Discerning Endoscopic Severity of Inflammatory Bowel Disease by Scoping the Peripheral Blood Transcriptome.

Background and Aims: Ulcerative colitis (UC) and Crohn's disease (CD) are chronic inflammatory bowel diseases (IBDs) with an incompletely understood etiology and pathogenesis. Identification of suitable drug targets and assessment of disease severity are crucial for optimal management. Methods: Using RNA sequencing, we investigated differential gene expression in peripheral blood samples from IBD patients and non-inflamed controls, analyzed pathway enrichment, and identified genes whose expression correlated with endoscopic disease severity. Results: Neutrophil degranulation emerged as the most significant pathway across all IBD sample types. Signaling by interleukins was prominent in patients with active intestinal inflammation but also enriched in CD and UC patients without intestinal inflammation. Nevertheless, genes correlated to endoscopic disease severity implicated the primary cilium in CD patients and translation and focal adhesion in UC patients. Moreover, several of these genes were located in genome-wide associated loci linked to IBD, cholesterol levels, blood cell counts, and levels of markers assessing liver and kidney function. These genes also suggested connections to intestinal epithelial barrier dysfunction, contemporary IBD drug treatment, and new actionable drug targets. A large number of genes associated with endoscopic disease severity corresponded to noncoding RNAs. Conclusion: This study revealed biological pathways associated with IBD disease state and endoscopic disease severity, thus providing insights into the underlying mechanisms of IBD pathogenesis as well as identifying potential biomarkers and therapies. Peripheral blood might constitute a suitable noninvasive diagnostic sample type, in which gene expression profiles might serve as indicators of ongoing mucosal inflammation, and thus guide personalized treatment decisions.