TG6 auto-antibodies in dermatitis herpetiformis

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of gluten sensitivity, in which an autoimmune response is directed against transglutaminase 3 (TG3), an epidermal transglutaminase. TG2 is the autoantigen in celiac disease (CD), defined by the presence of enteropathy, and TG6 is the autoantigen in neurological manifestations of gluten sensitivity. The interplay between B cell responses to these 3 transglutaminases in developing the clinical spectrum of disease manifestations is not completely understood. Also, the individual or combined diagnostic and predictive value of the respective autoantibodies is not fully explored. We examined the prevalence of TG6 antibodies in a cohort of patients with DH. TG6 positivity was found in 13/33 (39%), with IgA detected in 11 patients, IgG in 3, and both in 1. This was significantly higher compared to what is seen in the classic CD cases (14%) in a Finnish population. TG6 positive baseline samples constituted 60% of DH patients with no enteropathy (n = 10), as opposed to 17% positivity in those with overt enteropathy (n = 12; Marsh IIIB). Repeat testing after adherence to a gluten-free diet for 1 year showed reduced titers for TG6 antibodies in 11/13 (85%), whereby 7 patients were now TG6 antibody-negative. Four patients seroconverted and tested positive for TG6 antibodies at one year, due to the ongoing exposure to gluten. We report another patient who presented with neurological manifestations (encephalopathy) leading to the diagnosis of CD, who was intermittently adhering to a gluten-free diet. Serological testing at baseline showed him to be positive for antibodies to all 3 transglutaminases. Eleven years later, he developed DH. He also subsequently developed ataxia and peripheral neuropathy. Although TG3 and TG6 autoantibodies are linked to certain disease manifestations, TG2, TG3, and TG6 autoantibodies can be present across the spectrum of GRD patients and might develop years before onset of symptoms of extraintestinal manifestations. This is consistent with gluten-dependent adaptive immunity being a necessary but not sufficient pretext to organ-specific damage. TG6 antibodies appear to develop more frequently in patients where tolerance to gluten was broken but, either there was no development of the molecular state driving the tissue destruction at the level of the gut, or perhaps more likely, there was more resistance to developing this phenotype

Chronic Gastritis in Dermatitis Herpetiformis: A Controlled Study

Background and Objective. Previous small studies suggest that chronic atrophic gastritis is common in dermatitis herpetiformis (DH). We here examined the frequency and topography of chronic gastritis in 93 untreated DH subjects and in 186 controls with dyspepsia. Methods. Specimens were drawn from the gastric corpus and antrum and examined for atrophy, intestinal metaplasia, and Helicobacter pylori. Duodenal biopsies were taken. Results. Atrophic corpus gastritis was more frequent in DH than in controls (16.0% and 2.7%, resp., P < 0.001); atrophy in the antrum was rare in both groups (3.2% and 1.1%, P = 0.34). Intestinal metaplasia was present in 13 (14.0%) DH and 12 (6.5%) control patients (P = 0.038) and H. pylori in 17 (18.3%) and 17 (9.3%) (P = 0.028), respectively. Small-bowel villous atrophy was seen in 76% of the DH patients, equally in patients with and without chronic gastritis. One DH patient with atrophic gastritis developed gastric cancer. Conclusion. In DH, chronic atrophic gastritis was common in the corpus, but not in the antrum. H. pylori will partly explain this, but corpus atrophy is suggestive of an autoimmune etiology. Atrophic gastritis may increase the risk of gastric cancer. We advocate performing upper endoscopy with sufficient histologic samples in DH

Serum transglutaminase 3 antibodies correlate with age at celiac disease diagnosis

Background: Transglutaminase (TG)2 is the autoantigen in celiac disease, but also TG3 antibodies have been detected in the serum of celiac disease patients. Aims: To investigate the correlations between serum TG3 antibodies and clinical and histological manifestations of celiac disease and to assess gluten-dependency of TG3 antibodies. Methods: Correlations between serum TG3 antibody levels measured from 119 adults and children with untreated coeliac disease and the demographic data, clinical symptoms, celiac antibodies, histological data and results of laboratory tests and bone mineral densities were tested. TG3 antibodies were reinvestigated in 97 celiac disease patients after 12 months on a gluten-free diet (GFD). Results: TG3 antibody titers were shown to correlate with the age at celiac disease diagnosis. Further, negative correlation with TG3 antibodies and intestinal gamma delta+ cells at diagnosis and on GFD was detected. Correlations were not detected with the clinical manifestation of celiac disease, TG2 or endomysial autoantibodies, laboratory values, severity of mucosal villous atrophy, associated diseases or complications. TG3 antibody titers decreased on GFD in 56% of the TG3 antibody positive patients. Conclusion: Serum TG3 antibody positivity in celiac disease increases as the diagnostic age rises. TG3 antibodies did not show similar gluten-dependency as TG2 antibodies. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Dermatitis Herpetiformis Refractory to Gluten-free Dietary Treatment

Dermatitis herpetiformis (DH) is a blistering skin disease, which is regarded as an extra-intestinal manifestation of coeliac disease. Refractory cases of coeliac disease, that do not respond to a gluten-free diet and which carry an increased risk of lymphoma, are well-known in coeliac disease. To determine whether refractory cases of DH with active rash and persistent small bowel atrophy occur we analysed our series of 403 patients with DH. Seven (1.7%) patients, who had been on a gluten-free diet for a mean of 16 years, but who still required dapsone to treat the symptoms of DH, were identified. Of these, one patient died from mucinous adenocarcinoma before re-examination. At re-examination skin immunoglobulin A (IgA) deposits were found in 5/6 refractory and 3/16 control DH patients with good dietary response. Small bowel mucosa was studied at re-examination from 5 refractory and 8 control DH patients and was normal in all 5 refractory and 7/8 control DH patients. One refractory DH patient died from adenocarcinoma, but no lymphoma developed in any of the patients. This study documents for the first time refractory DH, in which the rash is non-responsive to a gluten-free diet, but the small bowel mucosa heals. This differs from refractory coeliac disease, in which the small bowel mucosa does not heal on a gluten-free diet.Peer reviewe

Evaluation of the Human IgG Antibody Response to Aedes albopictus Saliva as a New Specific Biomarker of Exposure to Vector Bites

Aedes-borne viruses like dengue and chikungunya are a major problem in Reunion Island. Assessing exposure to Aedes bites is crucial to estimating the risk of pathogen transmission. Currently, the exposure of populations to Aedes albopictus bites is mainly evaluated by entomological methods which are indirect and difficult to apply on a large scale. Recent findings suggest that evaluation of human antibody responses against arthropod salivary proteins could be useful in assessing exposure to mosquito bites. The results indicate that 88% of the studied population produce IgG to Ae. albopictus saliva antigens in Reunion Island and show that this biomarker can detect different levels of individual exposure. In addition, little cross-reactivity is observed with Aedes aegypti saliva, suggesting that this could be a specific marker for exposure to Aedes albopictus bites. Taken together, these results suggest that antibody responses to saliva could constitute a powerful immuno-epidemiological tool for evaluating exposure to Aedes albopictus and therefore the risk of arbovirus infection