Su1285 Glycoproteomic Profiling of Serum Markers of Fibrosis in Fibrostenotic Crohn's Disease -An Objective Measure of Intestinal Damage?

Abstract

Introduction: Ulcerative colitis (UC), one of the two main types of chronic Inflammatory Bowel Disease (IBD), is a significant health problem that is characterized by symptomatic periods (flare-up) interspersed with asymptomatic periods (remission). Since there is no cure for UC, the therapeutic goal is to prevent flare-ups and promptly treat them when they occur. Identifying biological and psychological markers that predict flare-up would significantly improve the management of UC by optimizing treatment to prevent flare-up. The aim of this study was to objectively define biopsychomarkers that predict UC flare-up. Methods: 54 UC patients in remission were included in this prospective longitudinal study. UC patients had at least one documented flare-up within the past 12 months and were either taking no IBD medication or were on a stable dose of IBD medication for at least three months prior to enrollment. Baseline information collected included: markers of inflammation and UC disease activity (i.e., stool calprotectin, serum CRP, serum cytokines, UC disease activity index, sigmoidoscopy score, histological score), sigmoid mucosal microarray analysis for mRNA of genes of interest (i.e., 70 genes), markers of stress (i.e., fasting serum ACTH, 24h urinary cortisol, PSQ), quality of life measure (IBDQ), and psychological assessments (i.e., BDI, STAI, MAAS, PHCS). Flare-up was defined as Mayo UC-DAI >2 plus rectal bleeding score ≥2 and sigmoidoscopy score of ≥2. Results: Twenty seven out of 54 UC subjects (50%) flared over a 12-month period. None of the psychological assessments or markers of stress were significant predictors of UC flare-up. Nor were stool calprotectin or serum C-reactive protein (CRP), ACTH, TNFα, or IL10 predictive of flare-up. However, endoscopy score (grade 1), serum IL6, and serum IL8 were significantly different between UC patients with and without flare-up. Analysis of gene expression in mucosal biopsy found eight genes predictive of UC flare-up including inflammatory (IL23R, STAT3, HMGB1), stress (CRHR2), brain-gut axis (NPY), intestinal barrier (TJP1), as well as other (TP53, LRRK2) genes. Furthermore, expression of HMGB1, OCLN (intestinal barrier), and TP53 predicted whether flare-up occurred within 6 or 12 months. Conclusion: Our prospective study found that: (1) stool calprotectin, serum TNFα, ACTH, IL10, urine cortisol, histological score, and psychological measures at baseline did not predict UC flare-up; (2) high serum IL6, low serum IL8, and grade 1 endoscopy score (i.e., loss of vascular pattern) at baseline predicted UC flare-up during the following 12 months; and (3) a characteristic mucosal gene signature predicted early (i.e., within six months) and late (i.e., within 12 months) UC flare-up.