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Background: Dermatitis Herpetiformis (DH) diagnosis relies on direct immunofluorescence (DIF) on skin biopsy. Serology for anti-epidermal transglutaminase antibodies (Anti-TG3 Abs) has attracted interest, being inexpensive and less invasive. However, the available test has variable sensitivity and low specificity in Coeliac Disease (CD) patients without DH. Objective: To evaluate the diagnostic accuracy and reproducibility of a novel quantitative ELISA for the measurement of Anti-TG3 Abs. Methods: ELISA was set-up with recombinant TG3 and a standard curve based on a human recombinant monoclonal IgA anti-TG3. Sera of 57 DH patients, 212 CD patients, 120 patients with non-gluten related gastrointestinal diseases (CTRL) and 168 healthy controls (HC) were tested. Results: The test was reproducible with high sensitivity (91%). Test specificity was high when considering HC (99%) as well as CTRL (98%). Interestingly in CD patients test specificity was agedependent and was higher (97%) in patients ≤ 25 years of age. Limitations: Not all DH were confirmed by DIF. Conclusion: The ELISA test could be used as a screening tool when DH is clinically suspected and may serve as a sole diagnostic test in younger patients. The quantification of Anti-TG3 Abs levels will facilitate the comparison of results from different laboratories.

Coeliac disease is hallmarked by an abnormal immune reaction against ingested wheat-, rye- and barley-derived gluten and the presence of transglutaminase 2 (TG2)-targeted autoantibodies. The small-bowel mucosal damage characteristic of the disorder develops gradually from normal villus morphology to inflammation and finally to villus atrophy with crypt hyperplasia. Patients with early-stage coeliac disease have TG2-autoantibodies present in serum and small-intestinal mucosa and they may already suffer from abdominal symptoms before the development of villus atrophy. Previously, we have shown that intraperitoneal injections of coeliac patient-derived sera or purified immunoglobulin fraction into mice induce a condition mimicking early-stage coeliac disease. In the current study, we sought to establish whether recombinantly produced patient-derived TG2-targeted autoantibodies are by themselves sufficient for the development of such an experimentally induced condition in immune-compromised mice. Interestingly, mice injected with coeliac patient TG2-antibodies had altered small-intestinal mucosal morphology, increased lamina propria cellular infiltration and disease-specific autoantibodies deposited in the small bowel, but did not evince clinical features of the disease. Thus, coeliac patient-derived TG2-specific autoantibodies seem to be sufficient for the induction of subtle small-bowel mucosal alterations in mice, but the development of clinical features probably requires additional factors such as other antibody populations relevant in coeliac disease.

Typical features of celiac disease are small-bowel villus atrophy, crypt hyperplasia, and inflammation which develop gradually concomitant with ingestion of gluten. In addition, patients have anti-transglutaminase 2 (TG2) autoantibodies in their serum and tissues. The aim of this study was to establish whether celiac disease can be passively transferred to mice by serum or immunoglobulins. Serum aliquots or purified immunoglobulins (Ig) were intraperitoneally injected into Hsd:Athymic Nude-Foxn1nu mice for 8 or 27 days. As mice do not have proper IgA transport from peritoneum to blood, sera with a high content of IgG class anti-TG2 antibodies from untreated IgA-deficient celiac patients were used. Mouse sera were tested for celiac disease-specific autoantibodies, and several tissues were analyzed for autoantibody deposits targeted to TG2. Morphological assessment was made of the murine small intestinal mucosa. Injection of celiac disease patient sera or total IgG led to a significant delay in weight gain and mild diarrhea in a subset of mice. The mice injected with celiac patient sera or IgG had significantly decreased villus height crypt depth (Vh/CrD) ratios and celiac disease-specific autoantibody deposits targeted to TG2 in several tissues, including the small intestine. None of these features were observed in control mice. We conclude that administration of IgA-deficient celiac disease patient serum or total IgG induces both deterioration of the intestinal mucosa and clinical features of celiac disease in mice. The experimentally induced condition in the mice injected with patient serum or IgG resembles early developing celiac disease in humans.Celiac disease patient sera or total IgG was injected into athymic mice. A significant delay in weight gain and mild diarrhea was observed. Mice evinced significantly decreased villus height crypt depth ratios. Celiac disease-specific autoantibody deposits were present in several tissues. The condition in mice resembles early stage celiac disease in humans.

Ingestion of dietary gluten in wheat, rye and barley by celiac patients leads to small-bowel mucosal villous atrophy, crypt hyperplasia and massive inflammation, often coupled with clinical symptoms and signs. Currently, the only effective treatment is a strict life-long gluten-free diet excluding all gluten-containing food products. In view of the extremely restricted nature of the diet, new treatment options would clearly be desirable.The improved understanding of celiac disease pathogenesis has enabled researchers to suggest alternative strategies to treat the disorder. This review covers current approaches toward developing an appropriate drug and discusses the possible problems associated with these approaches.Phase II clinical trials are already ongoing to test the efficacy of novel alternative treatments for celiac disease. Before any of the candidates can enter Phase III trials, however, researchers must develop novel reliable non-invasive surrogate markers for intestinal injury and disease activity which also accurately reflect patient-related outcomes. Any novel medication for celiac disease should be as effective and safe as the gluten-free diet, and this constitutes a challenge for drug development. It is thus likely that the first medication entering the market will be supplementary to rather than substitute the gluten-free diet.