OP17 A molecular measure of inflammation in IBD patients based on transcriptional profiles from 2495 intestinal biopsies
R. Huang1, H. Irizar2, R. Kosoy3, W-m. Song3, A. Dinarzo3, K. Hao3, J. Rogers4, A. Atreja4, M. Mahajan3, A. Stojmirovic5, J. Perrigoue5, C. Brodmerkel5, S. Plevy5, J. Friedman5, J-F. Colombel4, M. Dubinsky4, B. Sands4, E. Schadt3, A. Kasarskis3, B. Losic3, C. Argmann3, M. Suarez-Farinas1,3
1Icahn School at Mount Sinai, Department of Population, Health Science and Policy, New York, USA, 2University College of London, London, UK, 3Icahn School at Mount Sinai, Department of Genetics and Genomic Science, New York, USA, 4Icahn School at Mount Sinai, Department of Medicine, Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center, New York City, USA, 5Janssen Research and Development, Janssen Biotech, Johnson and Johnson, Spring House, USA
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.
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
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;
Association of MIS with histological (A), endoscopic (B) and clinical (C) IBD severity. Means (black dots) and CI (blue)
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 subsetting, identify sub-clinical disease, predict flares or therapeutic response. Furthermore, MIS can be used to regress the inflammation component, revealing novel non-inflammatory mechanisms.
1. Hänzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data.
2. D’Haens GR, Geboes K, Peeters M,
3. Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C,