DOP29 Elevation of a novel blood-based gene signature in a severe Crohn’s disease (CD) subtype preceding surgery defines and predicts a post-surgical decrease in pro-inflammatory pathway activation
R. Gonsky1, P. Fleshner2, G. Botwin1, E. Biener-Ramanujan1, D. McGovern1, S. Targan1
1Cedars Sinai Medical Center, Inflammatory Bowel and Immunobiology Research Institute, Los Angeles, California, USA, 2Cedars Sinai Medical Center, Department of Surgery, Los Angeles, CA, USA
CD is defined by transmural inflammation leading to inflammatory, stricturing and/or penetrating phenotypes. Identifying underlying molecular pathways and distinct disease subsets is critical for improved prognostics, therapeutics and biomarker discovery.
CD3+ T cells were purified from paired blood and mucosal tissue from 101 CD and 17 non-IBD subjects requiring surgery. Longitudinal samples (
Unsupervised clustering of peripheral T-cell gene expression at surgery revealed 2 CD profiles: Expression from cluster1, labelled CD-PBT (63%), clustered tightly with the non-IBD group. In cluster2, expression shifted from a peripheral toward a mucosal profile, labelled CD-PBmu(cosal) (37%). CD-PBmu was defined by differentially expressed genes (DEG) (1944 DEG,
Severe CD can be stratified into 2 subtypes based on peripheral T-cell gene expression. Circulating T cells from CD-PBmu exhibit a mucosal-like gene signature, altered T-cell subset composition, clinical features of severity and decreased pro-inflammatory gene expression post-surgery. These findings hold potential to identify targets for CD subtype-specific therapeutic development. The 44-gene classifier overlapped with multiple paediatric CD datasets, suggesting the potential application of these findings for treatment stratification early in the disease process.