-15

Accumulating evidence points to the pathophysiological relevance between immune dysfunction and mood disorders. High rates of thyroid dysfunction have been found in patients with bipolar disorder (BD), compared to the general population. A systematic review of the relationship between BD and thyroid autoimmunity was performed. Pubmed, EMBASE and PsycINFO databases were searched up till January 28th, 2017. This review has been conducted according to the PRISMA statements. Observational studies clearly reporting data among BD patients and the frequency of autoimmune thyroid pathologies were included. 11 original studies met inclusion criteria out of 340 titles first returned from the global search. There is evidence of increased prevalence of circulating thyroid autoantibodies in depressed and mixed BD patients, while there is no evidence showing a positive relationship between BD and specific autoimmune thyroid diseases. There is a controversy about the influence of lithium exposure on circulating thyroid autoantibodies, even if most of studies seem not to support this association. A study conducted on bipolar twins suggests that autoimmune thyroiditis is related to the genetic vulnerability to develop BD rather than to the disease process itself. Females are more likely to develop thyroid autoimmunity. The samples, study design and outcomes were heterogeneous. Thyroid autoimmunity has been suggested to be an independent risk factor for bipolar disorder with no clear association with lithium exposure and it might serve as an endophenotype for BD. Copyright © 2017 Elsevier B.V. All rights reserved.

Research Techniques Made Simple: Mouse Models of Autoimmune Blistering Diseases.

PubMed

Pollmann, Robert; Eming, Rüdiger

2017-01-01

Autoimmune blistering diseases are examples of autoantibody-mediated, organ-specific autoimmune disorders. Based on a genetic susceptibility, such as a strong HLA-class II association, as yet unknown triggering factors induce the formation of circulating and tissue-bound autoantibodies that are mainly directed against adhesion structures of the skin and mucous membranes. Compared with other autoimmune diseases, especially systemic disorders, the pathogenicity of autoimmune blistering diseases is relatively well described. Several animal models of autoimmune blistering diseases have been established that helped to uncover the immunological and molecular mechanisms underlying the blistering phenotypes. Each in vivo model focuses on specific aspects of the autoimmune cascade, from loss of immunological tolerance on the level of T and B cells to the pathogenic effects of autoantibodies upon binding to their target autoantigen. We discuss current mouse models of autoimmune blistering diseases, including models of pemphigus vulgaris, bullous pemphigoid, epidermolysis bullosa acquisita, and dermatitis herpetiformis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Explosion of autoimmune diseases and the mosaic of old and novel factors

PubMed Central

Agmon-Levin, Nancy; Lian, Zhexiong; Shoenfeld, Yehuda

2011-01-01

In recent decades, an enormous effort has been made to elucidate the pathogenesis of autoimmune and autoinflammatory diseases. Autoimmunity is a multifactorial process in which genetic, immunological, environmental and hormonal factors play in concert, together representing what was termed years ago the ‘mosaic of autoimmunity'. To date, more than 80 systemic and organ-specific autoimmune diseases have been defined, and their cumulative burden is substantial, both medically and financially. Furthermore, the burden of autoimmune and autoinflammatory diseases is rising, making these diseases a ubiquitous global phenomenon that is predicted to further increase in the coming decades. In this issue of the journal, additional aspects of autoimmunity are detailed. Immune dysregulation and loss of self-tolerance are the cornerstones of autoimmunity. PMID:21358666

Family occurrence of autoimmune hepatitis: A Danish nationwide registry-based cohort study.

PubMed

Grønbæk, Lisbet; Vilstrup, Hendrik; Pedersen, Lars; Christensen, Kaare; Jepsen, Peter

2018-06-06

It is widely believed that autoimmune hepatitis accumulates in families, but the degree of familial clustering has not been clarified. We conducted a population-based study on the family occurrence of autoimmune hepatitis. Through Danish nationwide registries we identified 8,582 first-degree and 9,230 second-degree relatives of index patients diagnosed with autoimmune hepatitis in 1994-2015; and 64 co-twins of index patients diagnosed with autoimmune hepatitis in 1977-2011. For first- and second-degree relatives we calculated the sex- and age-adjusted standardized incidence ratio of autoimmune hepatitis relative to the general population, and we calculated the cumulative risk, i.e. the cumulative incidence, of developing autoimmune hepatitis from the time of the index patient's diagnosis. For co-twins, we estimated the standardized incidence ratio and the concordance rate of autoimmune hepatitis. In first-degree relatives, there were six incident autoimmune hepatitis diagnoses during 64,020 years of follow-up: the standardized incidence ratio was 4.9 (95% CI 1.8-10.7), and the 10-year cumulative risk was 0.10% (95% CI 0.04-0.23). In the second-degree relatives, there were no incident autoimmune hepatitis diagnoses (expected number assuming incidence rate as in the Danish general population = 0.8). In the co-twins, there was one incident autoimmune hepatitis diagnosis during 1,112 years of follow-up, and the standardized incidence ratio was 53.9 (95% CI 1.4-300.4). The probandwise concordance rate, a measure of heritability, was higher in monozygotic than in dizygotic twins (8.7% [95% CI 1.1-28.0] vs. 0%). This nationwide study indicates that only first-degree relatives of index patients with autoimmune hepatitis are at increased risk of autoimmune hepatitis from the time of the index patient's diagnosis, but the absolute risk is very low. Autoimmune hepatitis is a chronic liver disease caused by a dysfunctional immune system. It is widely believed that autoimmune

Scurfy mice: A model for autoimmune disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 somore » 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.« less

Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland.

PubMed

Jackson, Yves; Pula, Drenusha Vieira de Mello; Finckh, Axel; Chizzolini, Carlo; Chappuis, François

2018-02-05

Chronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease. We tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy. We retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases. Of the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI) = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3%) patient, of whom 244 (27.0%; 95% CI = 24.2-30.0%) were positive. Eight (28.6%; 95% CI = 15.3-47.1%) of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000) or with Chagasic cardiomyopathy (p = 0.729). Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases. Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection.

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

Ionizing radiation and autoimmunity: Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakaguchi, N.; Sakaguchi, S.; Miyai, K.

1992-11-01

Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and themore » peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4[sup +] T cells mediated the autoimmune prevention but CD8[sup +] T cells did not. CD4[sup +] T cells also appeared to mediate the TLI-induced autoimmune disease because CD4[sup +] T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs.« less

Antiviral immune responses: triggers of or triggered by autoimmunity?

PubMed Central

Münz, Christian; Lünemann, Jan D.; Getts, Meghann Teague; Miller, Stephen D.

2010-01-01

Several common autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and multiple sclerosis, are genetically linked to distinct human MHC class II molecules and other immune modulators. However, genetic predisposition is only one risk factor for the development of these diseases, and low concordance rates in monozygotic twins as well as geographical distribution of disease risk point towards environmental factors in the genesis of these diseases. Among these environmental factors, infections have been implicated in the onset and/or promotion of autoimmunity. In this review, we outline mechanisms by which pathogens can trigger autoimmune disease, and also pathways by which infection and immune control of infectious disease might be dysregulated during autoimmunity. PMID:19319143

Epstein-Barr Virus as a Trigger of Autoimmune Liver Diseases

PubMed Central

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

2012-01-01

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

Parallel Aspects of the Microenvironment in Cancer and Autoimmune Disease

PubMed Central

Rahat, Michal A.

2016-01-01

Cancer and autoimmune diseases are fundamentally different pathological conditions. In cancer, the immune response is suppressed and unable to eradicate the transformed self-cells, while in autoimmune diseases it is hyperactivated against a self-antigen, leading to tissue injury. Yet, mechanistically, similarities in the triggering of the immune responses can be observed. In this review, we highlight some parallel aspects of the microenvironment in cancer and autoimmune diseases, especially hypoxia, and the role of macrophages, neutrophils, and their interaction. Macrophages, owing to their plastic mode of activation, can generate a pro- or antitumoral microenvironment. Similarly, in autoimmune diseases, macrophages tip the Th1/Th2 balance via various effector cytokines. The contribution of neutrophils, an additional plastic innate immune cell population, to the microenvironment and disease progression is recently gaining more prominence in both cancer and autoimmune diseases, as they can secrete cytokines, chemokines, and reactive oxygen species (ROS), as well as acquire an enhanced ability to produce neutrophil extracellular traps (NETs) that are now considered important initiators of autoimmune diseases. Understanding the contribution of macrophages and neutrophils to the cancerous or autoimmune microenvironment, as well as the role their interaction and cooperation play, may help identify new targets and improve therapeutic strategies. PMID:26997761

Autoimmune disease: A role for new anti-viral therapies?

PubMed

Dreyfus, David H

2011-12-01

Many chronic human diseases may have an underlying autoimmune mechanism. In this review, the author presents a case of autoimmune CIU (chronic idiopathic urticaria) in stable remission after therapy with a retroviral integrase inhibitor, raltegravir (Isentress). Previous reports located using the search terms "autoimmunity" and "anti-viral" and related topics in the pubmed data-base are reviewed suggesting that novel anti-viral agents such as retroviral integrase inhibitors, gene silencing therapies and eventually vaccines may provide new options for anti-viral therapy of autoimmune diseases. Cited epidemiologic and experimental evidence suggests that increased replication of epigenomic viral pathogens such as Epstein-Barr Virus (EBV) in chronic human autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), and multiple sclerosis (MS) may activate endogenous human retroviruses (HERV) as a pathologic mechanism. Memory B cells are the reservoir of infection of EBV and also express endogenous retroviruses, thus depletion of memory b-lymphocytes by monoclonal antibodies (Rituximab) may have therapeutic anti-viral effects in addition to effects on B-lymphocyte presentation of both EBV and HERV superantigens. Other novel anti-viral therapies of chronic autoimmune diseases, such as retroviral integrase inhibitors, could be effective, although not without risk. Copyright © 2011 Elsevier B.V. All rights reserved.

Autoimmunity in narcolepsy.

PubMed

Bonvalet, Melodie; Ollila, Hanna M; Ambati, Aditya; Mignot, Emmanuel

2017-11-01

Summarize the recent findings in narcolepsy focusing on the environmental and genetic risk factors in disease development. Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Recent studies suggest both humoral and cellular immune responses in the disease development. Narcolepsy is a severe sleep disorder, in which neurons producing orexin/hypocretin in the hypothalamus are destroyed. The core symptoms of narcolepsy are debilitating, extreme sleepiness, cataplexy, and abnormalities in the structure of sleep. Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Importantly, the highest environmental risk is seen with influenza-A infection and immunization. However, how the cells are destroyed is currently unknown. In this review we summarize the disease symptoms, and focus on the immunological findings in narcolepsy. We also discuss the environmental and genetic risk factors as well as propose a model for disease development.

Chronic autoimmune disorders are increased in coeliac disease: A case-control study.

PubMed

Bibbò, Stefano; Pes, Giovanni Mario; Usai-Satta, Paolo; Salis, Roberta; Soro, Sara; Quarta Colosso, Bianca Maria; Dore, Maria Pina

2017-11-01

Coeliac disease (CD) is an autoimmune disorder of the small bowel associated with increased risk of additional autoimmune diseases (ADs).To investigate the prevalence of ADs in a population of adult coeliac patients.This was a retrospective case-control study. Data from coeliac patients and controls referred to a tertiary center between 2013 and 2016 were collected. The frequency of ADs and the unadjusted and adjusted odds ratios (ORs) for age, gender, disease duration, and body mass index with their 95% confidence intervals (CIs) were evaluated.Two hundred fifty-five patients with CD (median age 37.1 years; 206 women) were matched with 250 controls. ADs were more frequent (35.3%) in coeliac patients than in controls (15.2%). Adjusted ORs for the presence of only 1, at least 1, and more than 1 AD were 3.13 (95% CI 1.81-5.42, P < .0001), 3.31 (95% CI 2.00-5.46, P < .0001), and 3.93 (95% CI 1.49-10.36, P = .006), respectively. Hashimoto thyroiditis was the most prevalent AD (24.3% vs. 10%) OR = 2.55 (95% CI 1.39-4.70, P < .0001), followed by psoriasis (4.3% vs. 1.6%), type 1 diabetes (2.7% vs. 0.4%), and Sjögren syndrome (2.4% vs. 0.4%).These findings suggest a need for a careful surveillance of autoimmune status, especially for Hashimoto thyroiditis in patients with celiac disease. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

B cell modulation strategies in autoimmunity: the SLE example.

PubMed

Rosado, M Manuela; Diamanti, Andrea Picchianti; Capolunghi, Federica; Carsetti, Rita

2011-01-01

The paradigm that T cells are the prime effectors of autoimmune diseases has been recently challenged by growing evidence that B-lymphocytes play a role in the development, re-activation and persistence of autoimmune disorders. B-cells of different subsets may play different roles in autoimmune pathologies due to their ability to secrete antibodies, produce cytokines, present antigen and form ectopic germinal centers. Thus, a given therapeutic approach or drug may have distinct outcomes depending on which specific B cell subset is targeted. Immunosuppressive therapies such as azathioprine (AZA), cyclophosphamide (CyC) or methotrexate (MTX) are conventionally used in autoimmune diseases with the aim of reducing disease activity and improving the patient's general health conditions. These treatments do not target a specific cellular type or subset and have substantial side effects, such as impairment of liver function and fertility. Moreover, autoimmune patients may be refractory to immunosuppressive therapy. In these cases finding an effective treatment becomes a challenge. The fast evolution in antibody technology is leading to the production of a wide array of humanized monoclonal antibodies, targeting specific cell types or pathways, initiating a new era in the treatment of autoimmune disorders. In addition, the recent discovery that toll like receptors (TLRs) activation can fire up autoimmunity in humans and maintain disease gives the grounds for the development of new drugs targeting the TLR/MyD88 pathway. In contrast to conventional immune-suppression, the availability of drugs interfering with B-cell specific pathogenetic pathways gives the possibility to choose therapies tailored to each disease and, possibly, to each patient.

Celiac disease and other autoimmune diseases in patients with collagenous colitis.

PubMed

Vigren, Lina; Tysk, Curt; Ström, Magnus; Kilander, Anders F; Hjortswang, Henrik; Bohr, Johan; Benoni, Cecilia; Larson, Lasse; Sjöberg, Klas

2013-08-01

Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland

PubMed Central

Jackson, Yves; Pula, Drenusha Vieira de Mello; Finckh, Axel; Chizzolini, Carlo; Chappuis, François

2018-01-01

BACKGROUND Chronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease. OBJECTIVES We tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy. METHODS We retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases. FINDINGS Of the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI) = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3%) patient, of whom 244 (27.0%; 95% CI = 24.2-30.0%) were positive. Eight (28.6%; 95% CI = 15.3-47.1%) of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000) or with Chagasic cardiomyopathy (p = 0.729). Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases. CONCLUSIONS Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection. PMID:29412344

The impact of abnormal autoimmune function on reproduction: maternal and fetal consequences.

PubMed

Gleicher, Norbert; Weiner, Rebecca; Vietzke, Mary

2006-11-01

The impact of abnormal autoimmune function on reproductive success has remained a highly controversial issue. This is, at least partially, due to the relative lack of demographic data from women with established autoimmune diseases. We, therefore, investigated 163 women with proven autoimmune diseases and 73 controls in a demographic study of reproductive success and impact of abnormal autoimmunity on pregnancy and offspring. Women with autoimmune diseases experienced fewer pregnancies overall (p=0.04) and fewer pregnancy losses (p=0.05). Offspring from women with autoimmune diseases demonstrated a significantly increased prevalence of confirmed autoimmune diseases (p=0.04; OR 3.759; 95%CL 1.04-1.27), which increased further if suspected, but not yet confirmed, cases were added (p=0.001; OR 8.592; 95%CL 1.05-55.0). Women with autoimmune diseases exhibited a trend towards lower cesarean section delivery during their own birth and a significantly increased prevalence of disease in vaginally delivered offspring (p=0.014; OR 6.041; 95%CL 1.32-38.22). Autoimmune diseases impair female fecundity even before the diseases become clinically overt. Offspring are at increased risk to develop autoimmune diseases, though they may differ from those of their mothers. This risk appears to correlate with mode of delivery and may be the consequence of varying cell traffic dynamics with vaginal and cesarean section deliveries.

Complement in autoimmune diseases.

PubMed

Vignesh, Pandiarajan; Rawat, Amit; Sharma, Madhubala; Singh, Surjit

2017-02-01

The complement system is an ancient and evolutionary conserved element of the innate immune mechanism. It comprises of more than 20 serum proteins most of which are synthesized in the liver. These proteins are synthesized as inactive precursor proteins which are activated by appropriate stimuli. The activated forms of these proteins act as proteases and cleave other components successively in amplification pathways leading to exponential generation of final effectors. Three major pathways of complement pathways have been described, namely the classical, alternative and lectin pathways which are activated by different stimuli. However, all the 3 pathways converge on Complement C3. Cleavage of C3 and C5 successively leads to the production of the membrane attack complex which is final common effector. Excessive and uncontrolled activation of the complement has been implicated in the host of autoimmune diseases. But the complement has also been bemusedly described as the proverbial "double edged sword". On one hand, complement is the final effector of tissue injury in autoimmune diseases and on the other, deficiencies of some components of the complement can result in autoimmune diseases. Currently available tools such as enzyme based immunoassays for functional assessment of complement pathways, flow cytometry, next generation sequencing and proteomics-based approaches provide an exciting opportunity to study this ancient yet mysterious element of innate immunity. Copyright © 2017 Elsevier B.V. All rights reserved.

Immunopathogenesis and Therapeutic Approaches in Pediatric Celiac Disease

PubMed Central

Agarwal, Shreya; Kovilam, Oormila; Zach, Terence L.; Agrawal, Devendra K.

2016-01-01

Summary Celiac Disease is an autoimmune enteropathy with increasing incidence worldwide in both adults and children. It occurs as an inflammatory condition with destruction of the normal architecture of villi on consumption of gluten and related protein products found in wheat, barley and rye. However, the exact pathogenesis is not yet fully understood. A gluten-free diet remains the main modality of therapy to date. While some patients continue to have symptoms even on a gluten-free diet, adherence to this diet is also difficult, especially for the children. Hence, there is continued interest in novel methods of therapy and the current research focus is on the promising novel non-dietary modalities of treatment. Here, we critically reviewed the existing literature regarding the pathogenesis of celiac disease in children including the role of in-utero exposure leading to neonatal and infant sensitization and its application for the development of new therapeutic approaches for these patients. PMID:26999328

Emerging drugs for coeliac disease.

