Immune adaptations in acute pouchitis

ABSTRACT The inflammatory bowel diseases (IBD) are chronic intestinal disorders that are categorized as one of two subtypes, Crohn’s disease (CD) and ulcerative colitis (UC). Approximately 30% of patients with UC require a proctocolectomy with ileal pouch-anal anastomosis (IPAA), and up to 50% of IPAA patients develop an inflammatory condition called pouchitis within 2 years of creation of the pouch. Many patients with acute pouchitis initially have symptomatic resolution with a course of antibiotics; however, 50-90% of patients have at least one recurrence and 30% of patients will develop chronic pouchitis, many of whom will be refractory to antibiotics. Currently, there are no reliable biomarkers that can predict whether or not a patient will develop pouchitis, nor are there any FDA-approved therapies specifically for pouchitis. Here we propose to apply single-cell RNA- sequencing and spatial transcriptomics to elucidate the immunologic changes that occur in the ileal pouch in ulcerative patients who develop pouchitis compared to those who do not. Elucidating early changes in immune subsets and transcriptional signatures prior to overt development of pouchitis may enable identification of previously unknown biomarkers, nomination of new therapeutic targets, and discovery of novel approaches to prevent pouchitis.