Abnormal MUC1 Expression as a Biomarker for Pouchitis

Abstract

Introduction: Pouchitis is common among patients with ulcerative colitis (UC) and ileal-anal pouch anastomosis (IPAA). Healthy epithelial cells express low levels of the fully glycosylated MUC1 glycoprotein. In inflammation, MUC1 becomes overexpressed and hypoglycosylated, interfering with the mucus barrier and perpetuating inflammation. Our aim is to determine patterns of abnormal MUC1 expression in pouch mucosa of patients with UC after IPAA with varying degrees of pouchitis compared to mucosa from patients with familial adenomatous polyposis (FAP) with IPAA and no pouchitis.

Methods: Archived biopsies of J-pouches were identified and stained to detect the abnormal hypoglycosylated MUC1. Each slide was graded for quantity and intensity of the abnormal MUC1 staining (both scored 0-4) by 3 team members blinded to the clinical information. Grading of inflammation was performed based on adaptation of the Nancy Histological Index. Data are expressed as median and interquartile range, and comparison was done through non-parametric tests to calculate p-value.

Results: Tissue was analyzed from 4 FAP/IPAA (without pouchitis) and 87 patients with UC/IPAA and varying degrees of pouchitis; 19 no pouchitis, 27 mild, 36 moderate, and 5 severe pouchitis. There was almost no abnormal hypoglycosylated MUC1 expression among patients with no pouchitis, FAP, or UC. Patients with UC/IPAA had significantly more abnormal MUC1 expression in J-pouch ileal tissue that increased with the degree of pouchitis.

Conclusions: Abnormal hypoglycosylated form of MUC1 in ileal biopsies of patients with UC and pouchitis was overexpressed and proportional to the degree of inflammation. Hypoglycosylated MUC1 may serve as a biomarker of more severe pouchitis.

Keywords: MUC1; Pouchitis; Ulcerative colitis.