Serum Anti-endomysial Antibodies Research Articles

The Articulate Canker-Aphthous Ulcer

Aphthous ulcer occurs as a frequent, idiopathic, painful, singular, multiple or reoccurring oral ulceration. Of obscure aetiology, oral trauma, stress, anxiety, diverse systemic diseases as coeliac disease, Crohn’s disease, Behçet’s syndrome, reactive arthritis or infection with human immune deficiency virus (HIV), drugs such NSAIDs, β-blockers, angiotensin converting enzyme (ACE) inhibitors, deficiencies of vitamins and trace elements as zinc, iron, B12, folate or sensitivity to food and chemicals may engender the ulcer. Contingent to magnitude, aphthous ulcer is subcategorized into minor ulcer, major ulcer or herpetiform ulcer. Aphthous ulcer manifests upon non-keratinized oral mucosa as a well circumscribed, centric, necrotic ulcer circumscribed by a grey, fibrinous exudate and an erythematous halo. The ulcer requires a segregation from contact dermatitis, lichen planus, oral carcinoma, infection with herpes simplex virus (HSV), various drug induced lesions or autoimmune diseases. Aphthous ulcer can be evaluated with clinical examination, complete blood count with nutritional deficiencies of iron, folate or vitamin B12, neutropenia, serum anti-endomysial antibodies and transglutaminase (tTg-IgA) for coeliac disease and investigations for HIV. Cogent therapeutic options are local anaesthetics, coating or occlusive agents as bismuth subsalicylate, sucralfate, 2-octyl cyanoacrylate, bio-adherent emollient pastes, oral antiseptics as chlorhexidine gluconate, hydrogen peroxide, antiinflammatory agents as glucocorticoids, metalloprotease inhibitors, antimicrobials as tetracycline, doxycycline, minocycline, honey, immunomodulatory agents as amlexanox, colchicine, cyclosporine, cyclophosphamide, dapsone, methotrexate, montelukast, thalidomide or retinoids.

Are ESPGHAN "biopsy-sparing" guidelines for celiac disease also suitable for asymptomatic patients?

In 2012, European Society of Pediatric Gastroenterology, Hepatology, and Nutrition published novel guidelines on celiac disease (CD) diagnosis. Symptomatic children with serum anti-transglutaminase (anti-tTG) antibody levels ≥10 times upper limit of normal (ULN) could avoid duodenal biopsies after positive HLA test and serum anti-endomysial antibodies (EMAs). So far, both asymptomatic and symptomatic patients with anti-tTG titer <10 times ULN should undergo upper endoscopy with duodenal biopsies to confirm diagnosis. The aim of this study was to assess the accuracy of serological tests to diagnose CD in asymptomatic patients. We retrospectively reviewed data of 286 patients (age range: 10 months to 17 years) with CD diagnosis based on elevated titer of anti-tTG, EMA positivity, and histology. All patients were distinguished between symptomatic and asymptomatic; histological lesions were graded according to the Marsh-Oberhuber (MO) criteria. Fisher exact test was applied to analyze both groups in terms of diagnostic reliability of serological markers. A total of 196 patients (68.53%) had anti-tTG titers ≥10 times ULN. Among them, a group of 156 patients (79.59%) also had symptoms suggestive of CD ("high-titer" symptomatic); of these, 142 patients (91.02%) showed severe lesion degree (3a, 3b, 3c MO). Conversely, 40 out of 196 patients (20.40%) were asymptomatic ("high-titer" asymptomatic) and 37 patients (92.5%) of them showed severe lesion degree (3a, 3b, 3c MO). No difference in histological damage was found between "high-titer" symptomatic and "high-titer" asymptomatic children (Fisher exact test, P=1.000). If confirmed in large multicenter prospective studies, the "biopsy-sparing" protocol seems to be applicable to both symptomatic and asymptomatic patients with anti-tTG titer ≥10 times ULN, positive EMA, and HLA-DQ2/DQ8.

