Small intestinal inflammation drives granulocyte activation in the pathogenesis of dermatitis herpetiformis 2330

Abstract Description Dermatitis herpetiformis (DH) is a primary extraintestinal manifestation of coeliac disease (CeD). Neutrophils and dermal deposits of IgA are closely linked to skin pathogenesis in DH, and granulocytes are often observed in the small intestine of CD patients with gut enteropathy. We are investigating the role of the small intestinal inflammation as driver of granulocyte activation during active skin pathogenesis. Using transcriptomics and histological methods, we assess granulocyte infiltration and activity in the small intestine and skin of untreated DH and CD patients at diagnosis and after one year on a gluten-free diet. We also examine samples from GFD-treated DH patients before a gluten challenge and after relapse. Flow cytometry and quantitative PCR are used to characterize the circulating granulocyte population. Preliminary findings show neutrophils and eosinophils in the gut and skin of untreated DH patients, as well as in treated patients following a gluten challenge. Granulocytes are mostly absent in both tissues on a GFD. Large neutrophilic abscesses, characteristic of DH skin, are not present in the small intestine. The presence of neutrophils in the small intestine of DH patients suggests a role in disease progression involving both the gut and skin. We are currently studying if there is a possible link between neutrophil populations in these two compartments. Topic Categories Immune Mechanisms of Human Disease (HUM)