P025 Colonic rather than ileal expression of ITGA4/ITGB7 correlates with local intestinal inflammation in IBD

Abstract Background Lymphocyte trafficking to the inflamed gut is one of hallmarks Inflammatory Bowel Disease (IBD) pathology. Integrin a4b7 and its ligand MADCAM1 play an important role in targeting immune cells bloodstream mucosal tissues blocking this pathway using anti-a4b7 monoclonal antibody Vedolizumab (VDZ) proved be effective treatment IBD. However, VDZ most efficient Ulcerative Colitis (UC) colonic rather than ileal Crohn’s (CD), for which reasons have not been completely understood. Here we sought compare expression ITGA4, ITGB7 tissue biopsies from small large bowel with respect underlying severity inflammation. Methods Differential gene analysis was conducted bulk RNA Sequencing data generated intestine 611 CD 315 UC patients enrolled a multicentred longitudinal Study Prospective Adult Research Cohort IBD (SPARC IBD) obtained Plexus program Foundation. Gene levels were compared across ileal, rectal segments then linked available measures local Results expressed at comparable vs biopsies. Expression significantly increased both moderate severe based on segmental or composite endoscopy score (SES-CD) all segments. ITGA4 similarly moderate/severe patients, whereas only minor changes observed genes Similar findings where ulcerated sigmoid colon cecum as normal appearing inflamed/ulcerated but correlated modified Mayo endoscopic (MMES). Conclusion Our suggests that influx leukocytes via ITGA4/ITGB7 interactions more common distal proximal ileum. This provides possible mechanistic explanation why Further work needed understand differential regulation cell different regions gut.