PubMed

Mooney, Peter D; Hadjivassiliou, Marios; Sanders, David S

2014-12-01

Coeliac disease is an autoimmune gluten sensitive enteropathy and is now known to affect 1% of the adult population. A gluten-free diet (GFD) should be curative; however, up to 30% of patients have persistent symptoms and many patients find the diet difficult to fully adhere to. Currently, there are no licensed therapeutic options for patients with coeliac disease outside of a GFD. This review will outline the case for alternative treatments and discuss the potential therapeutic targets. The products in the most advanced stage of development will be discussed in detail. There is clearly an unmet need for alternatives to a GFD for the treatment of coeliac disease. Oral glutenase supplements to improve the degradation of gluten into non-toxic peptides appear to be the most likely to provide a breakthrough in the treatment of coeliac disease; however, other modalities such as a therapeutic vaccine or zonulin inhibitors to reduce intestinal permeability have shown promising results.

Obesity, islet cell autoimmunity, and cardiovascular risk factors in youth at onset of type 1 autoimmune diabetes.

PubMed

Cedillo, Maribel; Libman, Ingrid M; Arena, Vincent C; Zhou, Lei; Trucco, Massimo; Ize-Ludlow, Diego; Pietropaolo, Massimo; Becker, Dorothy J

2015-01-01

The current increase in childhood type 1 diabetes (T1D) and obesity has led to two conflicting hypotheses and conflicting reports regarding the effects of overweight on initiation and spreading of islet cell autoimmunity vs earlier clinical manifestation of preexisting autoimmune β-cell damage driven by excess weight. The objective of the study was to address the question of whether the degree of β-cell autoimmunity and age are related to overweight at diabetes onset in a large cohort of T1D youth. This was a prospective cross-sectional study of youth with autoimmune T1D consecutively recruited at diabetes onset. The study was conducted at a regional academic pediatric diabetes center. Two hundred sixty-three consecutive children younger than 19 years at onset of T1D participated in the study. Relationships between body mass index and central obesity (waist circumference and waist to height ratio) and antigen spreading (islet cell autoantibody number), age, and cardiovascular (CVD) risk factors examined at onset and/or 3 months after the diagnosis were measured. There were no significant associations between number of autoantibodies with measures of adiposity. Age relationships revealed that a greater proportion of those with central obesity (21%) were in the youngest age group (0-4 y) compared with those without central obesity (6%) (P = .001). PATIENTS with central obesity had increased CVD risk factors and higher onset C-peptide levels (P < .05). No evidence was found to support the concept that obesity accelerates progression of autoantibody spreading once autoimmunity, marked by standard islet cell autoantibody assays, is present. Central obesity was present in almost one-third of the subjects and was associated with early CVD risk markers already at onset.

Emerging role of IL-35 in inflammatory autoimmune diseases.

PubMed

Su, Lin-Chong; Liu, Xiao-Yan; Huang, An-Fang; Xu, Wang-Dong

2018-05-03

Interleukin 35 (IL-35) is the recently identified member of the IL-12 family of cytokines and provides the possibility to be a target for new therapies for autoimmune, inflammatory diseases. It is composed of an α chain (p35) and a β chain (EBI3). IL-35 mediates signaling by binding to its receptors, activates subsequent signaling pathways, and therefore, regulates the differentiation, function of T, B cells, macrophages, dendritic cells. Recent findings have shown abnormal expression of IL-35 in inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, psoriasis, multiple sclerosis, autoimmune hepatitis, experimental autoimmune uveitis. In addition, functional analysis suggested that IL-35 is critical in the onset and development of these diseases. Therefore, the present study will systematically review what had been occurred regarding IL-35 in inflammatory autoimmune disease. The information collected will help to understand the biologic role of IL-35 in immune cells, and give information about the therapeutic potential of IL-35 in these diseases. Copyright © 2018. Published by Elsevier B.V.

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. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Autoimmune Addison disease: pathophysiology and genetic complexity.

PubMed

Mitchell, Anna L; Pearce, Simon H S

2012-01-31

Autoimmune Addison disease is a rare autoimmune disorder with symptoms that typically develop over months or years. Following the development of serum autoantibodies to the key steroidogenic enzyme, 21-hydroxylase, patients have a period of compensated or preclinical disease, characterized by elevations in adrenocortocotropic hormone and renin, before overt, symptomatic adrenal failure develops. We propose that local failure of steroidogenesis, causing breakdown of tolerance to adrenal antigens, might be a key factor in disease progression. The etiology of autoimmune Addison disease has a strong genetic component in man, and several dog breeds are also susceptible. Allelic variants of genes encoding molecules of both the adaptive and innate immune systems have now been implicated, with a focus on the immunological synapse and downstream participants in T lymphocyte antigen-receptor signaling. With the exception of MHC alleles, which contribute to susceptibility in both human and canine Addison disease, no major or highly penetrant disease alleles have been found to date. Future research into autoimmune Addison disease, making use of genome-wide association studies and next-generation sequencing technology, will address the gaps in our understanding of the etiology of this disease.

Autoimmunity and the risk of myeloproliferative neoplasms

PubMed Central

Kristinsson, Sigurdur Y.; Landgren, Ola; Samuelsson, Jan; Björkholm, Magnus; Goldin, Lynn R.

2010-01-01

The causes of myeloproliferative neoplasm (MPN) are unknown. We conducted a large population-based study including 11,039 myeloproliferative neoplasm patients and 43,550 matched controls with the aim of assessing the associations between a personal history of a broad span of autoimmune diseases and subsequent risk of myeloproliferative neoplasm. We found a prior history of any autoimmune disease to be associated with a significantly increased risk of myeloproliferative neoplasms (odds ratio (OR)=1.2; 95% confidence interval (CI) 1.0–1.3; P=0.021). Specifically, we found an increased risk of MPNs associated with a prior immune thrombocytopenic purpura (2.9; 1.7–7.2), Crohn’s disease (1.8; 1.1–3.0), polymyalgia rheumatica (1.7; 1.2–2.5), giant cell arteritis (5.9; 2.4–14.4), Reiter’s syndrome (15.9; 1.8–142) and aplastic anemia (7.8; 3.7–16.7). The risk of myeloproliferative neoplasms associated with prior autoimmune diseases is modest but statistically significant. Future studies are needed to unravel the effects of these autoimmune diseases themselves, their treatment, or common genetic susceptibility. PMID:20053870

Evaluation of autoimmune thyroid disease in melasma.

PubMed

Rostami Mogaddam, Majid; Iranparvar Alamdari, Manouchehr; Maleki, Nasrollah; Safavi Ardabili, Nastaran; Abedkouhi, Selma

2015-06-01

Melasma is one of the most frequently acquired hyperpigmentation disorders clinically characterized by symmetrical brown patches on sun-exposed areas. To date, few studies have been conducted about the relationship between thyroid autoimmun-ity and melasma. To evaluate the thyroid dysfunction and autoimmunity in nonpregnant women with melasma. A total of 70 women with melasma and 70 age-matched healthy women with no history of melasma were enrolled in the study. We studied the thyroid hormone profile in both groups. The statistical analysis was performed using SPSS software. Patients with melasma had 18.5% frequency of thyroid disorders, and 15.7% had positive anti-TPO, while subjects from the control group had a 4.3% frequency of thyroid abnormalities, and only 5.7% had positive anti-TPO. There was a significantly higher prevalence of thyroid dysfunction in women with melasma compared with control group (P = 0.008). This study suggests that there is a relationship between thyroid autoimmunity and melasma. However, to make recommendations on screening for thyroid disease in patients with melasma, future research of good methodological quality is needed. © 2015 Wiley Periodicals, Inc.

A clinical approach to diagnosis of autoimmune encephalitis

PubMed Central

Graus, Francesc; Titulaer, Maarten J; Balu, Ramani; Benseler, Susanne; Bien, Christian G; Cellucci, Tania; Cortese, Irene; Dale, Russell C; Gelfand, Jeffrey M; Geschwind, Michael; Glaser, Carol A; Honnorat, Jerome; Höftberger, Romana; Iizuka, Takahiro; Irani, Sarosh R; Lancaster, Eric; Leypoldt, Frank; Prüss, Harald; Rae-Grant, Alexander; Reindl, Markus; Rosenfeld, Myrna R; Rostásy, Kevin; Saiz, Albert; Venkatesan, Arun; Vincent, Angela; Wandinger, Klaus-Peter; Waters, Patrick; Dalmau, Josep

2016-01-01

Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis. Because autoantibody test results and response to therapy are not available at disease onset, we based the initial diagnostic approach on neurological assessment and conventional tests that are accessible to most clinicians. Through logical differential diagnosis, levels of evidence for autoimmune encephalitis (possible, probable, or definite) are achieved, which can lead to prompt immunotherapy. PMID:26906964

Drug delivery technologies for autoimmune disease.

PubMed

Phillips, Brett E; Giannoukakis, Nick

2010-11-01

Targeting autoimmune disease poses two main challenges. The first is to identify unique targets to suppress directly or indirectly autoreactive cells exclusively. The second is to penetrate target tissues to deliver specifically drugs to desired cells that can achieve a therapeutic outcome. Herein, the range of drug delivery methods available and under development and how they can be useful to treat autoimmune diseases are discussed. Polymer delivery methods, as well as biological methods that include fusion proteins, targeted antibodies, recombinant viruses and cell products are compared. Readers will gain insight into the progression of clinical trials for different technologies and drug delivery methods useful for targeting and modulating the function of autoreactive immune cells. Several tissue-specific polymer-based and biologic drug delivery systems are now in Phase II/III clinical trials. Although these trials are focused mainly on cancer treatment, lessons from these trials can guide the use of the same agents for autoimmunity therapeutics.

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

Avian models with spontaneous autoimmune diseases

PubMed Central

Wick, Georg; Andersson, Leif; Hala, Karel; Gershwin, M. Eric; Selmi, Carlo F.; Erf, Gisela F.; Lamont, Susan J.; Sgonc, Roswitha

2012-01-01

Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible any more. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models - albeit rare – reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present review describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and 206) with a scleroderma-like disease and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome. PMID:17145302

Heritability versus the role of the environment in autoimmunity.

PubMed

Selmi, Carlo; Lu, Qianjin; Humble, Michael C

2012-12-01

The higher concordant occurrence of autoimmune diseases in monozygotic twins compared to dizygotic or sibling pairs supports the role for genetic susceptibility. For most conditions, however, concordance rates are considerably below 100% and lead to the estimate of the weight of genetics coined "heritability". In the group of autoimmune diseases heritability ranges between 0.008 and 1 with median values of approximately 0.60. A complementary term coined "environmentability" represents the environmental influence on individual phenotype, and can include dietary habits, chemicals, or hygienic conditions. Genome-wide association data in complex diseases confirmed a role for the environment in disease etiology as significantly associated polymorphisms were found only in subgroups of patients and controls. Environmental links to autoimmunity range from anecdotal associations or case series to largely investigated experimental and epidemiological studies. A bibliographic analysis reveals that the number of publications dedicated to environmental factors in autoimmunity has grown on average by 7% every year since 1997. The National Institute of Environmental Health Sciences (NIEHS) convened an expert panel workshop to review the body of literature examining the role of the environment in the development of autoimmune disease and to identify conclusions, confidences, and critical knowledge gaps in this area. The results of the workshop discussion are summarized in the articles found in this issue of the Journal of Autoimmunity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases.

PubMed

Utiyama, Shirley R R; Zenatti, Katiane B; Nóbrega, Heloisa A J; Soares, Juliana Z C; Skare, Thelma L; Matsubara, Caroline; Muzzilo, Dominique A; Nisihara, Renato M

2016-08-01

Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.

Nitrosative Stress and Nitrated Proteins in Trichloroethene-Mediated Autoimmunity

PubMed Central

Wang, Gangduo; Wang, Jianling; Luo, Xuemei; Ansari, G. A. Shakeel; Khan, M. Firoze

2014-01-01

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, has been linked to a variety of autoimmune diseases (ADs) including SLE, scleroderma and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely unknown. Earlier studies from our laboratory in MRL+/+ mice suggested the contribution of oxidative/nitrosative stress in TCE-induced autoimmunity, and N-acetylcysteine (NAC) supplementation provided protection by attenuating oxidative stress. This study was undertaken to further evaluate the contribution of nitrosative stress in TCE-mediated autoimmunity and to identify proteins susceptible to nitrosative stress. Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, ∼250 mg/kg/day via drinking water). TCE exposure led to significant increases in serum anti-nuclear and anti-histone antibodies together with significant induction of iNOS and increased formation of nitrotyrosine (NT) in sera and livers. Proteomic analysis identified 14 additional nitrated proteins in the livers of TCE-treated mice. Furthermore, TCE exposure led to decreased GSH levels and increased activation of NF-κB. Remarkably, NAC supplementation not only ameliorated TCE-induced nitrosative stress as evident from decreased iNOS, NT, nitrated proteins, NF-κB p65 activation and increased GSH levels, but also the markers of autoimmunity, as evident from decreased levels of autoantibodies in the sera. These findings provide support to the role of nitrosative stress in TCE-mediated autoimmune response and identify specific nitrated proteins which could have autoimmune potential. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for designing therapeutic strategies. PMID:24892995

Conference scene: shining lights on the future of autoimmunity in Asia.

PubMed

Perricone, Carlo; Perricone, Roberto

2012-03-01

The Congress on Autoimmunity was held, as was the previous 4th Asian Congress on Autoimmunity meeting, in Suntec City, Singapore, on 17-19 November 2011. The congress saw the participation of prestigious experts within the fields of autoimmunity, immunology, rheumatology, cardiovascular diseases and diabetology, with the enlightening concepts discussed briefly summarized herein. The Honorary President of the congress, Yehuda Shoenfeld, together with the local and international organizing committees, successfully put together an attractive scientific program with topics including the most up-to-date achievements and discoveries in all aspects of autoimmunity. In the surrounding of a beautiful city, autoimmunity was untangled, and novel, brilliant ideas emerged that could help to solve this fascinating conundrum.

Viruses as triggers of autoimmunity: facts and fantasies.

PubMed

Whitton, J L; Fujinami, R S

1999-08-01

Autoimmunity has been proposed as the cause of several human chronic inflammatory diseases, and recent animal studies show that viruses can induce autoimmune disease. These studies demonstrate how viruses might misdirect the immune system, and here we discuss critically the evidence that similar phenomena may lead to human disease.

Successful Treatment of Protein-Losing Enteropathy Induced by Intestinal Lymphangiectasia in a Liver Cirrhosis Patient with Octreotide: A Case Report

PubMed Central

Lee, Hang Lak; Kim, Jin Bae; Jeon, Yong Chul; Sohn, Joo Hyun; Hahm, Joon Soo

2004-01-01

A 47-yr-old man with hepatitis B virus associated liver cirrhosis was admitted to our hospital with diarrhea and generalized edema and diagnosed as protein-losing enteropathy due to intestinal lymphangiectasia by intestinal biopsy and 99mTc albumin scan. During hospitalization, he received subcutaneous octreotide therapy. After 2 weeks of octreotide therapy, follow-up albumin scan showed no albumin leakage, and the serum albumin level was sustained. We speculate that liver cirrhosis can be a cause of intestinal lymphangiectasia and administration of octreotide should be considered for patients with intestinal lymphangiectasia whose clinical and biochemical abnormalities do not respond to a low-fat diet. PMID:15201518

Antimicrobial Susceptibility Testing of Two Lawsonia intracellularis Isolates Associated with Proliferative Hemorrhagic Enteropathy and Porcine Intestinal Adenomatosis in South Korea▿

PubMed Central

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

2011-01-01

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

Estimation of Salivary Parameters among Autoimmune Thyroiditis Patients.

PubMed

Syed, Yasmeen Amthul; Reddy, Bh Satheesh; Ramamurthy, T K; Rajendra, Kavitha; Nerella, Narendra Kumar; Krishnan, Meenakshi; Ramesh, M V; Mohammed, Rezwana Begum

2017-07-01

Saliva is a complex secretion that protects and lubricates the oral cavity. Various systemic diseases and their treatment alter the salivary gland function; one such disease is Autoimmune Thyroid Disease (AITD). AITD has been postulated to exert its hormonal influence on the salivary glands, leading to reduced salivary output. There's a paucity of literature, verifying the stated conjunction in human subjects. The aim was to investigate the salivary profile in AITD patients and its comparison with controls. Descriptive cross-sectional comparative study was conducted using convenience sampling method for screening the presence of thyroid disorders. Two groups comprising of 30 patients in each group diagnosed with autoimmune hypothyroiditis (n=30) and hyperthyroiditis (n=30) respectively and thirty healthy volunteers who were age and sex matched were included as controls. Saliva was collected and evaluated for Unstimulated Salivary Flow Rate (USSFR), pH and buffer capacity. ANOVA and Tukey post-hoc test was performed to find the statistical significance and for pairwise comparison. Statistically significant difference was observed between autoimmune hypothyroiditis, autoimmune hyperthyroiditis and control group with respect to USSFR (p<0.007), pH (p<0.001) and buffer capacity (p<0.001). On pairwise comparisons statistically significant difference was observed between autoimmune hypothyroiditis and autoimmune hyperthyroiditis with respect to controls. We conclude that significant involvement of salivary glands may occur in cases of AITD. Our study showed significant reduction of sialometric values in AITD patients when compared to controls. A strong clinical suspicion of thyroid diseases should be considered when there is chronic hyposalivation; hence thyroid profile must also be done, if the known causes have been excluded.

Estimation of Salivary Parameters among Autoimmune Thyroiditis Patients

PubMed Central

Reddy, BH Satheesh; Ramamurthy, TK; Rajendra, Kavitha; Nerella, Narendra Kumar; Krishnan, Meenakshi; Ramesh, MV; Mohammed, Rezwana Begum

2017-01-01

Introduction Saliva is a complex secretion that protects and lubricates the oral cavity. Various systemic diseases and their treatment alter the salivary gland function; one such disease is Autoimmune Thyroid Disease (AITD). AITD has been postulated to exert its hormonal influence on the salivary glands, leading to reduced salivary output. There’s a paucity of literature, verifying the stated conjunction in human subjects. Aim The aim was to investigate the salivary profile in AITD patients and its comparison with controls. Materials and Methods Descriptive cross-sectional comparative study was conducted using convenience sampling method for screening the presence of thyroid disorders. Two groups comprising of 30 patients in each group diagnosed with autoimmune hypothyroiditis (n=30) and hyperthyroiditis (n=30) respectively and thirty healthy volunteers who were age and sex matched were included as controls. Saliva was collected and evaluated for Unstimulated Salivary Flow Rate (USSFR), pH and buffer capacity. ANOVA and Tukey post-hoc test was performed to find the statistical significance and for pairwise comparison. Results Statistically significant difference was observed between autoimmune hypothyroiditis, autoimmune hyperthyroiditis and control group with respect to USSFR (p<0.007), pH (p<0.001) and buffer capacity (p<0.001). On pairwise comparisons statistically significant difference was observed between autoimmune hypothyroiditis and autoimmune hyperthyroiditis with respect to controls. Conclusion We conclude that significant involvement of salivary glands may occur in cases of AITD. Our study showed significant reduction of sialometric values in AITD patients when compared to controls. A strong clinical suspicion of thyroid diseases should be considered when there is chronic hyposalivation; hence thyroid profile must also be done, if the known causes have been excluded. PMID:28893031

Hypogonadism and the risk of rheumatic autoimmune disease

PubMed Central

Snih, Soham Al; Raji, Mukaila A.; Urban, Randall J.; Sharma, Gulshan; Sheffield-Moore, Melinda; Lopez, David S.; Baillargeon, Gwen; Kuo, Yong-Fang

2017-01-01

Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation’s largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms. PMID:27325124

Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM).