High Incidence of Celiac Disease in Patients with Systemic Sclerosis

To evaluate the presence of celiac disease in patients with systemic sclerosis (SSc). The association of autoimmune diseases with celiac disease has been reported, but few publications deal with the combination of SSc and celiac disease. We investigated the presence of anti-tissue transglutaminase (anti-tTG) antibodies and serum antiendomysial antibodies (anti-EMA) in 50 patients with SSc. All subjects were on a gluten-containing diet. Duodenal mucosa histology and biopsy culture were performed in anti-tTG-positive patients; anti-EMA and IgA, IgG1 anti-tTG were detected in culture supernatants. The incidence of celiac disease in patients with SSc was found to be 8%. Serum anti-tTG antibody-positive results were detectable in 5 out of 50 patients with SSc, but only in 4 of them was the diagnosis confirmed by histological results (Marsh classification). Our data show an increased prevalence of celiac disease in patients with SSc.

Anti-endomysial antibody of IgG1 isotype detection strongly increases the prevalence of coeliac disease in patients affected by type I diabetes mellitus

A strong association between type 1 insulin-dependent diabetes mellitus (IDDM1) and coeliac disease (CD) is well documented, but it is known that prevalence values are underestimated. Serum anti-endomysial antibodies (EMA), considered diagnostic for CD because of their high sensitivity and specificity, belong to the IgA class, but the existence of EMA of IgG1 isotype in the presence or absence of IgA deficiency was reported. In order to re-evaluate the occurrence of CD in IDDM1 patients we performed a screening in IDDM1 patients using EMA of both isotypes. Ninety-four adults affected by IDDM1 (unaffected by CD before enrolling) were enrolled and 83 blood donors as controls. All subjects were on a gluten-containing diet. Histology and biopsy culture were performed. EMA IgA and IgG1 in sera and culture supernatants were detected. Serum EMA were positive in 13 of 94 IDDM1 patients (13.8%). Six of 13 presented IgA-EMA, seven of 13 presented IgG1-EMA. No EMA were found in the control population. Total intestinal atrophy was found in all six patients with serum IgA-EMA and in five of seven with serum IgG1-EMA. Diagnosis of CD was confirmed by histology and organ culture in all 13 patients with serum EMA. The prevalence of CD in the patients affected by IDDM1 was 6.4% for IgA-EMA-positive and 7.4% for IgG1-EMA-positive patients. We confirmed the prevalence of CD in the IDDM1 population obtained with IgA-EMA screening only (6.4%). This prevalence value increases dramatically to 13.8% when IgG1-EMA are also used in the screening. We conclude that IgG1-EMA should also be sought whenever an IDDM1 patient undergoes screening for CD.

Screening for celiac disease in non-Hodgkin's lymphoma patients: a serum anti-transglutaminase-based approach.

Several studies have shown the existence of an association between celiac disease (CD) and non-Hodgkin's lymphoma (NHL). Our aim was to evaluate the usefulness of the serum anti-tissue transglutaminase (anti-tTG) antibody assay in screening for CD in consecutive NHL patients. In all, 80 consecutive patients (median age 61 years) with a new diagnosis of NHL were included. To compare the frequency of CD and of positive results for the anti-tTG assay, we enrolled 500 blood donors. In all patients serum anti-tTG was determined with two different ELISA: one based on tTG from guinea pig (gp-tTG) and the other based on human recombinant t-TG (h-tTG) as the antigens. Serum anti-endomysial antibodies (EmA) were also assayed. Subjects with positive serum EmA and/or anti-tTG underwent intestinal biopsy for histology study, HLA-DQ phenotype determination, and serum anti-gliadin (AGA) assay. Eight of 80 (10%) NHL patients were positive for anti-tTG ELISA--two of these exclusively for anti-gp-tTG and six for anti-h-tTG (7.5%). None of the 80 NHL patients were positive for serum EmA. The frequency of anti-tTG positivity in the blood donor controls was 2/500 (0.4%), significantly lower than that observed in the NHL patients (P < 0.0001). Both these blood donors were found to have CD. Only in one anti-h-tTG-positive NHL patient was there intestinal mucosa atrophy, and follow-up confirmed a CD diagnosis (CD frequency in NHL patients is 1.2%; versus blood donors: P = 0.4). In all the other seven anti-tTG-positive NHL patients a normal intestinal architecture was found, although, inflammatory infiltration of the lamina propria was observed in four patients. No anti-tTG-positive NHL patients, including the subject diagnosed as having CD, had a family history of CD, and all had normal weight and no signs of malabsorption. Anti-tTG false positive results were associated with a higher frequency of serum autoantibody positivity and T-cell type NHL. In conclusion, NHL patients the anti-tTG assay often gives discordant data with the EmA assay, with a high frequency of anti-tTG false positive results for CD diagnosis.

