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.

Grant Number: 1R21AI187952-01
NIH Institute/Center: NIH
Principal Investigator: John Chang