PubMed

Kakleas, Kostas; Soldatou, Alexandra; Karachaliou, Feneli; Karavanaki, Kyriaki

2015-09-01

Type 1 diabetes (T1DM) is an autoimmune disease with aberrant immune responses to specific β-cell autoantigens, resulting in insulin deficiency. Children and adolescents with T1DM may also develop organ-specific multiple autoimmunity in the context of APS (autoimmune polyendocrine syndrome) type 1, 2 or 3. The most frequently encountered associated autoimmune disorders in T1DM are autoimmune thyroid, followed by celiac, autoimmune gastric disease and other rare autoimmune conditions. There are limited previous studies on the prevalence of associated autoimmunity, especially multiple, in children with T1DM. The present review reports on the classification of autoimmune diabetes, and on the prevalence, pathogenesis, predictive factors and clinical presentation of pancreatic autoimmunity and of all associated autoimmune disorders in children with T1DM. The impact of associated autoimmunity on diabetes control and general health is also discussed, along with suggestions regarding screening strategies and follow-up for early detection and management of the autoimmunity. Copyright © 2015 Elsevier B.V. All rights reserved.

Myocarditis in auto-immune or auto-inflammatory diseases.

PubMed

Comarmond, Cloé; Cacoub, Patrice

2017-08-01

Myocarditis is a major cause of heart disease in young patients and a common precursor of heart failure due to dilated cardiomyopathy. Some auto-immune and/or auto-inflammatory diseases may be accompanied by myocarditis, such as sarcoidosis, Behçet's disease, eosinophilic granulomatosis with polyangiitis, myositis, and systemic lupus erythematosus. However, data concerning myocarditis in such auto-immune and/or auto-inflammatory diseases are sparse. New therapeutic strategies should better target the modulation of the immune system, depending on the phase of the disease and the type of underlying auto-immune and/or auto-inflammatory disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Immunotherapeutics in Pediatric Autoimmune Central Nervous System Disease: Agents and Mechanisms.

PubMed

Nosadini, Margherita; Sartori, Stefano; Sharma, Suvasini; Dale, Russell C

2017-08-01

Beyond the major advances produced by careful clinical-radiological phenotyping and biomarker development in autoimmune central nervous system disorders, a comprehensive knowledge of the range of available immune therapies and a deeper understanding of their action should benefit therapeutic decision-making. This review discusses the agents used in neuroimmunology and their mechanisms of action. First-line treatments typically include corticosteroids, intravenous immunoglobulin, and plasmapheresis, while for severe disease second-line "induction" agents such as rituximab or cyclophosphamide are used. Steroid-sparing agents such as mycophenolate, azathioprine, or methotrexate are often used in potentially relapsing or corticosteroid-dependent diseases. Lessons from adult neuroimmunology and rheumatology could be translated into pediatric autoimmune central nervous system disease in the future, including the potential utility of monoclonal antibodies targeting lymphocytes, adhesion molecules for lymphocytic migration, cytokines or their receptors, or complement. Finally, many agents used in other fields have multiple mechanisms of action, including immunomodulation, with potential usefulness in neuroimmunology, such as antibiotics, psychotropic drugs, probiotics, gut health, and ketogenic diet. All currently accepted and future potential agents have adverse effects, which can be severe; therefore, a "risk-versus-benefit" determination should guide therapeutic decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

Autoimmune post-herpes simplex encephalitis of adults and teenagers.

PubMed

Armangue, Thaís; Moris, Germán; Cantarín-Extremera, Verónica; Conde, Carlos Enrique; Rostasy, Kevin; Erro, Maria Elena; Portilla-Cuenca, Juan Carlos; Turón-Viñas, Eulàlia; Málaga, Ignacio; Muñoz-Cabello, Beatriz; Torres-Torres, Carmen; Llufriu, Sara; González-Gutiérrez-Solana, Luis; González, Guillermo; Casado-Naranjo, Ignacio; Rosenfeld, Myrna; Graus, Francesc; Dalmau, Josep

2015-11-17

To report 14 patients with immune-mediated relapsing symptoms post-herpes simplex encephalitis (HSE) and to compare the clinical and immunologic features of the teenage and adult group with those of young children. Prospective observational study of patients diagnosed between June 2013 and February 2015. Immunologic techniques have been reported previously. Among the teenage and adult group (8 patients, median age 40 years, range 13-69; 5 male), 3 had an acute symptom presentation suggesting a viral relapse, and 5 a presentation contiguous with HSE suggesting a recrudescence of previous deficits. Seven patients developed severe psychiatric/behavioral symptoms disrupting all social interactions, and one refractory status epilepticus. Blepharospasm occurred in one patient. Five patients had CSF antibodies against NMDA receptor (NMDAR) and 3 against unknown neuronal cell surface proteins. In 5/6 patients, the brain MRI showed new areas of contrast enhancement that decreased after immunotherapy and clinical improvement. Immunotherapy was useful in 7/7 patients, sometimes with impressive recoveries, returning to their baseline HSE residual deficits. Compared with the 6 younger children (median age 13 months, range 6-20, all with NMDAR antibodies), the teenagers and adults were less likely to develop choreoathetosis (0/8 vs 6/6, p < 0.01) and decreased level of consciousness (2/8 vs 6/6, p < 0.01) and had longer delays in diagnosis and treatment (interval relapse/antibody testing 85 days, range 17-296, vs 4 days, range 0-33, p = 0.037). In teenagers and adults, the immune-mediated relapsing syndrome post-HSE is different from that known in young children as choreoathetosis post-HSE and is underrecognized. Prompt diagnosis is important because immunotherapy can be highly effective. © 2015 American Academy of Neurology.

[A case of anti-LKM 1 positive autoimmune hepatitis accompanied by systemic lupus erythematosus].

PubMed

Choi, Dae Han; Kim, Hae Kyung; Park, Tae Il; John, Byung Min; Kang, Sung Hwan; Lee, Yoon Serk; Kim, Tae Hyun; Lee, Uh Joo; Lee, Tae Seung; Yoon, Gwi Ok

2008-03-01

Overlap of autoimmune hepatitis and systemic lupus erythematosus (SLE) is a comparatively rare condition. Although both autoimmune hepatitis and SLE can share common autoimmune features such as polyarthralgia, hypergammaglobulinemia and positive ANA, it has been considered as two different entities. We report a case of anti-LKM1 positive autoimmune hepatitis who developed SLE two years later. The presence of interface hepatitis with lymphoplasma cell infiltrates and rosette formation points to the autoimmune hepatitis rather than SLE hepatitis. Autoimmune hepatitis is infrequently accompanied by SLE, therefore, it could be recommended to investigate for SLE in patients with autoimmune hepatitis.

Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus

PubMed Central

Brooks, Wesley H.; Renaudineau, Yves

2015-01-01

Autoimmune diseases occur more often in females, suggesting a key role for the X chromosome. X chromosome inactivation, a major epigenetic feature in female cells that provides dosage compensation of X-linked genes to avoid overexpression, presents special vulnerabilities that can contribute to the disease process. Disruption of X inactivation can result in loss of dosage compensation with expression from previously sequestered genes, imbalance of gene products, and altered endogenous material out of normal epigenetic context. In addition, the human X has significant differences compared to other species and these differences can contribute to the frequency and intensity of the autoimmune disease in humans as well as the types of autoantigens encountered. Here a link is demonstrated between autoimmune diseases, such as systemic lupus erythematosus, and the X chromosome by discussing cases in which typically non-autoimmune disorders complicated with X chromosome abnormalities also present lupus-like symptoms. The discussion is then extended to the reported spatial and temporal associations of the inactive X chromosome with the nucleolus. When frequent episodes of cellular stress occur, the inactive X chromosome may be disrupted and inadvertently become involved in the nucleolar stress response. Development of autoantigens, many of which are at least transiently components of the nucleolus, is then described. Polyamines, which aid in nucleoprotein complex assembly in the nucleolus, increase further during cell stress, and appear to have an important role in the autoimmune disease process. Autoantigenic endogenous material can potentially be stabilized by polyamines. This presents a new paradigm for autoimmune diseases: that many are antigen-driven and the autoantigens originate from altered endogenous material due to episodes of cellular stress that disrupt epigenetic control. This suggests that epigenetics and the X chromosome are important aspects of autoimmune

[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%).

[Autoimmune polyglandular syndrome type 2 in pregnancy: a case report].

PubMed

Krysiak, Robert; Okopień, Bogusław

2013-01-01

Autoimmune polyglandular syndromes are conditions characterized by the association of two or more organ-specific disorders. On the basis of the clinical picture, they are divided into four different types. If undiagnosed and untreated, autoimmune polyglandular syndromes may pose a serious risk to patients. We report here a case of a pregnant woman with autoimmune polyglandular syndrome type 2. She was diagnosed with Addison's disease 11 months before the onset of the pregnancy and until the end of the first trimester the disease was effectively controlled by hydrocortisone and fludrocortisone treatment. In the tenth week of gestation, the patient developed Graves' disease and the treatment with propylthiouracil was started treatment leading to the unmasking of adrenal insufficiency, which required titration of hydrocortisone dose. Our study shows that autoimmune polyglandular syndromes should be considered in every pregnant woman with any autoimmune endocrine disease and that the treatment of these syndromes during gestation may be challenging.

Diego and Giorgina Vergani: The two hearts of translational autoimmunity.

PubMed

Liberal, Rodrigo; Selmi, Carlo; Gershwin, M Eric

2016-01-01

Since the publication of the first textbook on autoimmune diseases in 1963, the knowledge in the field has exponentially grown into numerous tracks of research, particularly at benchside. Systemic and organ-specific autoimmune diseases, as in the case of the liver, have witnessed notable advances in terms of epidemiology, genetics, effector and regulatory mechanisms, and ultimately treatment. While the available tools for communication have provided accelerating progress rates, we recognize that key opinion leaders continue to provide significant contributions to the field. The present issue is dedicated to celebrate Giorgina Mieli-Vergani and Diego Vergani as two of the finest examples of excellence in autoimmune liver diseases and the broader field of autoimmunity. Diego and Giorgina are extremely well-liked Colleagues who fully represent the translational efforts between laboratory research and clinically relevant questions in the practice of pediatric liver diseases and autoimmune hepatitis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chromosomal Gains at 9q Characterize Enteropathy-Type T-Cell Lymphoma

PubMed Central

Zettl, Andreas; Ott, German; Makulik, Angela; Katzenberger, Tiemo; Starostik, Petr; Eichler, Thorsten; Puppe, Bernhard; Bentz, Martin; Müller-Hermelink, Hans Konrad; Chott, Andreas

2002-01-01

Genetic alterations in enteropathy-type T-cell lymphoma (ETL) are unknown so far. In this series, 38 cases of ETL were analyzed by comparative genomic hybridization (CGH). CGH revealed chromosomal imbalances in 87% of cases analyzed, with recurrent gains of genetic material involving chromosomes 9q (in 58% of cases), 7q (24%), 5q (18%), and 1q (16%). Recurrent losses of genetic material occurred on chromosomes 8p and 13q (24% each), and 9p (18%). In this first systematic genetic study on ETL, chromosomal gains on 9q (minimal overlapping region 9q33-q34) were found to be highly characteristic of ETL. Fluorescence in situ hybridization analysis on four cases of ETL, using a probe for 9q34, indicated frequent and multiple gains of chromosomal material at 9q34 (up to nine signals per case). Among 16 patients with ETL who survived initial disease presentation, patients with more than three chromosomal gains or losses (n = 11) followed a worse clinical course than those with three or less imbalances (n = 5). The observation of similar genetic alterations in ETL and in primary gastric (n = 4) and colonic (n = 1) T-cell lymphoma, not otherwise specified, is suggestive of a genetic relationship of gastrointestinal T-cell lymphomas at either localization. PMID:12414511

Immune cell populations within the duodenal mucosa of dogs with enteropathies.

PubMed

German, A J; Hall, E J; Day, M J

2001-01-01

The mucosal immune system may play a critical role in the pathogenesis of small intestinal enteropathies. The aim of the current study was to assess mucosal immune cell populations in dogs with inflammatory bowel disease (IBD), idiopathic antibiotic-responsive diarrhea (ARD), and adverse reactions to food (FR). Endoscopic biopsies were performed of the duodenum of dogs with these conditions and from a group of dogs without enteric disease. Additional control samples were collected after death from other dogs that did not have evidence of enteric disease. Immunohistochemistry and computer-aided morphometry were used to assess the distribution of immune cell subsets in both lamina propria and intestinal epithelium. Compared with controls, dogs with ARD had increased numbers of lamina propria immunoglobulin (Ig) A- plasma cells and CD4+ cells. More marked alterations were noted in dogs with IBD, with significant increases in lamina propria IgG+ plasma cells, T cells (CD3+), CD4+ cells, macrophages, and neutrophils, but with reduced mast cell numbers. Increased intraepithelial CD3+ T cells were also present in the dogs with IBD, compared with controls. However, lamina propria and epithelial populations were unaltered in dogs with FR when compared with controls. The altered mucosal immune cell populations observed in dogs with ARD or IBD may reflect an underlying immunologic pathogenesis in these disorders.

High SMAD7 and p-SMAD2,3 expression is associated with environmental enteropathy in children.

PubMed

Syed, Sana; Dinallo, Vincenzo; Iqbal, Najeeha T; Di Iorio, Laura; Di Fusco, Davide; Guleria, Shan; Amadi, Beatrice C; Sadiq, Kamran; Moskaluk, Christopher; Ali, S Asad; Kelly, Paul; Monteleone, Giovanni

2018-02-01

Enteropathies such as Crohn's disease are associated with enteric inflammation characterized by impaired TGF-β signaling, decreased expression of phosphorylated (p)-SMAD2,3 and increased expression of SMAD7 (an inhibitor of SMAD3 phosphorylation). Environmental enteropathy (EE) is an acquired inflammatory disease of the small intestine (SI), which is associated with linear growth disruption, cognitive deficits, and reduced oral vaccine responsiveness in children <5 y in resource-poor countries. We aimed to characterize EE inflammatory pathways by determining SMAD7 and p-SMAD2,3 levels (using Western blotting) in EE duodenal biopsies (N = 19 children, 7 from Pakistan, 12 from Zambia) and comparing these with healthy controls (Ctl) and celiac disease (CD) patients from Italy. Densitometric analysis of immunoblots showed that EE SI biopsies expressed higher levels of both SMAD7 (mean±SD in arbitrary units [a.u.], Ctl = 0.47±0.20 a.u., EE = 1.13±0.25 a.u., p-value = 0.03) and p-SMAD2,3 (mean±SD, Ctl = 0.38±0.14 a.u., EE = 0.60±0.10 a.u., p-value = 0.03). Immunohistochemistry showed that, in EE, SMAD7 is expressed in both the epithelium and in mononuclear cells of the lamina propria (LP). In contrast, p-SMAD3 in EE is expressed much more prominently in epithelial cells than in the LP. The high SMAD7 immunoreactivity and lack of p-SMAD3 expression in the LP suggests defective TGF-β signaling in the LP in EE similar to a previously reported SMAD7-mediated inflammatory pathway in refractory CD and Crohn's disease. However, Western blot densitometry showed elevated p-SMAD2,3 levels in EE, possibly suggesting a different inflammatory pathway than Crohn's disease but more likely reflecting cumulative protein expression from across all compartments of the mucosa as opposed to the LP alone. Further studies are needed to substantiate these preliminary results and to illustrate the relationship between SMAD proteins, TGF-β signaling, and inflammatory cytokine production

Real-time shear wave elastography may predict autoimmune thyroid disease.

PubMed

Vlad, Mihaela; Golu, Ioana; Bota, Simona; Vlad, Adrian; Timar, Bogdan; Timar, Romulus; Sporea, Ioan

2015-05-01

To evaluate and compare the values of the elasticity index as measured by shear wave elastography in healthy subjects and in patients with autoimmune thyroid disease, in order to establish if this investigation can predict the occurrence of autoimmune thyroid disease. A total of 104 cases were included in the study group: 91 women (87.5%), out of which 52 (50%) with autoimmune thyroid disease diagnosed by specific tests and 52 (50%) healthy volunteers, matched for age and gender. For all the subjects, three measurements were performed on each thyroid lobe and a mean value was calculated. The data were expressed in kPa. The investigation was performed with an Aixplorer system (SuperSonic Imagine, France), using a linear high-resolution 15-4 MHz transducer. The mean value for the elasticity index was similar in the right and the left thyroid lobes, both in normal subjects and in patients with autoimmune thyroid disease: 19.6 ± 6.6 vs. 19.5 ± 6.8 kPa, p = 0.92, and 26.6 ± 10.0 vs. 25.8 ± 11.7 kPa, p = 0.71, respectively. This parameter was significantly higher in patients with autoimmune thyroid disease than in controls (p < 0.001). For a cut-off value of 22.3 kPa, which resulted in the highest sum of sensitivity and specificity, the elasticity index assessed by shear wave elastography had a sensitivity of 59.6% and a specificity of 76.9% (AUROC = 0.71; p < 0.001) for predicting the presence of autoimmune thyroid disease. Quantitative elasticity index measured by shear wave elastography was significantly higher in autoimmune thyroid disease than in normal thyroid parenchyma and may predict the presence of autoimmune thyroid disease.

Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease

PubMed Central

Hasham, Muneer G.; Baxan, Nicoleta; Stuckey, Daniel J.; Branca, Jane; Perkins, Bryant; Dent, Oliver; Duffy, Ted; Hameed, Tolani S.; Stella, Sarah E.; Bellahcene, Mohammed; Schneider, Michael D.; Harding, Sian E.; Rosenthal, Nadia

2017-01-01

ABSTRACT Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity. PMID:28250051

Antineutrophil Cytoplasmic Antibodies, Autoimmune Neutropenia, and Vasculitis

PubMed Central

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

2011-01-01

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

[Maternal autoimmune thyroid disease: relevance for the newborn].

