Laser-microdissected transcriptomics of colonic epithelium and lamina propria in ulcerative colitis patients before anti-TNF therapy

To identify compartment-specific molecular signatures associated with treatment outcome, we used laser capture microdissection (LCM) to isolate colonic epithelium and lamina propria separately from paired inflamed and uninflamed mucosal biopsies. Biopsies were collected by colonoscopy before anti-TNF initiation from biologic-naive UC patients with left-sided colitis or pancolitis (Montreal E2/E3) and active disease (endoscopic Mayo subscore 2/3); patients were later classified as responders or non-responders based on endoscopic outcome at 6 months.

RNA sequencing of the microdissected epithelial and lamina propria compartments, combined with baseline serum cytokine profiling, showed that the strongest baseline differences between non-responders and responders were found in the uninflamed lamina propria, where a co-expression network enriched for humoral immune genes and elevated cell-cycle genes was more highly expressed in non-responders; cellular deconvolution and tissue staining localized this signature to IgA plasma cells.