Short gluten challenge in Dermatitis herpetiformis elicits changes in BCR repertoires despite lack of inflammatory signature in transcriptomics 2530

Abstract Description Dermatitis herpetiformis (DH) is a gluten-induced chronic autoimmune skin condition manifesting as itchy blisters in the extremities of the body. It is thought to develop from untreated celiac disease (CeD). Both DH and CeD patients present with autoantibodies against transglutaminase 2 (TG2), and DH patients additionally have transglutaminase 3 (TG3) autoantibodies. DH patients also have TG3-specific IgA deposition in the papillary dermis. Although DH manifests as a rash, it is though that the immune responses responsible for the skin symptoms might originate from the gut. Therefore, understanding transcriptome and B cell receptor (BCR) repertoires of circulating cells in DH could help our understanding on the relation between skin and intestinal symptoms. To understand the skin symptoms and their relation to the intestinal symptoms, we conducted bulk RNA and BCR sequencing of DH patient PBMCs during gluten challenge. Despite little changes in transcriptome, number of unique BCR clonotypes significantly increases after 6 days of gluten challenge. The amount of shared clonotypes between patients is increased on day 6 compared to day 0. These results indicate that 6 day gluten challenge elicit clonal expansion of B cells in DH. These BCRs preferentially use certain light chain genes, which is also known in data from CeD patients. Further analyses on antigen-specific BCRs will shed light on the possible differences between DH and CeD. Topic Categories Basic Autoimmunity (BA)