PubMed

Temboury Molina, M Carmen; Rivero Martín, M José; de Juan Ruiz, Jesús; Ares Segura, Susana

2015-04-08

Autoimmune thyroid disease is amongst the most frequent endocrine disorders during pregnancy. It is associated with an increase in perinatal morbidity, congenital defects, neurological damage, fetal and neonatal thyroid dysfunction. Maternal thyroid hormones play a key role in child neurodevelopment. We aimed to evaluate the thyroid function and the clinical course of neonates born from mothers with autoimmune thyroid disease during the first months of life in order to define the follow-up. We monitored thyroid function and clinical status during the first months in 81 newborns of mothers with autoimmune thyroid disease; 16 had Graves disease and 65 autoimmune thyroiditis. A percentage of 4.93 newborns had congenital defects, and 8.64% neonates showed an increase in thyrotropin (TSH) (>9.5 μUI/mL 2 times) and required thyroxin within the first month of life. A 85.7% of these showed a negative newborn screening (due to a later increase of TSH). A higher TSH value in the newborn was related to an older age of the mother, higher levels of thyroid peroxidase (TPO) antibody during pregnancy and lower birth weight. A higher free thyroxine (FT4) value in the newborn was related to fewer days of life and mothers with Graves disease. We recommend the evaluation of TSH, T4 and TPO antibodies before 10 weeks in all pregnant women with follow-up if maternal thyroid autoimmunity or disorders is detected. It is also recommended to test children's serum TSH and FT4 at 48 h of life in newborns of mothers with autoimmune thyroid disease and repeat them between the 2nd and 4th week in children with TSH>6 μUI/mL. Careful endocrine follow-up is advised in pregnant women and children if hyperthyroidism is detected. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Hypogonadism and the risk of rheumatic autoimmune disease.

PubMed

Baillargeon, Jacques; Al Snih, Soham; Raji, Mukaila A; Urban, Randall J; Sharma, Gulshan; Sheffield-Moore, Melinda; Lopez, David S; Baillargeon, Gwen; Kuo, Yong-Fang

2016-12-01

Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation's largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms.

AIRE: a missing link to explain female susceptibility to autoimmune diseases.

PubMed

Berrih-Aknin, Sonia; Panse, Rozen Le; Dragin, Nadine

2018-01-01

Women are more susceptible to autoimmune diseases than men. Autoimmunity results from tolerance breakdown toward self-components. Recently, three transcription modulators were identified in medullary thymic epithelial cells that orchestrate immune central tolerance processes: the autoimmune regulator (AIRE), FEZ family zinc finger 2 (FEZF2 or FEZ1), and PR domain zinc finger protein 1 (PRDM1). Interestingly, these three transcription modulators regulate nonredundant tissue-specific antigen subsets and thus cover broad antigen diversity. Recent data from different groups demonstrated that sex hormones (estrogen and testosterone) are involved in the regulation of thymic AIRE expression in humans and mice through direct transcriptional modulation and epigenetic changes. As a consequence, AIRE displays gender-biased thymic expression, with females showing a lower expression compared with males, a finding that could explain the female susceptibility to autoimmune diseases. So far, FEZF2 has not been related to an increased gender bias in autoimmune disease. PRDM1 expression has not been shown to display gender-differential thymic expression, but its expression level and its gene polymorphisms are associated with female-dependent autoimmune disease risk. Altogether, various studies have demonstrated that increased female susceptibility to autoimmune diseases is in part a consequence of hormone-driven reduced thymic AIRE expression. © 2017 New York Academy of Sciences.

Autoimmune neuroretinopathy secondary to Zika virus infection.

PubMed

Burgueño-Montañés, C; Álvarez-Coronado, M; Colunga-Cueva, M

2018-04-29

A 40-year-old woman diagnosed with Zika virus infection 6 months before she arrived at this hospital. She referred to a progressive and painless vision loss, of 2 weeks onset after the infection diagnosis. She was treated with topical steroids. Previous visual acuity was recovered, but she still refers to reduced visual field and nyctalopia. Ophthalmologic examination revealed severe retinal sequels, compatible with autoimmune retinopathy. Based on the clinical features and the temporal relationship with Zika virus infection, non-para-neoplastic autoimmune retinopathy was diagnosed and managed with steroids and infliximab. Zika virus can trigger a non-para-neoplastic autoimmune retinopathy. The diagnosis is based on clinical features, and requires early immunosuppressive therapy. Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Subclasses of immunoglobulins and autoantibodies in autoimmune diseases.

PubMed

Outschoorn, I; Rowley, M J; Cook, A D; Mackay, I R

1993-01-01

The differing capacity of subclasses of IgG to bind to protein A and protein G was used in a sequential affinity purification procedure to examine immunoglobulin isotypes and subclasses in autoimmune disease. The utility of the procedure is that affinity-purified fractions containing particular isotypes and subclasses of immunoglobulin can be analyzed for their content of autoantibodies using standard techniques. For each of four autoimmune diseases studied, chronic active hepatitis, Sjogren's syndrome, primary biliary cirrhosis, and rheumatoid arthritis, there were characteristic protein elution profiles and the various disease-specific autoantibodies showed preferential distributions among the isotypes and subclasses. Moreover there was not an absolute correlation between an increased level of a particular subclass and the occurrence of antibodies of that subclass. The occurrence of highly disease-specific immunoglobulin subclass profiles suggests that the hypergammaglobulinemia associated with autoimmunity cannot be attributed entirely to polyclonal B-cell activation. Rather, there are disease-specific alterations in isotype subclass switching which may reflect different cytokine-dependent influences on autoimmune B cells and their products.

The clinical spectrum of autoimmune congenital heart block

PubMed Central

Brito-Zerón, Pilar; Izmirly, Peter M.; Ramos-Casals, Manuel; Buyon, Jill P.; Khamashta, Munther A.

2017-01-01

Autoimmune congenital heart block (CHB) is an immune-mediated acquired disease that is associated with the placental transference of maternal antibodies specific for Ro and La autoantigens. The disease develops in a fetal heart without anatomical abnormalities that could otherwise explain the block, and which is usually diagnosed in utero, but also at birth or within the neonatal period. Autoantibody-mediated damage of fetal conduction tissues causes inflammation and fibrosis and leads to blockage of signal conduction at the atrioventricular (AV) node. Irreversible complete AV block is the principal cardiac manifestation of CHB, although some babies might develop other severe cardiac complications, such as endocardial fibroelastosis or valvular insufficiency, even in the absence of cardiac block. In this Review, we discuss the epidemiology, classification and management of women whose pregnancies are affected by autoimmune CHB, with a particular focus on the autoantibodies associated with autoimmune CHB and how we should test for these antibodies and diagnose this disease. Without confirmed effective preventive or therapeutic strategies and further research on the aetiopathogenic mechanisms, autoimmune CHB will remain a severe life-threatening disorder. PMID:25800217

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.

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

Autoimmune Thyroiditis and Myasthenia Gravis

PubMed Central

Lopomo, Angela; Berrih-Aknin, Sonia

2017-01-01

Autoimmune diseases (AIDs) are the result of specific immune responses directed against structures of the self. In normal conditions, the molecules recognized as “self” are tolerated by immune system, but when the self-tolerance is lost, the immune system could react against molecules from the body, causing the loss of self-tolerance, and subsequently the onset of AID that differs for organ target and etiology. Autoimmune thyroid disease (ATD) is caused by the development of autoimmunity against thyroid antigens and comprises Hashimoto’s thyroiditis and Graves disease. They are frequently associated with other organ or non-organ specific AIDs, such as myasthenia gravis (MG). In fact, ATD seems to be the most associated pathology to MG. The etiology of both diseases is multifactorial and it is due to genetic and environmental factors, and each of them has specific characteristics. The two pathologies show many commonalities, such as the organ-specificity with a clear pathogenic effect of antibodies, the pathological mechanisms, such as deregulation of the immune system and the implication of the genetic predisposition. They also show some differences, such as the mode of action of the antibodies and therapies. In this review that focuses on ATD and MG, the common features and the differences between the two diseases are discussed. PMID:28751878

Restoration of the type I IFN–IL-1 balance through targeted blockade of PTGER4 inhibits autoimmunity in NOD mice

PubMed Central

Rahman, M. Jubayer; Quiel, Juan A.; Liu, Yi; Bhargava, Vipul; Zhao, Yongge; Hotta-Iwamura, Chie; Lau-Kilby, Annie W.; Malloy, Allison M.W.; Thoner, Timothy W.; Tarbell, Kristin V.

2018-01-01

Type I IFN (IFN-I) dysregulation contributes to type 1 diabetes (T1D) development, and although increased IFN-I signals are pathogenic at the initiation of autoimmune diabetes, IFN-I dysregulation at later pathogenic stages more relevant for therapeutic intervention is not well understood. We discovered that 5 key antigen-presenting cell subsets from adult prediabetic NOD mice have reduced responsiveness to IFN-I that is dominated by a decrease in the tonic-sensitive subset of IFN-I response genes. Blockade of IFNAR1 in prediabetic NOD mice accelerated diabetes and increased Th1 responses. Therefore, IFN-I responses shift from pathogenic to protective as autoimmunity progresses, consistent with chronic IFN-I exposure. In contrast, IL-1–associated inflammatory pathways were elevated in prediabetic mice. These changes correlated with human T1D onset-associated gene expression. Prostaglandin E2 (PGE2) and prostaglandin receptor 4 (PTGER4), a receptor for PGE2 that mediates both inflammatory and regulatory eicosanoid signaling, were higher in NOD mice and drive innate immune dysregulation. Treating prediabetic NOD mice with a PTGER4 antagonist restored IFNAR signaling, decreased IL-1 signaling, and decreased infiltration of leukocytes into the islets. Therefore, innate cytokine alterations contribute to both T1D-associated inflammation and autoimmune pathogenesis. Modulating innate immune balance via signals such as PTGER4 may contribute to treatments for autoimmunity. PMID:29415894

Restoration of the type I IFN-IL-1 balance through targeted blockade of PTGER4 inhibits autoimmunity in NOD mice.

PubMed

Rahman, M Jubayer; Rodrigues, Kameron B; Quiel, Juan A; Liu, Yi; Bhargava, Vipul; Zhao, Yongge; Hotta-Iwamura, Chie; Shih, Han-Yu; Lau-Kilby, Annie W; Malloy, Allison Mw; Thoner, Timothy W; Tarbell, Kristin V

2018-02-08

Type I IFN (IFN-I) dysregulation contributes to type 1 diabetes (T1D) development, and although increased IFN-I signals are pathogenic at the initiation of autoimmune diabetes, IFN-I dysregulation at later pathogenic stages more relevant for therapeutic intervention is not well understood. We discovered that 5 key antigen-presenting cell subsets from adult prediabetic NOD mice have reduced responsiveness to IFN-I that is dominated by a decrease in the tonic-sensitive subset of IFN-I response genes. Blockade of IFNAR1 in prediabetic NOD mice accelerated diabetes and increased Th1 responses. Therefore, IFN-I responses shift from pathogenic to protective as autoimmunity progresses, consistent with chronic IFN-I exposure. In contrast, IL-1-associated inflammatory pathways were elevated in prediabetic mice. These changes correlated with human T1D onset-associated gene expression. Prostaglandin E2 (PGE2) and prostaglandin receptor 4 (PTGER4), a receptor for PGE2 that mediates both inflammatory and regulatory eicosanoid signaling, were higher in NOD mice and drive innate immune dysregulation. Treating prediabetic NOD mice with a PTGER4 antagonist restored IFNAR signaling, decreased IL-1 signaling, and decreased infiltration of leukocytes into the islets. Therefore, innate cytokine alterations contribute to both T1D-associated inflammation and autoimmune pathogenesis. Modulating innate immune balance via signals such as PTGER4 may contribute to treatments for autoimmunity.

Mitochondrial enteropathy: the primary pathology may not be within the gastrointestinal tract

PubMed Central

Chinnery, P; Jones, S; Sviland, L; Andrews, R; Parsons, T; Turnbull, D; Bindoff, L

2001-01-01

BACKGROUND—Mitochondrial DNA (mtDNA) defects are an important cause of disease. Although gastrointestinal symptoms are common in these patients, their pathogenesis remains uncertain.
AIM—To investigate the role of the mtDNA defect in the production of gastrointestinal dysfunction.
PATIENT—A 20 year old woman who presented at 15 years of age with recurrent vomiting and pseudo-obstruction, who did not respond to conservative management and ultimately had subtotal gastrectomy and Roux-en-y reconstruction. She subsequently presented with status epilepticus and was found to have a mitochondrial respiratory chain disorder due to a pathogenic mtDNA point mutation (A3243G).
METHODS—Resected bowel was studied using light and electron microscopy and mtDNA analysed from both mucosal and muscular layers using polymerase chain reaction generated RFLP analysis. 
RESULTS— Histological and electron microscopic studies revealed no morphological abnormalities in the resected stomach, and molecular genetic analysis failed to identify the genetic defect in either the mucosal or muscle layers.
CONCLUSION—This study suggests that in some individuals with gastrointestinal symptoms associated with established mitochondrial DNA disease, the primary pathology of the mitochondrial enteropathy lies outside the gastrointestinal tract.


Keywords: mitochondrial encephalomyopathy; cyclical vomiting; pseudo-obstruction PMID:11115833

HIV enteropathy and aging: gastrointestinal immunity, mucosal epithelial barrier, and microbial translocation.

PubMed

Wang, Hongyin; Kotler, Donald P

2014-07-01

Despite decreases in morbidity and mortality as a result of antiretroviral therapy, gastrointestinal dysfunction remains common in HIV infection. Treated patients are at risk for complications of 'premature' aging, such as cardiovascular disease, osteopenia, neurocognitive decline, malignancies, and frailty. This review summarizes recent observations in this field. Mucosal CD4 lymphocytes, especially Th17 cells, are depleted in acute HIV and simian immune deficiency virus (SIV) infections, although other cell types also are affected. Reconstitution during therapy often is incomplete, especially in mucosa. Mucosal barrier function is affected by both HIV infection and aging and includes paracellular transport via tight junctions and uptake through areas of apoptosis; other factors may affect systemic antigen exposure. The resultant microbial translocation is associated with systemic immune activation in HIV and SIV infections. There is evidence of immune activation and microbial translocation in the elderly. The immune phenotypes of immunosenescence in HIV infection and aging appear similar. There are several targets for intervention; blockage of residual mucosal virus replication, preventing antigen uptake, modulating the microbiome, improving T cell recovery, combining therapies aimed at mucosal integrity, augmenting mucosal immunity, and managing traditional risk factors for premature aging in the general population. Aging may interact with HIV enteropathy to enhance microbial translocation and immune activation.

Differences between older and young patients with autoimmune gastritis.

PubMed

Kalkan, Çağdaş; Soykan, Irfan

2017-07-01

Elderly patients with autoimmune gastritis might have different symptoms than those of young patients. The aim of the present study was to compare presented symptoms and laboratory parameters associated with autoimmune gastritis in both old and young age groups. A total of 355 patients with autoimmune gastritis were stratified into two groups: 65 years or older (n = 119, mean age 69.47 ± 5.027 years), and under 65 years (n = 236, mean age 45.79 ± 10.51 years). These two groups were then evaluated and compared by means of clinical symptoms, concurrent autoimmune diseases, serum gastrin, vitamin B 12 and chromogranin A levels, and the presence of enterochromograffin-like cell hyperplasia. Among 119 older patients, 35 had dyspeptic symptoms, and 84 patients were referred for vitamin B 12 and/or iron deficiency. In the younger group (n = 236), there were more patients who had dyspeptic symptoms (36 vs 200, P < 0.001). Serum gastrin (726.68 ± 266.183 vs 214.36 ± 104.62 pg/mL, P < 0.001) and chromogranin A (301.26 ± 172.95 vs 106.59 ± 67.66 ng/mL, P < 0.001) levels were significantly higher, and the presence of enterochromograffin-like cell hyperplasia was more frequent (113 vs 31, P < 0.001) in older patients than younger patients. Polyautoimmunity (66.3% vs 24.5%) and multiple autoimmune syndrome (17.6% vs 5.5%) were more common in older patients (P < 0.001). There are differences in the clinical characteristics and the laboratory parameters between patients with autoimmune gastritis that are older and younger than 65 years-of-age. Elderly patients with autoimmune gastritis were investigated more commonly for vitamin B 12 and/or iron deficiency. Polyautoimmunity and multiple autoimmune syndrome were more common, and serum gastrin and chromogranin A levels were significantly higher in older patients. Geriatr Gerontol Int 2017; 17: 1090-1095. © 2016 Japan Geriatrics Society.

[Treatment and results of therapy in autoimmune hemolytic anemia].

PubMed

Tasić, J; Macukanović, L; Pavlović, M; Koraćević, S; Govedarević, N; Kitić, Lj; Tijanić, I; Bakić, M

1994-01-01

Basic principles in the therapy of idiopathic autoimmune hemolytic anemia induced by warm antibody were glucocorticoides and splenectomy. Immunosupresive drugs, plasmaferesis and intravenous high doses gamma globulin therapy are also useful. In secundary autoimmune hemolytic anemia induced by warm antibody we treated basic illness. During the period of 1990-1992 we treated 21 patients with primary autoimmune hemolytic anemia and 6 patients with secondary /4 CLL and 2 Non-Hodgkin's lymphoma/. Complete remission we found as a normalisation of reticulocites and hemoglobin level respectively. Complete remission by corticoides we got in 14/21 patients, partial response in 2/21 respectively. Complete response by splenectomy we got in 2/3 splenoctomized patients (idiopathic type). For successful treatment secondary hemolytic anemias we treated primary diseases (CLL and malignant lymphoma) and we got in 4/6 patients complete remission. Our results were standard in both type of autoimmune hemolytic anaemias induced by warm antibody.

