A Blood-based Transcriptomic Signature Stratifies Severe Crohn's disease and Defines Potentially Targetable Therapeutic Pathways

Surgical resection in severe Crohn's disease is a common consequence of therapeutic failure. We identified 2 severe CD subtypes: one similar to non-IBD subjects, the other exhibited a mucosal-like gene signature, altered T-cell subsets, severity features and decreased pro-inflammatory expression post-surgery. These findings may identify targets for CD subtype-specific therapeutic and biomarker development. CD3+ T-cells were purified from paired blood and mucosa from 100 CD and 17 non-inflammatory bowel disease (IBD) subjects requiring surgery. Longitudinal samples (n=49) were collected 4-13 months postoperatively. Expression profiles were generated by RNA-Seq. Transcriptional Risk Scores (TRS), T-cell subset deconvolution, gene pathway and kinase analyses were performed.