Inflammatory Bowel Diseases: genetic and functional approaches in the NGS era

Inflammatory Bowel Diseases (IBDs) are a group of pathologies characterized by chronic inflammation of the gastrointestinal tract. The two main types of IBDs are Crohn’s disease and ulcerative colitis, which differ for the localization and intestinal wall layers interested by the inflammation. During the last decades, IBDs incidence is increased, especially in the case of pathologies with an onset before 6 years of age, namely Very Early Onset IBDs (VEO-IBDs). Various factors have been investigated for their role in IBD etiology, thus it is still unclear; environmental factors like breastfeeding, diet, smoke have been related to IBDs, but also genetic predisposition has been pointed out as an important element. In this work we wanted to evaluate genetic variants in patients with IBDs, using clinical exome sequencing (CES) for non-VEO patients and whole exome sequencing (WES) for VEO patients. We found different variants reported in literature to be risk factors for IBD. Moreover, we focused on a VEO patient with a novel mutation on IL-10RA gene, assessing the functional defect through phosphorylation assay, and evaluating Th17 and Treg population. We also evaluated Lag3+CD49b+ Tr1 cells, which produce large amounts of IL-10, and a subset expressing both Foxp3 and Rorγt, reported to be important for intestinal inflammation.