Biomarkers of Environmental Enteropathy are Positively Associated with Immune Responses to an Oral Cholera Vaccine in Bangladeshi Children

PubMed Central

Uddin, Muhammad Ikhtear; Islam, Shahidul; Nishat, Naoshin S.; Hossain, Motaher; Rafique, Tanzeem Ahmed; Rashu, Rasheduzzaman; Hoq, Mohammad Rubel; Zhang, Yue; Saha, Amit; Harris, Jason B.; Calderwood, Stephen B.; Bhuiyan, Taufiqur Rahman; Ryan, Edward T.; Leung, Daniel T.; Qadri, Firdausi

2016-01-01

Environmental enteropathy (EE) is a poorly understood condition that refers to chronic alterations in intestinal permeability, absorption, and inflammation, which mainly affects young children in resource-limited settings. Recently, EE has been linked to suboptimal oral vaccine responses in children, although immunological mechanisms are poorly defined. The objective of this study was to determine host factors associated with immune responses to an oral cholera vaccine (OCV). We measured antibody and memory T cell immune responses to cholera antigens, micronutrient markers in blood, and EE markers in blood and stool from 40 Bangladeshi children aged 3–14 years who received two doses of OCV given 14 days apart. EE markers included stool myeloperoxidase (MPO) and alpha anti-trypsin (AAT), and plasma endotoxin core antibody (EndoCab), intestinal fatty acid binding protein (i-FABP), and soluble CD14 (sCD14). We used multiple linear regression analysis with LASSO regularization to identify host factors, including EE markers, micronutrient (nutritional) status, age, and HAZ score, predictive for each response of interest. We found stool MPO to be positively associated with IgG antibody responses to the B subunit of cholera toxin (P = 0.03) and IgA responses to LPS (P = 0.02); plasma sCD14 to be positively associated with LPS IgG responses (P = 0.07); plasma i-FABP to be positively associated with LPS IgG responses (P = 0.01) and with memory T cell responses specific to cholera toxin (P = 0.01); stool AAT to be negatively associated with IL-10 (regulatory) T cell responses specific to cholera toxin (P = 0.02), and plasma EndoCab to be negatively associated with cholera toxin-specific memory T cell responses (P = 0.02). In summary, in a cohort of children 3–14 years old, we demonstrated that the majority of biomarkers of environmental enteropathy were positively associated with immune responses after vaccination with an OCV. PMID:27824883

Biomarkers of Environmental Enteropathy are Positively Associated with Immune Responses to an Oral Cholera Vaccine in Bangladeshi Children.

PubMed

Uddin, Muhammad Ikhtear; Islam, Shahidul; Nishat, Naoshin S; Hossain, Motaher; Rafique, Tanzeem Ahmed; Rashu, Rasheduzzaman; Hoq, Mohammad Rubel; Zhang, Yue; Saha, Amit; Harris, Jason B; Calderwood, Stephen B; Bhuiyan, Taufiqur Rahman; Ryan, Edward T; Leung, Daniel T; Qadri, Firdausi

2016-11-01

Environmental enteropathy (EE) is a poorly understood condition that refers to chronic alterations in intestinal permeability, absorption, and inflammation, which mainly affects young children in resource-limited settings. Recently, EE has been linked to suboptimal oral vaccine responses in children, although immunological mechanisms are poorly defined. The objective of this study was to determine host factors associated with immune responses to an oral cholera vaccine (OCV). We measured antibody and memory T cell immune responses to cholera antigens, micronutrient markers in blood, and EE markers in blood and stool from 40 Bangladeshi children aged 3-14 years who received two doses of OCV given 14 days apart. EE markers included stool myeloperoxidase (MPO) and alpha anti-trypsin (AAT), and plasma endotoxin core antibody (EndoCab), intestinal fatty acid binding protein (i-FABP), and soluble CD14 (sCD14). We used multiple linear regression analysis with LASSO regularization to identify host factors, including EE markers, micronutrient (nutritional) status, age, and HAZ score, predictive for each response of interest. We found stool MPO to be positively associated with IgG antibody responses to the B subunit of cholera toxin (P = 0.03) and IgA responses to LPS (P = 0.02); plasma sCD14 to be positively associated with LPS IgG responses (P = 0.07); plasma i-FABP to be positively associated with LPS IgG responses (P = 0.01) and with memory T cell responses specific to cholera toxin (P = 0.01); stool AAT to be negatively associated with IL-10 (regulatory) T cell responses specific to cholera toxin (P = 0.02), and plasma EndoCab to be negatively associated with cholera toxin-specific memory T cell responses (P = 0.02). In summary, in a cohort of children 3-14 years old, we demonstrated that the majority of biomarkers of environmental enteropathy were positively associated with immune responses after vaccination with an OCV.

Diabetic peripheral neuropathy, is it an autoimmune disease?

PubMed

Janahi, Noor M; Santos, Derek; Blyth, Christine; Bakhiet, Moiz; Ellis, Mairghread

2015-11-01

Autoimmunity has been identified in a significant number of neuropathies, such as, proximal neuropathies, and autonomic neuropathies associated with diabetes mellitus. However, possible correlations between diabetic peripheral neuropathy and autoimmunity have not yet been fully investigated. This study was conducted to investigate whether autoimmunity is associated with the pathogenesis of human diabetic peripheral neuropathy. A case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 diabetic control patients without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the percentages of positive antinuclear antibodies (ANA) between the three groups. Secondary analysis investigated the correlations between the presence of autoimmune antibodies and sample demographics and neurological manifestations. This research was considered as a pilot study encouraging further investigations to take place in the near future. Antinuclear antibodies were significantly present in the blood serum of patients with diabetic peripheral neuropathy in comparison to the control groups (p<0.001). The odds of positive values of ANA in the neuropathy group were 50 times higher when compared to control groups. Secondary analysis showed a significant correlation between the presence of ANA and the neurological manifestation of neuropathy (Neuropathy symptom score, Neuropathy disability score and Vibration Perception Threshold). The study demonstrated for the first time that human peripheral diabetic neuropathy may have an autoimmune aetiology. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers. Copyright © 2015 Elsevier B.V. All rights reserved.

[Autoimmune/infl ammatory syndrome induced by adjuvants, ASIA].

PubMed

Stolarczyk, Jędrzej; Kubiś, Marek; Brzosko, Marek

There have been many cases of the appearance of autoantibodies and symptoms of disease after exposure to adjuvants, not only after breast augmentation with silicone implants, but also as a very rare vaccination side effect, such as Gulf war syndrome or macrophagic myofasciitis syndrome. Diseases whose symptoms developed after such adjuvant exposure are called autoimmune/ inlammatory syndrome induced by adjuvants (ASIA). The group of adjuvants includes not only silicone implants, silica, squalen and aluminium, but also ink components used for making tattoos. Analyzing the available reports on the inluence of adjuvants on the development of autoimmune diseases, the conclusion is that apart from long -term silicone exposure, the coexistence of other factors such as genetic or environmental is also necessary. Metaanalyses clearly do not conirm an increased risk of developing autoimmune disease after breast augmentation with silicone implants, or tattooing, but it seems that among these patients there is a group that is more predestined to develop disease symptoms. In the general population the beneits of vaccination are obvious, and the risk of severe adverse events following immunisation is incomparably lower than the risk of developing a speciic disease and its complications, also for patients with diagnosed autoimmune diseases. Because of data heterogeneity in previous studies and dificulties in diagnosing ASIA it seems necessary to conduct further analyses of adjuvants’ inluence on autoimmune disease development, and to reine ASIA diagnostic criteria, which now allow too easy a diagnosis of this syndrome.

Association of fecal calprotectin concentrations with disease severity, response to treatment, and other biomarkers in dogs with chronic inflammatory enteropathies

PubMed Central

Berghoff, Nora; Mansell, Joanne; Grützner, Niels; Parnell, Nolie K.; Gurtner, Corinne; Suchodolski, Jan S.; Steiner, Jörg M.

2018-01-01

Background Calprotectin is a marker of inflammation, but its clinical utility in dogs with chronic inflammatory enteropathies (CIE) is unknown. Objective Evaluation of fecal calprotectin in dogs with biopsy‐confirmed CIE. Animals 127 dogs. Methods Prospective case‐control study. Dogs were assigned a canine chronic enteropathy clinical activity index (CCECAI) score, and histologic lesions severity was assessed. Fecal calprotectin, fecal S100A12, and serum C‐reactive protein (CRP) were measured. Food‐ or antibiotic‐responsive cases (FRE/ARE, n = 13) were distinguished from steroid‐/immunosuppressant‐responsive or ‐refractory cases (SRE/IRE, n = 20). Clinical response to treatment in SRE/IRE dogs was classified as complete remission (CR), partial response (PR), or no response (NR). Results Fecal calprotectin correlated with CCECAI (ρ = 0.27, P = .0065) and fecal S100A12 (ρ = 0.90, P < .0001), some inflammatory criteria, and cumulative inflammation scores, but not serum CRP (ρ = 0.16, P = .12). Dogs with SRE/IRE had higher fecal calprotectin concentrations (median: 2.0 μg/g) than FRE/ARE dogs (median: 1.4 μg/g), and within the SRE/IRE group, dogs with PR/NR had higher fecal calprotectin (median: 37.0 μg/g) than dogs with CR (median: 1.6 μg/g). However, both differences did not reach statistical significance (both P = .10). A fecal calprotectin ≥15.2 μg/g separated both groups with 80% sensitivity (95% confidence interval [95%CI]: 28%‐100%) and 75% specificity (95%CI: 43%‐95%). Conclusions and Clinical Importance Fecal calprotectin could be a useful surrogate marker of disease severity in dogs with CIE, but larger longitudinal studies are needed to evaluate its utility in predicting the response to treatment. PMID:29460444

Use of a Granulocyte Immunofluorescence Assay Designed for Humans for Detection of Antineutrophil Cytoplasmic Antibodies in Dogs with Chronic Enteropathies.

PubMed

Florey, J; Viall, A; Streu, S; DiMuro, V; Riddle, A; Kirk, J; Perazzotti, L; Affeldt, K; Wagner, R; Vaden, S; Harris, T; Allenspach, K

2017-07-01

Perinuclear antineutrophil cytoplasmic antibodies (pANCA) previously have been shown to be serum markers in dogs with chronic enteropathies, with dogs that have food-responsive disease (FRD) having higher frequencies of seropositivity than dogs with steroid-responsive disease (SRD). The indirect immunofluorescence (IIF) assay used in previous publications is time-consuming to perform, with low interobserver agreement. We hypothesized that a commercially available granulocyte IIF assay designed for humans could be used to detect perinuclear antineutrophil cytoplasmic antibodies in dogs. Forty-four dogs with FRD, 20 dogs with SRD, 20 control dogs, and 38 soft-coated wheaten terrier (SCWT) or SCWT-cross dogs. A granulocyte assay designed for humans was used to detect pANCA, cANCA, and antinuclear antibodies (ANA), as well as antibodies against proteinase-3 protein (PR-3) and myeloperoxidase protein (MPO) in archived serum samples. Sensitivity of the granulocyte assay to predict FRD in dogs was 0.61 (95% confidence interval (CI), 0.45, 0.75), and specificity was 1.00 (95% CI, 0.91, 1.00). A significant association was identified between positive pANCA or cANCA result and diagnosis of FRD (P < 0.0001). Agreement between the two assays to detect ANCA in the same serum samples from SCWT with protein-losing enteropathy/protein-losing nephropathy (PLE/PLN) was substantial (kappa, 0.77; 95% CI, 0.53, 1.00). Eight ANCA-positive cases were positive for MPO or PR-3 antibodies. The granulocyte immunofluorescence assay used in our pilot study was easy and quick to perform. Agreement with the previously published method was good. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Airway Autoimmune Inflammatory Response (AAIR) Syndrome: An Asthma-Autoimmune Overlap Disorder?

PubMed

Spencer, Chantal Y; Millman, Jennifer; Veiga, Keila; Vicencio, Alfin G

2018-02-15

Asthma encompasses numerous phenotypes that may require alternate approaches to diagnosis and therapy, particularly for patients whose symptoms remain poorly controlled despite escalating treatment. We describe 3 patients with apparent asthma who demonstrated unusual findings on cryobiopsy by flexible bronchoscopy and responded to therapy directed against autoimmune disease. Copyright © 2018 by the American Academy of Pediatrics.

Peptides Against Autoimmune Neurodegeneration.

PubMed

Stepanov, Alexey; Lomakin, Yakov; Gabibov, Alexander; Belogurov, Alexey

2017-01-01

The mammalian immune system is a nearly perfect defensive system polished by a hundred million years of evolution. Unique flexibility and adaptivity have created a virtually impenetrable barrier to numerous exogenous pathogens that are assaulting us every moment. Unfortunately, triggers that remain mostly enigmatic will sometimes persuade the immune system to retarget against self-antigens. This civil war remains underway, showing no mercy and taking no captives, eventually leading to irreversible pathological changes in the human body. Research that has emerged during the last two decades has given us hope that we may have a chance to overcome autoimmune diseases using a variety of techniques to "reset" the immune system. In this report, we summarize recent advances in utilizing short polypeptides - mostly fragments of autoantigens - in the treatment of autoimmune neurodegeneration. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Association of sarcopenia with both latent autoimmune diabetes in adults and type 2 diabetes: a cross-sectional study.

PubMed

Bouchi, Ryotaro; Fukuda, Tatsuya; Takeuchi, Takato; Nakano, Yujiro; Murakami, Masanori; Minami, Isao; Izumiyama, Hajime; Hashimoto, Koshi; Yoshimoto, Takanobu; Ogawa, Yoshihiro

2017-06-01

To investigate the association of both latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2DM) with muscle mass and function (sarcopenia). Japanese patients with LADA (N=20), T2DM (N=208), and control subjects (N=41) were included in this cross-sectional study. The definition of LADA was based on age of onset (≥30), positive glutamic acid decarboxylase autoantibodies, and insulin requirement within the first 6months after diagnosis. Sarcopenia was diagnosed by the criteria for Asians, using skeletal muscle index (male <7.0 and female <5.4) and grip strength (male <26.0kg and female <18.0kg). The odds ratio (OR) with a 95% confidence interval (CI) was estimated using logistic regression. The prevalence of sarcopenia was higher in LADA (35.0%) than in either T2DM (13.3%) or control subjects (9.8%). LADA was significantly associated with an increased risk for sarcopenia in a multivariate model in which age and body mass index were incorporated (OR: 9.57, 95% CI: 1.86-49.27). In contrast, T2DM tended to be associated with an increased risk for sarcopenia (OR: 2.99, 95% CI: 0.83-10.80). This study provides evidence that patients with LADA are at a high risk for sarcopenia compared to those with T2DM or to control subjects. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Immunoglobulin E-Mediated Autoimmunity

PubMed Central

Maurer, Marcus; Altrichter, Sabine; Schmetzer, Oliver; Scheffel, Jörg; Church, Martin K.; Metz, Martin

2018-01-01

The study of autoimmunity mediated by immunoglobulin E (IgE) autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP), and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them. PMID:29686678

Clinical heterogeneity in autoimmune acute liver failure

PubMed Central

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

2007-01-01

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

Is There an Association Between Heparin-Induced Thrombocytopenia (HIT) and Autoimmune Disease?

PubMed

Klinkhammer, Brent; Gruchalla, Michael

2018-03-01

Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin G medicated autoimmune disorder associated with several negative clinical outcomes including increased morbidity, mortality, and increased medical costs. Previous studies have shown associations between comorbid autoimmune diseases, but there is little known about associations between HIT and autoimmunity. To provide clinical data to suggest an association between HIT and autoimmunity. Retrospective chart review of 59 cases with a diagnosis of HIT and 251 matched controls without a HIT diagnosis, comparing the prevalence of autoimmunity in each group. A single, large upper Midwest health care system. Patients with a diagnosis of HIT were significantly more likely to have a comorbid autoimmune disease than those without a HIT diagnosis (55.9% vs 10.8%, P < 0.001). In disease-specific analyses, patients with a diagnosis of HIT were significantly more likely to have a diagnosis of antiphospholipid syndrome (15.3% vs 0.0%, P < 0.001), systemic lupus erythematous (8.5% vs 0.4%, P = 0.001), rheumatoid arthritis (5.1% vs 0.0%, P = 0.007), Hashimoto's thyroiditis (13.6% vs 3.6%, P = 0.006), or nonischemic cardiomyopathy (5.1% vs 0.0%, P = 0.007). Patients diagnosed with HIT were significantly older than controls ( P < 0.001). This novel study gives evidence to suggest an association between HIT and autoimmune disease and suggests a need for more research into the relationship between HIT and autoimmunity. These results could alter the anticoagulation management of venous thromboembolism and acute coronary syndrome in patients with a previously identified autoimmune disease. Copyright© Wisconsin Medical Society.

My self as an other: on autoimmunity and "other" paradoxes.

PubMed

Cohen, E

2004-06-01

The rubric autoimmunity currently encompasses sixty to seventy diverse illnesses which affect many of the tissues of the human body. Western medical practice asserts that the crisis known as autoimmune disease arises when a biological organism compromises its own integrity by misrecognising parts of itself as other than itself and then seeks to eliminate these unrecognised and hence antagonistic aspects of itself. That is, autoimmune illnesses seem to manifest the contradictory and sometimes deadly proposition that the "identity": body/self both is and is not "itself". Based on the assumption that under normal circumstances "the self" ought to coincide naturally with "the body"-or at the very least the self ought to inhabit the living location of the body more or less unproblematically-this scientific paradigm depicts autoimmune illness as a vital paradox. Yet for those of us who have lived through the experience of an autoimmune crisis, the living paradox that we embody may also lead us to question the basis upon which these medical assumptions rest. This essay raises some of these questions.

Autoimmune lymphoproliferative syndrome: more than a FAScinating disease

PubMed Central

Bride, Karen; Teachey, David

2017-01-01

Autoimmune lymphoproliferative syndrome (ALPS) is an inherited syndrome characterized by abnormal lymphocyte survival caused by failure of apoptotic mechanisms to maintain lymphocyte homeostasis. This failure leads to the clinical manifestations of non-infectious and non-malignant lymphadenopathy, splenomegaly, and autoimmune pathology, most commonly, autoimmune cytopenias. Since ALPS was first characterized in the early 1990s, insights in disease biology have improved both diagnosis and management of this syndrome. Sirolimus is the best-studied and most effective corticosteroid-sparing therapy for ALPS and should be considered first-line for patients in need of chronic treatment. This review highlights practical clinical considerations for the diagnosis and management of ALPS. Further studies could reveal new proteins and regulatory pathways that are critical for lymphocyte activation and apoptosis. PMID:29123652

Autoimmune Progesterone Dermatitis Presenting as Stevens-Johnson Syndrome.

PubMed

Drayer, Sara M; Laufer, Larry R; Farrell, Maureen E

2017-10-01

Autoimmune progesterone dermatitis is an uncommon disease presenting with cyclical skin eruptions corresponding with the menstrual cycle luteal phase. Because symptoms are precipitated by rising progesterone levels, treatment relies on hormone suppression. A 22-year-old nulligravid woman presented with symptoms mistaken for Stevens-Johnson syndrome. A cyclic recurrence of her symptoms was noted, and the diagnosis of autoimmune progesterone dermatitis was made by an intradermal progesterone challenge. After 48 months, she remained refractory to medical management and definitive surgical treatment with bilateral oophorectomy was performed. Autoimmune progesterone dermatitis is a challenging diagnosis owing to its rarity and variety of clinical presentations. Treatment centers on suppression of endogenous progesterone and avoidance of exogenous triggers. When these modalities fail, surgical management must be undertaken.

Upregulation of toll-like receptors in chronic enteropathies in dogs.

