P069 Elevated adaptive immune responses to multiple Lachnospiraceae bacterial flagellins in therapy-naïve pediatric CD patients are associated with distinct immune pathology

Abstract Background In inflammatory bowel disease (IBD), including Crohn’s (CD) and ulcerative colitis (UC), CD4+ T cell-responses to unknown microbial antigens drive intestinal inflammation. Both hypo- or hyperactive anti-microbial innate immunity may underlie these pathogenic T-cell responses. Previously, IgG responses Lachnospiraceae flagellins were detected in spontaneously colitic mice with an immune defect adult CD patients complicated disease. However, whether occur therapy-naïve pediatric they relate hyperresponsiveness is unknown. We hypothesize that, at diagnosis, a subgroup of has elevated anti-Lachnospiraceae flagellin concomitant flagellin-specific associating insufficient immunity. Methods Plasma reactivity 20 from that colonize mouse human gut was measured IBD (CD n=49; UC n=16), non-IBD (n=12) age-matched healthy controls (HC n=17). divided two groups: ‘flagellin-hi’ (elevated 11-20 flagellins) ‘flagellin-lo’ 0-10 flagellins), whose immunological clinical profiles compared. Results The proportion flagellin-hi higher (41%) compared (6%), (8%) HC (6%). patients, activity score, CRP ESR did not reactivity. Compared flagellin-lo had increased frequencies gut-homing (CD38+CD62Lneg) circulating cells. Crucially, high Although anti-flagellin associated flagellin-specific- gut-homing- the circulation, it very limited cell infiltration, epithelial damage phosphorylated NFκB colonic biopsies on histology. Moreover, plasma concentration EN-RAGE, neutrophil-derived protein, decreased -lo patients. Conclusion sum, Lachnospiraceae-derived flagellins. While have cells, lower histological activation, possibly suggesting activation and/or infiltration. Together, our data raise question enhanced adaptive response be driven by local