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- What is elafin and does it play a role in gluten related disorders?
What is elafin and does it play a role in gluten related disorders?
Dr Elena Verdu
Dr Elena Verdu studied medicine at the University of Buenos Aires. She then obtained a fellowship from the Swiss National Foundation, Lausanne. During her doctoral work at the Czech Academy of Science she gained experience in animal models of inflammatory bowel disease, intestinal microbiota, and gnotobiotic work. As a post doctoral fellow at McMaster University, Canada she worked on the role of probiotics in animal models of gut functional diseases. Dr Verdu became a faculty member at McMaster University in 2006 and her research focuses on the pathophysiology of inflammatory and functional gastrointestinal disorders. Through her career, Dr Verdu has received several research awards including the Canadian Celiac Association’s J.A. Campbell Research Award, Master’s in Gastroenterology by the American Gastroenterology Association and Young Investigator Award by the Canadian Gastroenterology Association.
Elafin is a human serine protease inhibitor that has potent inhibitory capacity against various forms of pro inflammatory elastases as well as proteinase-3. Elafin is expressed throughout the epithelium of the gastrointestinal tract but it has been shown to be decreased in the colon of inflammatory bowel disease patients. Moreover elafin administration prevents inflammation in murine models of experimental colitis. The role of elafin in gluten related disorders is unknown. We therefore investigated the role of elafin in coeliac disease using human small intestinal tissues and in vitro assays of gliadin deamidation. We also investigated potential beneficial effects of elafin in a mouse model of gluten sensitivity. We found that elafin expression in the small intestinal epithelium was lower in patients with active coeliac disease compared to control patients. In vitro, elafin significantly slowed the kinetics of the deamidation of the 33-mer peptide to its more immunogenic form. Treatment of gluten sensitive mice with elafin delivered by a L. lactis vector normalized inflammation, improved permeability and maintained ZO-1 expression. The identification of a molecule (elafin) that is altered in the small intestine of active coeliac disease patients and that reduces deamidation of gliadin peptide, and that has barrier enhancing effects in the small intestine, will help increase understanding of the pathophysiology of coeliac disease and promote development of new supportive treatments for gluten related disorders.