PubMed

Burgener, I A; König, A; Allenspach, K; Sauter, S N; Boisclair, J; Doherr, M G; Jungi, T W

2008-01-01

Inflammatory bowel disease (IBD) is thought to result from a dysregulated interaction between the host immune system and commensal microflora. Toll-like receptors (TLRs) recognize microbe-associated molecular patterns (MAMPs), but their role in enteropathies in dogs is unknown. That there is a dysregulation of TLRs recognizing bacterial MAMPs in dogs with IBD. Sixteen healthy beagles and 12 dogs with steroid-treated (ST) and 23 dogs with food-responsive (FR) diarrhea. Prospective, observational study. mRNA expression of canine TLR2, 4, and 9 was evaluated by quantitative real-time RT-PCR in duodenal and colonic biopsies obtained before and after standard therapy. Samples from control dogs were taken at necropsy, with additional biopsies of stomach, jejunum, ileum, and mesenteric lymph node in 6 dogs. There were significant differences (P< or = .017) in expression of TLR2, 4, and 9 between the 6 sampled locations in healthy control dogs (lymph node > small intestine > or = colon). Before therapy, ST expressed more mRNA than control dogs for all 3 receptors (P < .05). There were no significant differences between pretreatment and posttreatment values, even though 32/35 dogs improved clinically. No associations were found when comparing receptor mRNA expression with either histology or clinical activity scores. Bacteria-responsive TLR2, 4, and 9 are upregulated in duodenal and colonic mucosa in IBD. This might lead to increased inflammation through interaction with the commensal flora. The absence of significant changes after therapy despite clinical improvement might point toward the existence of a genetic predisposition to IBD as described in human IBD.

Breaking Tolerance to Thyroid Antigens: Changing Concepts in Thyroid Autoimmunity

PubMed Central

Rapoport, Basil

2014-01-01

Thyroid autoimmunity involves loss of tolerance to thyroid proteins in genetically susceptible individuals in association with environmental factors. In central tolerance, intrathymic autoantigen presentation deletes immature T cells with high affinity for autoantigen-derived peptides. Regulatory T cells provide an alternative mechanism to silence autoimmune T cells in the periphery. The TSH receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (Tg) have unusual properties (“immunogenicity”) that contribute to breaking tolerance, including size, abundance, membrane association, glycosylation, and polymorphisms. Insight into loss of tolerance to thyroid proteins comes from spontaneous and induced animal models: 1) intrathymic expression controls self-tolerance to the TSHR, not TPO or Tg; 2) regulatory T cells are not involved in TSHR self-tolerance and instead control the balance between Graves' disease and thyroiditis; 3) breaking TSHR tolerance involves contributions from major histocompatibility complex molecules (humans and induced mouse models), TSHR polymorphism(s) (humans), and alternative splicing (mice); 4) loss of tolerance to Tg before TPO indicates that greater Tg immunogenicity vs TPO dominates central tolerance expectations; 5) tolerance is induced by thyroid autoantigen administration before autoimmunity is established; 6) interferon-α therapy for hepatitis C infection enhances thyroid autoimmunity in patients with intact immunity; Graves' disease developing after T-cell depletion reflects reconstitution autoimmunity; and 7) most environmental factors (including excess iodine) “reveal,” but do not induce, thyroid autoimmunity. Micro-organisms likely exert their effects via bystander stimulation. Finally, no single mechanism explains the loss of tolerance to thyroid proteins. The goal of inducing self-tolerance to prevent autoimmune thyroid disease will require accurate prediction of at-risk individuals together with an antigen

N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Gangduo; Wang, Jianling; Ma, Huaxian

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL +/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water). TCEmore » exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies. - Highlights: • TCE led to increased autoantibodies, supporting its potential to induce autoimmunity. • TCE exposure led to increases in lipid perioxidation and protein carbonyls. • TCE exposure

Thyroid Autoantibodies Are Rare in Nonhuman Great Apes and Hypothyroidism Cannot Be Attributed to Thyroid Autoimmunity

PubMed Central

Aliesky, Holly; Courtney, Cynthia L.; Rapoport, Basil

2013-01-01

The great apes include, in addition to Homo, the genera Pongo (orangutans), Gorilla (gorillas), and Pan, the latter comprising two species, P. troglodytes (chimpanzees) and P. paniscus (bonobos). Adult-onset hypothyroidism was previously reported in 4 individual nonhuman great apes. However, there is scarce information on normal serum thyroid hormone levels and virtually no data for thyroid autoantibodies in these animals. Therefore, we examined thyroid hormone levels and TSH in all nonhuman great ape genera including adults, adolescents, and infants. Because hypothyroidism in humans is commonly the end result of thyroid autoimmunity, we also tested healthy and hypothyroid nonhuman great apes for antibodies to thyroglobulin (Tg), thyroid peroxidase (TPO), and the TSH receptor (TSHR). We established a thyroid hormone and TSH database in orangutans, gorillas, chimpanzees, and bonobos (447 individuals). The most striking differences are the greatly reduced free-T4 and free-T3 levels in orangutans and gorillas vs chimpanzees and bonobos, and conversely, elevated TSH levels in gorillas vs Pan species. Antibodies to Tg and TPO were detected in only 2.6% of adult animals vs approximately 10% in humans. No animals with Tg, TPO, or TSHR antibodies exhibited thyroid dysfunction. Conversely, hypothyroid nonhuman great apes lacked thyroid autoantibodies. Moreover, thyroid histology in necropsy tissues was similar in euthyroid and hypothyroid individuals, and lymphocytic infiltration was absent in 2 hypothyroid animals. In conclusion, free T4 and free T3 are lower in orangutans and gorillas vs chimpanzees and bonobos, the closest living human relatives. Moreover, thyroid autoantibodies are rare and hypothyroidism is unrelated to thyroid autoimmunity in nonhuman great apes. PMID:24092641

Cellular stress and innate inflammation in organ-specific autoimmunity: lessons learned from vitiligo

PubMed Central

Harris, John E.

2015-01-01

Summary For decades, research in autoimmunity has focused primarily on immune contributions to disease. Yet recent studies report elevated levels of reactive oxygen species (ROS) and abnormal activation of the unfolded protein response (UPR) in cells targeted by autoimmunity, implicating cellular stress originating from the target tissue as a contributing factor. A better understanding of this contribution may help to answer important lingering questions in organ-specific autoimmunity, like what factors initiate disease, and what directs its tissue specificity. Vitiligo, an autoimmune disease of the skin, has been the focus of translational research for over 30 years, and both melanocyte stress and immune mechanisms have been thought to be mutually exclusive explanations for pathogenesis. Chemical-induced vitiligo is a unique clinical presentation that reflects the importance of environmental influences on autoimmunity, provides insight into a new paradigm linking cell stress to the immune response, and serves as a template for other autoimmune diseases. In this review I will discuss the evidence for cell stress contributions to a number of autoimmune diseases, the questions that remain, and how vitiligo, an underappreciated example of organ-specific autoimmunity, helps to answer them. PMID:26683142

The present and the future in the diagnosis and management of celiac disease

PubMed Central

Castillo, Natalia E.; Theethira, Thimmaiah G.; Leffler, Daniel A.

2015-01-01

Celiac disease is an autoimmune enteropathy caused by gluten in genetically predisposed individuals. In celiac disease, adaptive and innate immune activation results in intestinal damage and a wide range of clinical manifestations. In the past, celiac disease was thought to result in signs and symptoms solely related to the gastrointestinal tract. Now, more than half of the adult population presents with extra-intestinal manifestations that can also be expected to improve on a gluten-free diet. For this reason, it is recommended that physicians have a low threshold of suspicion for celiac disease. Current knowledge of the immune pathogenesis of this autoimmune disease has served as a catalyst for the development of novel diagnostic tools and therapeutics. Over the years, highly sensitive and specific serological assays, in addition to genetic markers, have been found to target specific steps in the cascade pathway of celiac disease. Also the advent of the gluten challenge has enabled experts to design diagnostic algorithms and monitor clinical responses in clinical trials. The gluten challenge has provided substantial benefit in the advance of novel therapeutics as an adjuvant treatment to the gluten free diet. Generally, a strict gluten-free diet is highly burdensome to patients and can be limited in its efficacy. Alternative therapies—including gluten modification, modulation of intestinal permeability and immune response—could be central to the future treatment of celiac disease. PMID:25326000

Is selenium supplementation in autoimmune thyroid diseases justified?

PubMed

Winther, Kristian H; Bonnema, Steen J; Hegedüs, Laszlo

2017-10-01

This review provides an appraisal of recent evidence for or against selenium supplementation in patients with autoimmune thyroid diseases, and discusses possible effect mechanisms. Epidemiological data suggest an increased prevalence of autoimmune thyroid diseases under conditions of low dietary selenium intake. Two systematic reviews have evaluated controlled trials among patients with autoimmune thyroiditis and report that selenium supplementation decreases circulating thyroid autoantibodies. The immunomodulatory effects of selenium might involve reducing proinflammatory cytokine release. However, clinically relevant effects of selenium supplementation, including improvement in quality of life, are more elusive. In Graves' disease, some, but not all, trials indicate that adjuvant selenium supplementation enhances the restoration of biochemical euthyroidism, and might benefit patients with mild Graves' orbitopathy. The use of selenium supplementation as adjuvant therapy to standard thyroid medication may be widespread, but a growing body of evidence yields equivocal results. The available evidence from trials does not support routine selenium supplementation in the standard treatment of patients with autoimmune thyroiditis or Graves' disease. However, correction of moderate to severe selenium deficiency may offer benefits in preventing, as well as treating, these disorders. Molecular mechanisms have been proposed, but further studies are needed.

Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases

PubMed Central

Opazo, Maria C.; Ortega-Rocha, Elizabeth M.; Coronado-Arrázola, Irenice; Bonifaz, Laura C.; Boudin, Helene; Neunlist, Michel; Bueno, Susan M.; Kalergis, Alexis M.; Riedel, Claudia A.

2018-01-01

The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases. PMID:29593681

Role of inflammasomes in inflammatory autoimmune rheumatic diseases.

PubMed

Yi, Young-Su

2018-01-01

Inflammasomes are intracellular multiprotein complexes that coordinate anti-pathogenic host defense during inflammatory responses in myeloid cells, especially macrophages. Inflammasome activation leads to activation of caspase-1, resulting in the induction of pyroptosis and the secretion of pro-inflammatory cytokines including interleukin (IL)-1β and IL-18. Although the inflammatory response is an innate host defense mechanism, chronic inflammation is the main cause of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and Sjögren's syndrome (SS). Since rheumatic diseases are inflammatory/autoimmune disorders, it is reasonable to hypothesize that inflammasomes activated during the inflammatory response play a pivotal role in development and progression of these diseases. Indeed, previous studies have provided important observations that inflammasomes are actively involved in the pathogenesis of inflammatory/autoimmune rheumatic diseases. In this review, we summarize the current knowledge on several types of inflammasomes during macrophage-mediated inflammatory responses and discuss recent research regarding the role of inflammasomes in the pathogenesis of inflammatory/autoimmune rheumatic diseases. This avenue of research could provide new insights for the development of promising therapeutics to treat inflammatory/autoimmune rheumatic diseases.

Childhood Weight Gain and Thyroid Autoimmunity at Age 60–64 Years: The 1946 British Birth Cohort Study

PubMed Central

Kuh, Diana; Pierce, Mary; Franklyn, Jayne A.

2013-01-01

Background: Complex bidirectional relationships have been described between body weight, thyroid function, and risk of thyroid disorders, including thyroid autoimmunity. We used a life-course approach to examine the potential association of childhood or adult body weight with the risk of thyroid autoimmunity and other thyroid disorders at age 60–64 years in a large population-based birth cohort study. Methods: In the UK Medical Research Council 1946 British Birth Cohort study, at age 60–64 years, 1277 women and 1185 men (78% of the target sample) responded to a postal questionnaire, which included questions on thyroid disease and thyroid medication. Circulating antithyroid peroxidase antibodies, free T4, and TSH concentrations were measured in 1057 women and 997 men at a subsequent clinic visit. Birth weight was recorded, and height and weight were measured at ages 2, 4, 6, 7, 11, 15 years and also repeatedly in adulthood. Results: At age 60–64 years, 10.9% of women (139 of 1277) and 2.3% of men (27 of 1185) reported they were taking T4, and 11.5% of women (122 of 1057) and 3.3% of men (33 of 997) had positive anti-TPO antibodies (>100 IU/mL), consistent with thyroid autoimmunity. Among women, both T4 use and positive anti-TPO antibodies at age 60–64 years were positively associated with childhood body weight, childhood overweight, and adult body mass index. Childhood weight gain between 0 and 14 years of age was positively associated with later T4 use (odds ratio 1.21, 95% confidence interval 1.03–1.42) and positive anti-TPO antibodies (1.21, 1.00–1.47). Women who were overweight or obese at age 14 years (127 of 972) had a higher risk of later positive anti-TPO antibodies (2.05, 1.12–3.76). In men and women without any thyroid disorders, serum free T4 concentrations were inversely associated with concurrent body mass index (P = .002). Conclusions: Childhood weight gain and childhood overweight conferred an increased susceptibility to later

Resolution of Autoimmune Oophoritis after Thymectomy in a Myasthenia Gravis Patient

PubMed Central

Özdemir, Özlem; Eren, Erdal; Sağlam, Halil; Okan, Mehmet; Tarım, Ömer Faruk

2011-01-01

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

Steroids and Autoimmunity.

PubMed

Trombetta, Amelia Chiara; Meroni, Marianna; Cutolo, Maurizio

2017-01-01

From the middle of the 19th century, it is known that endocrine and immune systems interact bi-directionally in different processes that ensure organism homeostasis. Endocrine and nervous systems have a pivotal role in the balancing of pro- and anti-inflammatory functions of immune system, and constitute a complex circadian neuroendocrine network. Autoimmune diseases have in fact a complex pathogenic origin in which the importance of endocrine system was demonstrated. In this chapter, we will mention the structure and function of steroidal hormones involved in the neuroendocrine immune network and we will address the ways in which endocrine and immune systems influence each other, in a bi-directional fashion. Adrenal hormones, sex hormones, vitamin D, and melatonin and prolactin importantly all contribute to the homeostasis of the immune system. Indeed, some of the steroidal hormone activities determine inhibition or stimulation of immune system components, in both physiological (i.e. suppression of an unwanted response in pregnancy, or stimulation of a protective response in infections) and pathological conditions. We will finally mention the rationale for optimization of exogenous administration of glucocorticoids in chronic autoimmune diseases, and the latest developments concerning these drugs. © 2017 S. Karger AG, Basel.

[Seric 21-hydroxilase antibodies in patients with anti-microsomal fraction antibodies. Autoimmune polyendocrine syndrome].

PubMed

Botta, Silvia; Roveto, Silvana; Rimoldi, Daniel

2007-01-01

Autoimmune polyendocrine syndrome (APS) is the association of autoimmune endocrine diseases, with other autoimmune nonendocrine disorders. APS types 1, 2 and 4 include autoimmune adrenalitis; this suggests the presence of autoantibodies. A specific serological marker for these is the anti 21- hydroxilase autoantibody (a21-OH). APS type 2 is the association of autoimmune adrenalitis, to autoimmune thyroid disease and/or diabetes mellitus, all these are induced by autoantibodies. Alopecia, vitiligo, myasthenia and other manifestations can be minor components. We sought to establish the prevalence of seric a21-OH in patients with positive anti-microsomal fraction autoantibodies, autoimmune thyroid disease and/or non-endocrine autoimmune diseases. We also aimed to diagnose incomplete forms of APS and to follow up patients at risk of progression to complete forms of APS. A population of 72 patients and another of 60 controls with negative anti-microsomal fraction autoantibodies were studied. Elevated seric a21-OH were found in two patients. Patient A with 47 U/ml had autoimmune hypothyroidism and myasthenia; and patient B with 8.75 U/ml had autoimmune hypothyrodism and vitiligo; they both lacked adrenal insufficiency. Seric a21-OH had a prevalence of 2.8%. Regarding the adrenal component, patients A and B had an incomplete and latent APS type 2. Considering a21-OH as markers of latent endocrine autoimmune diseases and taking into account the eventual risk of developing clinical manifestations, periodic biochemical and clinical follow-ups are recommended.

HYPERAUTOFLUORESCENT RING IN AUTOIMMUNE RETINOPATHY

PubMed Central

LIMA, LUIZ H.; GREENBERG, JONATHAN P.; GREENSTEIN, VIVIENNE C.; SMITH, R. THEODORE; SALLUM, JULIANA M. F.; THIRKILL, CHARLES; YANNUZZI, LAWRENCE A.; TSANG, STEPHEN H.

2015-01-01

Purpose To report the presence of a hyperautofluorescent ring and corresponding spectral-domain optical coherence tomography (SD-OCT) features seen in patients with autoimmune retinopathy. Methods All eyes were evaluated by funduscopic examination, full-fleld electroretinography, fundus autofluorescence, and SD-OCT. Further confirmation of the diagnosis was obtained with immunoblot and immunohistochemistry testing of the patient’s serum. Humphrey visual fields and microperimetry were also performed. Results Funduscopic examination showed atrophic retinal pigment epithelium (RPE) associated with retinal artery narrowing but without pigment deposits. The scotopic and photopic full-field electroretinograms were nondetectable in three patients and showed a cone–rod pattern of dysfunction in one patient. Fundus autofluorescence revealed a hyperautofluorescent ring in the parafoveal region, and the corresponding SD-OCT demonstrated loss of the photoreceptor inner segment–outer segment junction with thinning of the outer nuclear layer from the region of the hyperautofluorescent ring toward the retinal periphery. The retinal layers were generally intact within the hyperautofluorescent ring, although the inner segment–outer segment junction was disrupted, and the outer nuclear layer and photoreceptor outer segment layer were thinned. Conclusion This case series revealed the structure of the hyperautofluorescent ring in autoimmune retinopathy using SD-OCT. Fundus autofluorescence and SD-OCT may aid in the diagnosis of autoimmune retinopathy and may serve as a tool to monitor its progression. PMID:22218149

Capsaicin-enriched diet ameliorates autoimmune neuritis in rats.