Antiendomysial antibody detection in fecal supernatants: in vivo proof that small bowel mucosa is the site of antiendomysial antibody production

OBJECTIVES: Serum antiendomysial antibodies (EMAs), highly sensitive and specific serological markers of celiac disease (CD), are detectable in culture media of biopsy samples from CD patients. This finding can be considered an in vitro evidence that intestinal mucosa is a site of EMA production. To confirm this finding, we investigated the presence of EMAs and of anti-tissue transglutaminase (anti-tTG), recently identified as the autoantigen of the EMA, in fecal supernatants of CD patients. METHODS: Twenty-one newly diagnosed CD patients, 10 treated CD patients on a gluten-free diet, and 14 control disease patients on a gluten-containing diet were enrolled. Twenty-four-hour stool collections and fecal supernatants were obtained from all patients in the study. Biopsy cultures were also performed. IgA EMAs were detected in sera, culture media, and fecal supernatants. IgA, IgG, IgM, and IgE antigliadin antibodies (AGAs) and IgA anti-tTG antibodies were measured in fecal supernatants. The weights, water content, and pHs of the 24-h stool collections were also measured. RESULTS: In all untreated CD patients EMAs were detectable in sera, culture media, and fecal supernatants. In treated CD patients, EMAs were detected only in culture media after in vitro gliadin challenge. No EMAs were detected in controls. Anti-tTG levels were higher in untreated CD patients than in treated CD patients and controls. IgA AGA levels were higher in untreated CD patients than in treated CD and control patients, whereas IgM AGAs were higher in both untreated and treated CD patients than in controls. No statistically significant differences were observed for IgG and IgE AGAs among the above-mentioned populations. Fecal weights, water content, and pHs were higher in untreated CD than in control patients. CONCLUSIONS: The presence of EMAs in fecal supernatants represents the in vivo proof that intestinal mucosa is a site of EMA production. Furthermore, EMA detection in the stools could be a simple and useful additional tool to clarify diagnosis in the patchy conditions of CD.

The prevalence and clinical characteristics of celiac disease in juvenile diabetes in Wisconsin.

The relationship between celiac disease and juvenile diabetes has long been known. Only a single study in the United States, from Buffalo, New York, has reported the prevalence of celiac disease in a pediatric diabetic population. This study was conducted to determine the prevalence and clinical presentation of celiac disease in children and adolescents with juvenile diabetes in Wisconsin, USA, using serum antiendomysial antibody as a screening test. Two hundred eighteen patients with diabetes (113 males; age range, 4-21 years) and 117 age-and gender-matched control participants were tested for immunoglobulin A endomysial antibody. Patients with positive results were offered a small bowel biopsy. A questionnaire regarding abdominal pain, diarrhea, and growth failure was completed by the parents. Seventeen of 218 diabetic patients (7.7%) had positive endomysial antibody. All control participants had negative results for the endomysial antibody. Small bowel biopsy was performed in 14 patients. Ten patients had villous atrophy. In one patient without villous atrophy, a repeat biopsy 2 years later showed villous atrophy, and two patients had increased intraepithelial lymphocytes without villous atrophy. Seventy percent of the patients with celiac disease were asymptomatic. The reported symptoms were abdominal pain and diarrhea (n = 1) and growth failure (n = 2). Two patients with celiac disease had Down syndrome. The prevalence of celiac disease in children with juvenile diabetes in Wisconsin is at least 4.6%, which is comparable with European and Canadian studies. Because patients without villous atrophy may have latent celiac disease, the prevalence may be even higher. All children with juvenile diabetes should be screened for celiac disease.

