P0034 Glycosylation as new molecular mechanism underlying Pediatric Inflammatory Bowel Disease

Abstract Background Pediatric Inflammatory Bowel Disease (IBD) can be a highly disabling chronic condition. Genetic, immune and microbial factors have been associated with the development of IBD. Recent studies have shown that changes in glycosylation increase the susceptibility to immune-mediated diseases in adults, including IBD. This study aims to investigate, for the first time in pediatric population, if changes in glycosylation play a role in the immunopathogenesis of IBD, envisioning the identification of novel biomarkers and therapeutic targets. Methods We designed a cross-sectional study in which blood samples and fresh colonic biopsies from pediatric patients, either with Crohn’s Disease (CD) or Ulcerative Colitis (UC) or without IBD, were collected at the time of colonoscopy or outpatient visit in a tertiary hospital. T lymphocytes were isolated from colonic tissue and blood, and their glycosylation profile was analyzed by fluorescence-activated cell sorting using specific lectins that recognize different glycans structures and surface antibodies as markers of immune cells (CD45, CD4, CD8). Results A total of 80 participants were included, 24 without IBD and 56 with IBD. Among the IBD patients, 23 were diagnosed with Ulcerative Colitis (UC) and 33 with Crohn's Disease (CD). We observed that T lymphocytes from patients with CD exhibit a glycosylation profile alteration distinct from that seen in patients with UC and children without IBD, both at the level of the colon mucosa and in circulation (blood). The levels of a specific free glycan in peripheral blood circulation were higher in patients with Crohn's Disease compared to those with UC and non-IBD (p<0.05). Conclusion Our data suggest that CD patients may have a distinctive glycosignature that can be detected in circulation. This may represent a promising tool to discriminate CD patients from UC and non IBD, thus reducing the need for invasive exams in these patients. Overall, our findings may contribute to the identification of a novel diagnostic biomarker with clinical impact in decision-making algorithms, as well as therapeutic targets to improve disease control.