PubMed

Motte, Jeremias; Ambrosius, Björn; Grüter, Thomas; Bachir, Hussein; Sgodzai, Melissa; Pedreiturria, Xiomara; Pitarokoili, Kalliopi; Gold, Ralf

2018-04-24

Autoimmune neuropathies are common PNS disorders and effective treatment is challenging. Environmental influence and dietary components are known to affect the course of autoimmune diseases. Capsaicin as pungent component of chili-peppers is common in human nutrition. An influence of capsaicin on autoimmune diseases has been postulated. We tested capsaicin in the animal model of experimental autoimmune neuritis (EAN) in Lewis rat. Rats were immunized with P2-peptide and were treated with capsaicin in different preventive settings. Electrophysiological, histological, and molecular biological analyses of the sciatic nerve were performed to analyze T-cell and macrophage cell count, TRPV1, and cytokine expression. Moreover, FACS analyses including the intestinal immune system were executed. We observed an immunomodulatory effect of an early preventive diet-concept, where a physiological dosage of oral capsaicin was given 10 days before immunization in EAN. A reduced inflammation of the sciatic nerve was significant detectable clinically, electrophysiologically (CMAPs reduced in control group p < 0.01; increase of nerve conduction blocks in control group p < 0.05), histologically (significant reduction of T-cells, macrophages and demyelination), and at cytokine level. In contrast, this therapeutic effect was missing with capsaicin given from the day of immunization onwards. As possible underlying mechanism, we were able to show changes in the expression of the capsaicin receptor in the sciatic nerve and the small intestine, as well as altered immune cell populations in the small intestine. This is the first report about the immunomodulatory effect of the common nutrient, capsaicin, in an experimental model for autoimmune neuropathies.

Asbestos-induced autoimmunity in C57BL/6 mice.

PubMed

Pfau, Jean C; Sentissi, Jami J; Li, Sheng'ai; Calderon-Garciduenas, Lilian; Brown, Jared M; Blake, David J

2008-04-01

Environmental impacts on autoimmunity have significant public health implications. Epidemiological studies have shown associations between exposure to airborne silicates, such as crystalline silica or asbestos, and autoimmunity, but the etiology remains unclear. The purpose of this study was to test the hypothesis that asbestos could lead to a specific pattern of autoantibodies and pathology indicative of systemic autoimmune disease (SAID). Female C57Bl/6 mice were instilled intratracheally with 2 doses x 60 microg/mouse of amphibole asbestos (tremolite), wollastonite (a non-fibrogenic control fiber), or saline alone. Serum samples were collected and urine was checked for protein bi-weekly for 7 months. By 26 weeks, the asbestos-instilled animals had a significantly higher frequency of positive anti-nuclear antibody (ANA) tests compared to wollastonite and saline groups. The majority of positive ANAs showed homogeneous or combined homogeneous/speckled patterns, and tested positive for antibodies to dsDNA and SSA/Ro 52. Serum isotyping showed no significant changes in IgM, IgA, or IgG subclasses. However, there was an overall decrease in the mean IgG serum concentration in asbestos-instilled mice. IgG immune complex deposition was demonstrated in the kidneys of asbestos-instilled mice, with evidence of glomerular and tubule abnormalities suggestive of glomerulonephritis. Flow cytometry demonstrated moderate changes in the percentages of CD25+ T-suppressor cells and B1a B-cells in the superficial cervical lymph nodes of the asbestos-instilled mice. These data demonstrate that asbestos leads to immunologic changes consistent with the development of autoimmunity. This study provides a non-autoimmune prone murine model for use in future elucidation of mechanisms involved in asbestos-induced autoimmune disease.

Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism.

PubMed

Singh, Vijendra K

2009-01-01

Autism causes incapacitating neurologic problems in children that last a lifetime. The author of this article previously hypothesized that autism may be caused by autoimmunity to the brain, possibly triggered by a viral infection. This article is a summary of laboratory findings to date plus new data in support of an autoimmune pathogenesis for autism. Autoimmune markers were analyzed in the sera of autistic and normal children, but the cerebrospinal fluid (CSF) of some autistic children was also analyzed. Laboratory procedures included enzyme-linked immunosorbent assay and protein immunoblotting assay. Autoimmunity was demonstrated by the presence of brain autoantibodies, abnormal viral serology, brain and viral antibodies in CSF, a positive correlation between brain autoantibodies and viral serology, elevated levels of proinflammatory cytokines and acute-phase reactants, and a positive response to immunotherapy. Many autistic children harbored brain myelin basic protein autoantibodies and elevated levels of antibodies to measles virus and measles-mumps-rubella (MMR) vaccine. Measles might be etiologically linked to autism because measles and MMR antibodies (a viral marker) correlated positively to brain autoantibodies (an autoimmune marker)--salient features that characterize autoimmune pathology in autism. Autistic children also showed elevated levels of acute-phase reactants--a marker of systemic inflammation. The scientific evidence is quite credible for our autoimmune hypothesis, leading to the identification of autoimmune autistic disorder (AAD) as a major subset of autism. AAD can be identified by immune tests to determine immune problems before administering immunotherapy. The author has advanced a speculative neuroautoimmune (NAI) model for autism, in which virus-induced autoimmunity is a key player. The latter should be targeted by immunotherapy to help children with autism.

Gulf War Illness as a Brain Autoimmune Disorder

DTIC Science & Technology

2017-10-01

autoimmune disorders, to determine the extent to which GWI reflects autoimmune abnormalities . Altogether, our study will improve knowledge of GWI...University of Minnesota Medical School, Minneapolis, MN 55455, USA d Department of Psychology , University of Minnesota, Minneapolis, MN 55455, USA e...gain further knowledge regarding the nature of GWI brain abnormality . We studied a total of 962 participants from a healthy control population (N

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.

Autoimmune estrogen dermatitis in an infertile female.

PubMed

Elcin, Gonca; Gülseren, Duygu; Bayraktar, Miyase; Gunalp, Serdar; Gurgan, Timur

2017-06-01

Autoimmune estrogen dermatitis is a cyclical cutaneous eruption that occurs premenstrually and goes to the rapid resolution within a few days of menstrual cycles. The disorder has variable clinical manifestations consisting of macules, papules, vesicles, urticarial lesions, bullae, eczematous plaques, and erythema multiforme-like lesions. Herein, we present a case of a 30-year-old woman with attacks of edema and erosions involving the oral and genital mucosal sites on every first day of her menstruation period. She had also multiple endocrinological problems such as hypotroidism and infertility. To determine the sex hormon sensitivity, intradermal skin tests were performed. Based on her personal history and skin test findings, a diagnosis of autoimmune estrogen dermatitis was made. After the oophorectomy, she was free from the skin and mucosal symptoms. We propose that it is important to suspect the diagnosis of autoimmune estrogen dermatitis in patients who present with recurrent cylic eruptions and it must be kept in mind that these patients might have a concomitant infertility.

Humoral Epitope Spreading in Autoimmune Bullous Diseases

PubMed Central

Didona, Dario; Di Zenzo, Giovanni

2018-01-01

Autoimmune blistering diseases are characterized by autoantibodies against structural adhesion proteins of the skin and mucous membranes. Extensive characterization of their autoantibody targets has improved understanding of pathogenesis and laid the basis for the study of antigens/epitopes diversification, a process termed epitope spreading (ES). In this review, we have reported and discussed ES phenomena in autoimmune bullous diseases and underlined their functional role in disease pathogenesis. A functional ES has been proposed: (1) in bullous pemphigoid patients and correlates with the initial phase of the disease, (2) in pemphigus vulgaris patients with mucosal involvement during the clinical transition to a mucocutaneous form, (3) in endemic pemphigus foliaceus, underlining its role in disease pathogenesis, and (4) in numerous cases of disease transition associated with an intermolecular diversification of immune response. All these findings could give useful information to better understand autoimmune disease pathogenesis and to design antigen/epitope specific therapeutic approaches. PMID:29719538

NK cell subsets in autoimmune diseases.

PubMed

Zhang, Cai; Tian, Zhigang

2017-09-01

Natural killer (NK) cells are lymphocytes of the innate immune system. They not only exert cell-mediated cytotoxicity against tumor cells or infected cells, but also play regulatory role through promoting or suppressing functions of other immune cells by secretion of cytokines and chemokines. However, overactivation or dysfunction of NK cells may be associated with pathogenesis of some diseases. NK cells are found to act as a two edged weapon and play opposite roles with both regulatory and inducer activity in autoimmune diseases. Though the precise mechanisms for the opposite effects of NK cells has not been fully elucidated, the importance of NK cells in autoimmune diseases might be associated with different NK cell subsets, different tissue microenvironment and different stages of corresponding diseases. The local tissue microenvironment, unique cellular interactions and different stages of corresponding diseases shape the properties and function of NK cells. In this review, we focus on recent research on the features and function of different NK cell subsets, particularly tissue-resident NK cells in different tissues, and their potential role in autoimmune diseases. Copyright © 2017. Published by Elsevier Ltd.

The Role of Epigenetics in Aging and Autoimmunity

PubMed Central

Grolleau-Julius, Annabelle; Ray, Donna; Yung, Raymond L.

2013-01-01

The decline in immunocompetence with age is accompanied by the increase in the incidence of autoimmune diseases. Aging of the immune system, or immunosenescence, is characterized by a decline of both T and B cell function, and paradoxically the presence of low grade chronic inflammation. There is growing evidence that epigenetics, the study of inherited changes in gene expression that are not encoded by the DNA sequence itself, changes with aging. Interestingly, emerging evidence suggests a key role for epigenetics in human pathologies, including inflammatory and neoplastic disorders. Here we will review the potential mechanisms that contribute to the increase in autoimmune responses in aging. In particular, we will discuss how epigenetic alterations, especially DNA methylation and histone acetylation, are accumulated during aging and how these events contribute to autoimmunity risk. PMID:18432411

The Role of Epigenetics in Aging and Autoimmunity

PubMed Central

Ray, Donna

2009-01-01

The decline in immunocompetence with age is accompanied by the increase in the incidence of autoimmune diseases. Aging of the immune system, or immunosenescence, is characterized by a decline of both T and B cell function, and paradoxically the presence of low-grade chronic inflammation. There is growing evidence that epigenetics, the study of inherited changes in gene expression that are not encoded by the DNA sequence itself, changes with aging. Interestingly, emerging evidence suggests a key role for epigenetics in human pathologies, including inflammatory and neoplastic disorders. Here, we will review the potential mechanisms that contribute to the increase in autoimmune responses in aging. In particular, we will discuss how epigenetic alterations, especially DNA methylation and histone acetylation, are accumulated during aging and how these events contribute to autoimmunity risk. PMID:19653133

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

PubMed Central

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

2014-01-01

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

Understanding mechanisms of autoimmunity through translational research in vitiligo

PubMed Central

Strassner, James P; Harris, John E

2016-01-01

Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells. Once the autoimmune T cell response is established, the IFN-γ-STAT1-CXCL10 signaling axis becomes the primary inflammatory pathway driving both progression and maintenance of vitiligo. This pathway is a tempting target for both existing and developing pharmaceuticals, but further detailing how melanocytes signal their own demise may also lead to new therapeutic targets. Research in vitiligo may be the future key to understand the pathogenesis of organ-specific autoimmunity, as vitiligo is common, reversible, progresses over the life of the individual, has been relatively well-defined, and is quite easy to study using translational and clinical approaches. What is revealed in these studies can lead to innovative treatments and also help elucidate the principles that underlie similar organ-specific autoimmune diseases, especially in cases where the target organ is less accessible. PMID:27764715

The Immunopathogenesis of Chronic Autoimmune Thyroiditis One Century after Hashimoto

PubMed Central

Weetman, Anthony P

2013-01-01

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

Strain-specific induction of experimental autoimmune prostatitis (EAP) in mice.

PubMed

Jackson, Christopher M; Flies, Dallas B; Mosse, Claudio A; Parwani, Anil; Hipkiss, Edward L; Drake, Charles G

2013-05-01

Prostatitis, a clinical syndrome characterized by pelvic pain and inflammation, is common in adult males. Although several induced and spontaneous murine models of prostatitis have been explored, the role of genetic background on induction has not been well-defined. Using a standard methodology for the induction of experimental autoimmune prostatitis (EAP), we investigated both acute and chronic inflammation on several murine genetic backgrounds. In our colony, nonobese diabetic (NOD) mice evinced spontaneous prostatitis that was not augmented by immunization with rat prostate extract (RPE). In contrast, the standard laboratory strain Balb/c developed chronic inflammation in response to RPE immunization. Development of EAP in other strains was variable. These data suggest that Balb/c mice injected with RPE may provide a useful model for chronic prostatic inflammation. Copyright © 2012 Wiley Periodicals, Inc.

Strain-Specific Induction of Experimental Autoimmune Prostatitis (EAP) in Mice

PubMed Central

Jackson, Christopher M.; Flies, Dallas B.; Mosse, Claudio A.; Parwani, Anil; Hipkiss, Edward L.; Drake, Charles G.

2013-01-01

BACKGROUND Prostatitis, a clinical syndrome characterized by pelvic pain and inflammation, is common in adult males. Although several induced and spontaneous murine models of prostatitis have been explored, the role of genetic background on induction has not been well-defined. METHODS Using a standard methodology for the induction of experimental autoimmune prostatitis (EAP), we investigated both acute and chronic inflammation on several murine genetic backgrounds. RESULTS In our colony, nonobese diabetic (NOD) mice evinced spontaneous prostatitis that was not augmented by immunization with rat prostate extract (RPE). In contrast, the standard laboratory strain Balb/c developed chronic inflammation in response to RPE immunization. Development of EAP in other strains was variable. CONCLUSIONS These data suggest that Balb/c mice injected with RPE may provide a useful model for chronic prostatic inflammation. PMID:23129407

Autoimmune hepatitis: a manifestation of immune reconstitution inflammatory syndrome in HIV infected patients?

PubMed

Murunga, Eric; Andersson, Monique; Rensburg, Christo van

2016-07-01

To describe a case series of patients presenting with autoimmune hepatitis after initiation of antiretroviral therapy. The demographics, clinical and laboratory features, and therapeutic response of HIV-infected patients on antiretroviral therapy presenting to our Division between November 2011 and November 2014 with elevated liver enzymes, were analysed. Nine patients with elevated liver enzymes, immunoglobulin G and autoimmune markers in keeping with autoimmune hepatitis were identified. All were anti-hepatitis C virus negative. One patient was hepatitis B surface antigen positive but his hepatitis B viral load was undetectable. All patients denied using any traditional herbal remedies. Liver histology was consistent with autoimmune hepatitis showing interface hepatitis and infiltrates of lymphocytes and plasma cells. Diagnosis was made according to the Autoimmune Hepatitis Group Scoring Systems. All patients were started on 15-20 mg of oral prednisone with clinical and biochemical improvement after 1-6 weeks. Immune reconstitution related autoimmune hepatitis should be considered in the differential diagnosis of hepatitis in the HIV-infected patient on antiretroviral therapy. Liver biopsy should be performed and the diagnosis confirmed using scoring systems developed by the Autoimmune Hepatitis Group. Timely treatment with prednisone and other agents for autoimmune hepatitis is indicated, and can be lifesaving in acute liver failure.

A possible link between the Epstein-Barr virus infection and autoimmune thyroid disorders

PubMed Central

Gwizdek, Katarzyna; Michalski, Marek; Wojnicz, Romuald

2016-01-01

The Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a member of the Herpesviridae virus family. EBV infection can cause infectious mononucleosis (IM) in the lytic phase of EBV’s life cycle. Past EBV infection is associated with lymphomas, and may also result in certain allergic and autoimmune diseases. Although potential mechanisms of autoimmune diseases have not been clearly elucidated, both genetic and environmental factors, such as infectious agents, are considered to be responsible for their development. In addition, EBV modifies the host immune response. The worldwide prevalence of autoimmune diseases shows how common this pathogen is. Normally, the virus stays in the body and remains dormant throughout life. However, this is not always the case, and a serious EBV-related illness may develop later in life. This explains the chronic course of autoimmune diseases that is often accompanied by exacerbations of symptoms. Based on the present studies, EBV infection can cause autoimmune diseases, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), Sjögren’s syndrome, and autoimmune hepatitis. The EBV has also been reported in patients with autoimmune thyroid disorders. Although EBV is not the only agent responsible for the development of autoimmune thyroid diseases, it can be considered a contributory factor. PMID:27833448

A possible link between the Epstein-Barr virus infection and autoimmune thyroid disorders.

PubMed

Dittfeld, Anna; Gwizdek, Katarzyna; Michalski, Marek; Wojnicz, Romuald

2016-01-01

The Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a member of the Herpesviridae virus family. EBV infection can cause infectious mononucleosis (IM) in the lytic phase of EBV's life cycle. Past EBV infection is associated with lymphomas, and may also result in certain allergic and autoimmune diseases. Although potential mechanisms of autoimmune diseases have not been clearly elucidated, both genetic and environmental factors, such as infectious agents, are considered to be responsible for their development. In addition, EBV modifies the host immune response. The worldwide prevalence of autoimmune diseases shows how common this pathogen is. Normally, the virus stays in the body and remains dormant throughout life. However, this is not always the case, and a serious EBV-related illness may develop later in life. This explains the chronic course of autoimmune diseases that is often accompanied by exacerbations of symptoms. Based on the present studies, EBV infection can cause autoimmune diseases, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), Sjögren's syndrome, and autoimmune hepatitis. The EBV has also been reported in patients with autoimmune thyroid disorders. Although EBV is not the only agent responsible for the development of autoimmune thyroid diseases, it can be considered a contributory factor.

B cell–derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity

PubMed Central

Arkatkar, Tanvi

2017-01-01

Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (TFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell–derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed. Here, we report the unexpected finding that a lack of B cell–derived IL-6 abrogates spontaneous GC formation in mouse SLE, resulting in loss of class-switched autoantibodies and protection from systemic autoimmunity. Mechanistically, B cell IL-6 production was enhanced by IFN-γ, consistent with the critical roles for B cell–intrinsic IFN-γ receptor signals in driving autoimmune GC formation. Together, these findings identify a key mechanism whereby B cells drive autoimmunity via local IL-6 production required for TFH differentiation and autoimmune GC formation. PMID:28899868

Toll-Like Receptor Pathways in Autoimmune Diseases.

PubMed

Chen, Ji-Qing; Szodoray, Peter; Zeher, Margit

2016-02-01

Autoimmune diseases are a family of chronic systemic inflammatory disorders, characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen. Several studies suggest that Toll-like receptors (TLRs) play an essential role in the pathogenesis of autoimmune diseases. TLRs belong to the family of pattern recognition receptors (PRRs) that recognize a wide range of pathogen-associated molecular patterns (PAMPs). TLRs are type I transmembrane proteins and located on various cellular membranes. Two main groups have been classified based on their location; the extracelluar group referred to the ones located on the plasma membrane while the intracellular group all located in endosomal compartments responsible for the recognition of nucleic acids. They are released by the host cells and trigger various intracellular pathways which results in the production of proinflammatory cytokines, chemokines, as well as the expression of co-stimulatory molecules to protect against invading microorganisms. In particular, TLR pathway-associated proteins, such as IRAK, TRAF, and SOCS, are often dysregulated in this group of diseases. TLR-associated gene expression profile analysis together with single nucleotide polymorphism (SNP) assessment could be important to explain the pathomechanism driving autoimmune diseases. In this review, we summarize recent findings on TLR pathway regulation in various autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis.