The Prevalence and Clinical Characteristics of Celiac Disease in Juvenile Diabetes in Wisconsin

ABSTRACTBackgroundThe relationship between celiac disease and juvenile diabetes has long been known. Only a single study in the United States, from Buffalo, New York, has reported the prevalence of celiac disease in a pediatric diabetic population. This study was conducted to determine the prevalence and clinical presentation of celiac disease in children and adolescents with juvenile diabetes in Wisconsin, U.S.A., using serum antiendomysial antibody as a screening test.MethodsTwo hundred eighteen patients with diabetes (113 males; age range, 4–21 years) and 117 age‐and gender‐matched control participants were tested for immunoglobulin A endomysial antibody. Patients with positive results were offered a small bowel biopsy. A questionnaire regarding abdominal pain, diarrhea, and growth failure was completed by the parents.ResultsSeventeen of 218 diabetic patients (7.7%) had positive endomysial antibody. All control participants had negative results for the endomysial antibody. Small bowel biopsy was performed in 14 patients. Ten patients had villous atrophy. In one patient without villous atrophy, a repeat biopsy 2 years later showed villous atrophy, and two patients had increased intraepithelial lymphocytes without villous atrophy. Seventy percent of the patients with celiac disease were asymptomatic. The reported symptoms were abdominal pain and diarrhea (n = 1) and growth failure (n = 2). Two patients with celiac disease had Down syndrome.ConclusionsThe prevalence of celiac disease in children with juvenile diabetes in Wisconsin is at least 4.6%, which is comparable with European and Canadian studies. Because patients without villous atrophy may have latent celiac disease, the prevalence may be even higher. All children with juvenile diabetes should be screened for celiac disease.

Celiac disease screening: exploring the iceberg with salivary antigliadin antibodies.

Celiac disease screening: exploring the iceberg with salivary antigliadin antibodies.

13 EMBRYONIC CELIAC ANTIGENS (ECA).

The antigens reactive to serum anti-endomysial antibodies and anti-reticulin antibodies were isolated from human placenta following our observation that sera from patients with celiac disease (CD) binds to placenta tissue sections. We designated the antigens as “Embryonic Celiac Antigens” (ECA). Microscopic evaluation of placenta tissue sections indicate that the antigens were expressed on the cell membrane and cytoplasm of the trophoblast cells. Placental cells grown in primary culture also express the ECA. However, ECA was not found in the culture media. Proteins were extracted from lysed cultured cells, and identified by SDS-PAGE gel electrophoresis and western blotting. Nine protein molecules were bound to the IgA of CD patients. The molecular weights ranged from 22kd - 110kd. High pressure liquid chromatography (HPLC) was used to purify these single proteins. 110kd protein inhibited binding of CD patients IgA to rat kidney (reticulin like antigen). The 65kd protein, on the other hand, inhibited the binding of IgA to the monkey esophagus (endomysium like antigen). Both protein molecules had 60% of cross inhibition activity. The 110kd protein is a heat labile protein and tends to break down to a 55kd molecule without loosing its activity. Low molecular weight proteins (ranging 22kd-45kd) inhibited binding of celiac patient sera to gliadin. High resolution two dimensional electrophoresis demonstrated that the above antigen have isoelectricpoint between 5.1 - 5.9 ECA (110kd; 65kd and 55kd). Protein isolation method; Proteins collected from the cultured placental cell lysate were applied to a DEAE sephadex column and subsequently to Gel Chromatography Sephacryl S-200 HR Column. The ECA does not bind to the IgA or IgG contained in the sera of normal patients, those with inflammatory bowel disease or other immunologic conditions. These findings indicate that celiac antigens are expressed during fetal development. Their investigation may offer insight into the pathomechanism of celiac disease and provide a new tool for diagnosis of the condition.

Incidence of celiac disease identified by the presence of serum endomysial antibodies in children with chronic diarrhea, short stature, or insulin-dependent diabetes mellitus

We determined the incidence of celiac disease in the western New York area to be 1.29 per 10,000 live births. Celiac disease occurred in 29 children with gastrointestinal symptoms. Two children (1.7%) of 117 with short stature and 10 (4.0%) of 211 with diabetes mellitus had serum anti-endomysial antibodies. We conclude that the incidence of childhood celiac disease in our area is much less than that reported in Europe.