OP17 A molecular measure of inflammation in IBD patients based on transcriptional profiles from 2495 intestinal biopsies

• Published in: Journal of Crohn's and colitis 2019-01, Vol.13 (Supplement_1), p.S011-S012
• Main Authors: Huang, R, Irizar, H, Kosoy, R, Song, W-m, Dinarzo, A, Hao, K, Rogers, J, Atreja, A, Mahajan, M, Stojmirovic, A, Perrigoue, J, Brodmerkel, C, Plevy, S, Friedman, J, Colombel, J-F, Dubinsky, M, Sands, B, Schadt, E, Kasarskis, A, Losic, B, Argmann, C, Suarez-Farinas, M
• Format: Article
• Language: English
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjy222.016

Abstract Background Endoscopy, histology, and biomarker measures of inflammation have limitations of sensitivity, specificity, reproducibility, and range in evaluating inflammatory bowel disease (IBD). We explored whole transcriptome gene expression to define molecular scores of gut inflammation. These scores are applicable to both Crohn’s disease (CD) and ulcerative colitis (UC), enabling more granular, continuous measures across multiple states and location of disease. Methods We present a molecular characterisation of IBD based on the transcription profiles of 719 endoscopically defined inflamed (Inf) and 1776 non-inflamed (NInf) intestinal biopsies from 498 CD, 419 UC patients in the Mount Sinai Crohn’s and Colitis Registry (MSCCR) during endoscopy. Genes differentially expressed between Inf and NInf biopsies were used to generate a biopsy-level molecular inflammation score (MIS) via gene set variation analysis.1 Results MIS was strongly associated with histological biopsy scores for CD (GHAS2) and UC (Nancy Index3) and independent of inflammatory status (Inf B = 3.1, NInf B = 2.73; p > 0.05) (Figure 1A), MIS of Inf biopsies was higher than NInf within the same histological score, indicating that MIS describes a broader range of inflammation signal than histologic assessment. MIS was also associated with endoscopically defined severity (SES-CD and Mayo-endo for UC); capturing the gradient from mild, moderate, to severe disease (Figure 1B). Association of MIS with clinical disease severity was significant for Inf biopsies for continuous measures (HBI for CD B = 0.65, p < 0.01; SCCAI for UC B = 1.94, p < 0.01) and could also differentiate between HBI and SCCAI defined active and inactive subsets (UC d = 11.5, p < 0.01; CD d = 5, p < 0.01). This was not the case for NInf biopsies (Figure 1C), indicating that the clinical scores track with inflammation but not with homeostatic features of the gut. Abstract OP017 Association of MIS with histological (A), endoscopic (B) and clinical (C) IBD severity. Means (black dots) and CI (blue) Conclusions We generated a transcriptionally based intestinal inflammation score in IBD patients, which provides an objective quantification of disease state in IBD-relevant tissues. MIS scores are associated with features captured by histological, endoscopic, and clinical evaluations, but do so with a greater dynamic range, and as a common metric for CD and UC. Further work will explore whether MIS may improve patients subsettin