Sex hormones and the genesis of autoimmunity.

PubMed

Ackerman, Lindsay S

2006-03-01

The sexually dimorphic prevalence of autoimmune disease remains one of the most intriguing clinical observations among this group of disorders. While sex hormones have long been recognized for their roles in reproductive functions, within the past 2 decades scientists have found that sex hormones are integral signaling modulators of the mammalian immune system. Sex hormones have definitive roles in lymphocyte maturation, activation, and synthesis of antibodies and cytokines. Sex hormone expression is altered among patients with autoimmune disease, and this variation of expression contributes to immune dysregulation. English-language literature from the last 10 years was reviewed to examine the relationship between sex hormones and the function of the mammalian immune system. Approximately 50 publications were included in this review, and the majority were controlled trials with investigator blinding that compared both male and female diseased and normal subjects. The review provided basic knowledge regarding the broad impact of sex hormones on the immune system and how abnormal sex hormone expression contributes to the development and maintenance of autoimmune phenomena, with a focus on systemic lupus erythematosus, as models of "lupus-prone" mice are readily available. Sex hormones affect the function of the mammalian immune system, and sex hormone expression is different in patients with systemic lupus erythematosus than in healthy subjects. Sex hormones play a role in the genesis of autoimmunity. Future research may provide a therapeutic approach that is capable of altering disease pathogenesis, rather than targeting disease sequelae.

American Autoimmune Related Diseases Association

MedlinePlus

... Policy Contact Us Who We Help Patients ARNet Research Survey AD Knowledge Base Autoimmune Disease List Common Thread ... Planned Giving Shop AARDA Volunteer Take Action ARNet Research Survey Voter Voice Prescription Drug User Fee Act (PDUFA) ...

Impact of pregabalin treatment on synaptic plasticity and glial reactivity during the course of experimental autoimmune encephalomyelitis

PubMed Central

Silva, Gleidy A A; Pradella, Fernando; Moraes, Adriel; Farias, Alessandro; dos Santos, Leonilda M B; de Oliveira, Alexandre L R

2014-01-01

Background Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease that affects young adults. It is characterized by generating a chronic demyelinating autoimmune inflammation in the central nervous system. An experimental model for studying MS is the experimental autoimmune encephalomyelitis (EAE), induced by immunization with antigenic proteins from myelin. Aims The present study investigated the evolution of EAE in pregabalin treated animals up to the remission phase. Methods and results The results demonstrated a delay in the onset of the disease with statistical differences at the 10th and the 16th day after immunization. Additionally, the walking track test (CatWalk) was used to evaluate different parameters related to motor function. Although no difference between groups was obtained for the foot print pressure, the regularity index was improved post treatment, indicating a better motor coordination. The immunohistochemical analysis of putative synapse preservation and glial reactivity revealed that pregabalin treatment improved the overall morphology of the spinal cord. A preservation of circuits was depicted and the glial reaction was downregulated during the course of the disease. qRT-PCR data did not show immunomodulatory effects of pregabalin, indicating that the positive effects were restricted to the CNS environment. Conclusions Overall, the present data indicate that pregabalin is efficient for reducing the seriousness of EAE, delaying its course as well as reducing synaptic loss and astroglial reaction. PMID:25365796

Assessment of Gastric Emptying in Patients with Autoimmune Gastritis.

PubMed

Kalkan, Çağdaş; Soykan, Irfan; Soydal, Çiğdem; Özkan, Elgin; Kalkan, Emra

2016-06-01

Symptoms of patients with autoimmune gastritis are not specific, and some patients may present symptoms suggestive of delayed gastric emptying. This study aims to investigate whether any delay in gastric emptying of solid food exists in patients with autoimmune gastritis and, if so, to identify the factors that might affect delayed gastric emptying. A total of 165 patients (106 women) diagnosed as having autoimmune gastritis were analyzed by means of a gastric emptying test. All patients underwent a standardized scintigraphic gastric emptying study. Patients with delayed gastric emptying and normal gastric emptying tests were then compared by means of factors that might affect gastric emptying. Also 65 patients with functional dyspepsia who had a gastric emptying study constituted the control group. The median gastric emptying T ½ time was 127.43 min (min-max 50-953) for patients with AIG and 81 min (min-max 21-121.6) for functional dyspepsia patients (p < 0.001), and median percent retention at 2 h was 63.8 versus 20.2 (p < 0.001). In multivariate analysis, parameters that affected gastric emptying T ½ time were found as serum gastrin level (OR 1.002, 95 % CI 1.001-1.004, p < 0.001, chronic inflammation (OR 3.689, 95 % CI 1.44-9.39, p < 0.001), and increase in the degree of the atrophy of the gastric mucosa (OR 8.96, 95 % CI 2.98-26.93, p < 0.001). In patients with autoimmune gastritis, gastric emptying is generally delayed. Autoimmune gastritis is an important etiology to explain the finding of delayed gastric emptying on a radionuclide test. This new finding is likely to be relevant to clinicians when evaluating and initiating appropriate medical treatment for patients with autoimmune gastritis manifesting upper gastrointestinal symptoms.

Autoimmune acute liver failure: proposed clinical and histological criteria.

PubMed

Stravitz, R Todd; Lefkowitch, Jay H; Fontana, Robert J; Gershwin, M Eric; Leung, Patrick S C; Sterling, Richard K; Manns, Michael P; Norman, Gary L; Lee, William M

2011-02-01

Identifying autoimmune hepatitis as the etiology of acute liver failure (ALF) is potentially important, because administering corticosteroids might avoid the need for liver transplantation. However, clinical and histological criteria of autoimmune ALF (AI-ALF) have not been defined. Liver sections (biopsies and explants) from a 72-patient subset of the ALF Study Group Registry with indeterminate ALF were reviewed by a pathologist blinded to all clinical data and were diagnosed with probable AI-ALF based on four features suggestive of an autoimmune pathogenesis: distinctive patterns of massive hepatic necrosis (present in 42% of sections), presence of lymphoid follicles (32%), a plasma cell-enriched inflammatory infiltrate (63%), and central perivenulitis (65%). Forty-two sections (58%) were considered probable for AI-ALF; this group demonstrated higher serum globulins (3.7 ± 0.2 g/dL versus 3.0 ± 0.2 g/dL; P = 0.037) and a higher prevalence of antinuclear and/or anti-smooth muscle antibodies (73% versus 48%; P = 0.034) compared to those without histology suggestive of probable AI-ALF. Thirty patients concordant for autoantibodies and probable AI-ALF upon histological analysis were more likely to have the classical autoimmune hepatitis phenotype (female predominance [72% versus 48%; P < 0.05], higher globulins [3.9 ± 0.2 g/dL versus 3.0 ± 0.2 g/dL; P < 0.005], and higher incidence of chronic hepatitis in long-term follow-up [67% versus 17%, P = 0.019]) compared to the population without concordant AI-ALF histology and autoantibodies. Patients with indeterminate ALF often have features of autoimmune disease by histological analysis, serological testing, and clinical recurrence during follow-up. In contrast to classical autoimmune hepatitis, histological features of AI-ALF predominate in the centrilobular zone. Copyright © 2010 American Association for the Study of Liver Diseases.

Mercury and autoimmunity: implications for occupational and environmental health

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silbergeld, Ellen K.; Silva, Ines A.; Nyland, Jennifer F.

Mercury (Hg) has long been recognized as a neurotoxicant; however, recent work in animal models has implicated Hg as an immunotoxicant. In particular, Hg has been shown to induce autoimmune disease in susceptible animals with effects including overproduction of specific autoantibodies and pathophysiologic signs of lupus-like disease. However, these effects are only observed at high doses of Hg that are above the levels to which humans would be exposed through contaminated fish consumption. While there is presently no evidence to suggest that Hg induces frank autoimmune disease in humans, a recent epidemiological study has demonstrated a link between occupational Hgmore » exposure and lupus. In our studies, we have tested the hypothesis that Hg does not cause autoimmune disease directly, but rather that it may interact with triggering events, such as genetic predisposition, exposure to antigens, or infection, to exacerbate disease. Treatment of mice that are not susceptible to Hg-induced autoimmune disease with very low doses and short term exposures of inorganic Hg (20-200 {mu}g/kg) exacerbates disease and accelerates mortality in the graft versus host disease model of chronic lupus in C57Bl/6 x DBA/2 mice. Furthermore, low dose Hg exposure increases the severity and prevalence of experimental autoimmune myocarditis (induced by immunization with cardiac myosin peptide in adjuvant) in A/J mice. To test our hypothesis further, we examined sera from Amazonian populations exposed to Hg through small-scale gold mining, with and without current or past malaria infection. We found significantly increased prevalence of antinuclear and antinucleolar antibodies and a positive interaction between Hg and malaria. These results suggest a new model for Hg immunotoxicity, as a co-factor in autoimmune disease, increasing the risks and severity of clinical disease in the presence of other triggering events, either genetic or acquired.« less

Antibodies against glutamic acid decarboxylase and indices of insulin resistance and insulin secretion in nondiabetic adults: a cross-sectional study

PubMed Central

Mendivil, Carlos O; Toloza, Freddy JK; Ricardo-Silgado, Maria L; Morales-Álvarez, Martha C; Mantilla-Rivas, Jose O; Pinzón-Cortés, Jairo A; Lemus, Hernán N

2017-01-01

Background Autoimmunity against insulin-producing beta cells from pancreatic islets is a common phenomenon in type 1 diabetes and latent autoimmune diabetes in adults. Some reports have also related beta-cell autoimmunity to insulin resistance (IR) in type 2 diabetes. However, the extent to which autoimmunity against components of beta cells is present and relates to IR and insulin secretion in nondiabetic adults is uncertain. Aim To explore the association between antibodies against glutamic acid decarboxylase (GADA), a major antigen from beta cells, and indices of whole-body IR and beta-cell capacity/insulin secretion in adults who do not have diabetes. Methods We studied 81 adults of both sexes aged 30–70, without known diabetes or any autoimmune disease. Participants underwent an oral glucose tolerance test (OGTT) with determination of plasma glucose and insulin at 0, 30, 60, 90, and 120 minutes. From these results we calculated indices of insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] and incremental area under the insulin curve [iAUCins]) and insulin secretion (corrected insulin response at 30 minutes and HOMA beta-cell%). GADAs were measured in fasting plasma using immunoenzymatic methods. Results We found an overall prevalence of GADA positivity of 21.3%, without differences by sex and no correlation with age. GADA titers did not change monotonically across quartiles of any of the IR or insulin secretion indices studies. GADA did not correlate linearly with fasting IR expressed as HOMA-IR (Spearman’s r=−0.18, p=0.10) or postabsorptive IR expressed as iAUCins (r=−0.15, p=0.18), but did show a trend toward a negative correlation with insulin secretory capacity expressed by the HOMA-beta cell% index (r=−0.20, p=0.07). Hemoglobin A1c, body mass index, and waist circumference were not associated with GADA titers. Conclusion GADA positivity is frequent and likely related to impaired beta-cell function among adults

Screening Immunomodulators To Skew the Antigen-Specific Autoimmune Response.

PubMed

Northrup, Laura; Sullivan, Bradley P; Hartwell, Brittany L; Garza, Aaron; Berkland, Cory

2017-01-03

Current therapies to treat autoimmune diseases often result in side effects such as nonspecific immunosuppression. Therapies that can induce antigen-specific immune tolerance provide an opportunity to reverse autoimmunity and mitigate the risks associated with global immunosuppression. In an effort to induce antigen-specific immune tolerance, co-administration of immunomodulators with autoantigens has been investigated in an effort to reprogram autoimmunity. To date, identifying immunomodulators that may skew the antigen-specific immune response has been ad hoc at best. To address this need, we utilized splenocytes obtained from mice with experimental autoimmune encephalomyelitis (EAE) in order to determine if certain immunomodulators may induce markers of immune tolerance following antigen rechallenge. Of the immunomodulatory compounds investigated, only dexamethasone modified the antigen-specific immune response by skewing the cytokine response and decreasing T-cell populations at a concentration corresponding to a relevant in vivo dose. Thus, antigen-educated EAE splenocytes provide an ex vivo screen for investigating compounds capable of skewing the antigen-specific immune response, and this approach could be extrapolated to antigen-educated cells from other diseases or human tissues.

Autoantigens in systemic autoimmunity: critical partner in pathogenesis

PubMed Central

Rosen, A.; Casciola-Rosen, L.

2013-01-01

Understanding the mechanisms of human autoimmune rheumatic diseases presents a major challenge, due to marked complexity involving multiple domains, including genetics, environment and kinetics. In spite of this, the immune response in each of these diseases is largely specific, with distinct autoantibodies associated with different disease phenotypes. Defining the basis of such specificity will provide important insights into disease mechanism. Accumulating data suggest an interesting paradigm for antigen selection in autoimmunity, in which target tissue and immune effector pathways form a mutually reinforcing partnership. In this model, distinct autoantibody patterns in autoimmunity may be viewed as the integrated, amplified output of several interacting systems, including: (i) the specific target tissue, (ii) the immune effector pathways that modify antigen structure and cause tissue damage and dysfunction, and (iii) the homeostatic pathways activated in response to damage (e.g. regeneration/differentiation/cytokine effects). As unique antigen expression and structure may occur exclusively under these amplifying circumstances, it is useful to view the molecules targeted as ‘neo-antigens’, that is, antigens expressed under specific conditions, rather than ubiquitously. This model adds an important new dynamic element to selection of antigen targets in autoimmunity, and suggests that the amplifying loop will only be identified by studying the diseased target tissue in vivo. PMID:19493056

Autoimmune Addison's disease - An update on pathogenesis.

PubMed

Hellesen, Alexander; Bratland, Eirik; Husebye, Eystein S

2018-06-01

Autoimmunity against the adrenal cortex is the leading cause of Addison's disease in industrialized countries, with prevalence estimates ranging from 93-220 per million in Europe. The immune-mediated attack on adrenocortical cells cripples their ability to synthesize vital steroid hormones and necessitates life-long hormone replacement therapy. The autoimmune disease etiology is multifactorial involving variants in immune genes and environmental factors. Recently, we have come to appreciate that the adrenocortical cell itself is an active player in the autoimmune process. Here we summarize the complex interplay between the immune system and the adrenal cortex and highlight unanswered questions and gaps in our current understanding of the disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Targeting B Cells and Plasma Cells in Autoimmune Diseases

PubMed Central

Hofmann, Katharina; Clauder, Ann-Katrin; Manz, Rudolf Armin

2018-01-01

Success with B cell depletion using rituximab has proven the concept that B lineage cells represent a valid target for the treatment of autoimmune diseases, and has promoted the development of other B cell targeting agents. Present data confirm that B cell depletion is beneficial in various autoimmune disorders and also show that it can worsen the disease course in some patients. These findings suggest that B lineage cells not only produce pathogenic autoantibodies, but also significantly contribute to the regulation of inflammation. In this review, we will discuss the multiple pro- and anti-inflammatory roles of B lineage cells play in autoimmune diseases, in the context of recent findings using B lineage targeting therapies. PMID:29740441

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. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Factors associated with elevated serum chromogranin A levels in patients with autoimmune gastritis.

PubMed

Kalkan, Çağdaş; Karakaya, Fatih; Soykan, İrfan

2016-11-01

Chromogranin A is an important tool in the diagnosis of neuroendocrine tumors. Autoimmune gastritis is an autoimmune disorder marked by hypergastrinemia, which stimulates enterochromaffin-like cell proliferation. Chromogranin A is also elevated in autoimmune gastritis patients with a different level of increase in each patient. The goal of this study is to explore constituents that influence serum chromogranin A levels in autoimmune gastritis patients. One hundred and eighty-eight autoimmune gastritis patients and 20 patients with type I gastric carcinoid tumors were analyzed retrospectively and compared to 110 functional dyspepsia patients in terms of factors that might affect serum chromogranin A levels. The mean serum chromogranin A level was 171.17±67.3 ng/mL in autoimmune gastritis patients (n=62) without enterochromaffin-like cell hyperplasia, and 303.3±102.82 ng/mL in patients (n=126) with enterochromaffin-like cell hyperplasia (p<0.001). The presence of corpus atrophy (p=0.026, OR: 5.03, CI 95%: 1.21-20.88, β=1.61) and presence of enterochromaffin-like cell hyperplasia (p=0.017, OR: 6.59, CI 95%: 1.4-31.08, β=1.88) were found as risk factors associated with serum chromogranin A level. Factors influencing raised serum chromogranin A levels in autoimmune gastritis were the presence of ECL cell hyperplasia and serum gastrin levels. Serum chromogranin A levels maybe helpful in distinguishing autoimmune gastritis patients and gastric carcinoid type I from the control group, but not useful in the differentiation of individuals with autoimmune gastritis from patients with gastric carcinoids.

The Pathogenesis of Autoimmune Liver Disease.

PubMed

Arndtz, Katherine; Hirschfield, Gideon M

Autoimmune liver disease (AILD) encompasses 3 main distinct clinical diseases: autoimmune hepatitis, primary biliary cholangitis (formally known as cirrhosis, PBC) and primary sclerosing cholangitis (PSC). These conditions are an important, yet under-appreciated cause of patient morbidity and mortality with ongoing unmet needs for further research and clinical advances. There is observational evidence for genetic predisposition, with all 3 conditions being more common in first degree relatives. AILD is associated with the presence of auto-antibodies and higher risks of other non-hepatic auto-immune conditions. Genetic risk association studies have identified HLA and non-HLA risk loci for the development of disease, with some HLA loci providing prognostic information. This re-enforces the concept that genetic predisposition to autoimmunity is important, likely in the context of environmental exposures. Such environmental triggers are unclear but relevant risks include smoking, drug and xenobiotic exposure as well as the complexities of the microbiome. There is evidence for a loss of immune tolerance to self-antigens playing a part in the development of these conditions. In particular the IL-2 and IL-12 regulatory pathways have been implicated in pre-disposing to an unopposed inflammatory response within the liver. Main immunological themes revolve around loss of immune tolerance leading to T-cell mediated injury, imbalance in the regulation of immune cells and defective immune response to foreign antigens. For PBC and PSC, there is then the added complexity of the consequences of cholestasis on hepato-biliary injury, immune regulation and liver fibrosis. Whilst specific disease causes and triggers are still lacking, AILD arises on the background of collective genetic and environmental risk, leading to chronic and abnormal hepato-biliary immune responses. Effective and more rational therapy will ultimately be developed when the multiple pathways to liver injury are

Pegylated interferon de novo-induce autoimmune haemolytic anaemia in chronic hepatitis C patient.

PubMed