DOP81 Unaffected ileal transcriptomics in Crohn's disease is associated with the response to anti-TNF therapy

Abstract Background We aimed to assess the gene expression profiles of uninflamed small bowels in patients with Crohn’s disease (CD) identify its accompanying molecular alterations. Methods performed RNA sequencing bowel tissues obtained from 70 ileal CD, and 9 colon cancer (non-CD controls) during resection. Differentially expressed (DEG) analyses were using DESeq2. Gene set enrichment, correlation, cell deconvolution applied modules functionally enriched transcriptional signatures CD. Results A comparison CD non-CD controls revealed that 372 DEGs, 49 protein-coding genes 5 lncRNAs overlapped IBD susceptibility loci. The pathways related immune inflammatory reactions upregulated while metabolic downregulated Compared controls, had significantly higher proportions cells, including plasma cells (P=1.15×10-4), a lower proportion epithelial (P=1.12×10-4). Co-upregulated (M14 module) co-downregulated (M9 identified patients. M14 module was immune-related associated responses anti-TNF therapy. Intestinal tissue transcriptomic analysis 3 independent cohorts, upregulation non-responders at baseline, which predictive response acceptable discrimination ability (area under curve 77~83%). Conclusion differences cellular composition between imply significant alterations, are treatment.