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Elafin in Intestinal Barrier Fortification: A Potential Adjuvant Therapy for Gluten Intolerance

Wiepjes, MC;

Background: The intestinal barrier plays an important role in protecting the internal
milieu from potentially harmful substances within the intestinal lumen. A breakdown in
the protective capacity of this barrier has been implicated as a contributing factor in the
development of gastrointestinal diseases such as inflammatory bowel disease (IBD),
irritable bowel syndrome (IBS), and celiac disease. Celiac disease and other, milder forms
of gluten intolerance such as gluten sensitivity (GS), are triggered by the passage of
gluten peptides across the intestinal barrier. Modulation of the barrier therefore represents
an important therapeutic target for limiting uptake of gluten in celiac disease and GS.
Elafin is a potent serine protease inhibitor that is abnormally expressed in patients with
IBD. Administration of elafin in murine models of colitis has been found to reduce
disease severity although the mechanism of this protective effect remains elusive. It is
unknown if abnormal expression of elafin plays a role in the development of celiac
disease or GS.

Study Objectives: Given the promising results of elafin therapy in murine models of
IBD, I sought to investigate if elafin therapy could attenuate markers of gliadin
sensitization in two gluten-sensitive mouse models: HCD4/DQ8 and NOD/DQ8 mice. I
also sought to explore potential mechanisms through which elafin may enact its protective
effect within the gut.