Proteomics highlights common and distinct pathophysiological processes associated with ileal and colonic ulcers in Crohn's disease.

BACKGROUND AND AIMS: Based on genetics and natural history, Crohn's disease can be separated in two entities, an ileal and a colonic disease. Protein based-approaches are needed to elucidate whether such subphenotypes are related to distinct pathophysiological processes. METHODS: The proteome of ulcer edge was compared to the one of paired control tissue (n=32 biopsies) by differential proteomics in the ileum and the colon of Crohn's disease patients (n=16). The results were analysed though a hypothesis-driven (based on literature) and a hypothesis-free approach (pathway enrichment analysis). To confirm one of the key pathway highlighted by proteomics, two proteins were also studied by immunochemistry in tissue biopsies. RESULTS: In the ileum and the colon, 4428 and 5204 proteins, respectively, were identified and quantified. Ileal and colonic ulcer edge differed by a distinct distribution of proteins of epithelial-mesenchymal transition, neutrophil degranulation and ribosome. Ileal and colonic ulcer edge were similarly characterised by an increase of the proteins implicated in the pathway of protein processing in endoplasmic reticulum and a decrease of mitochondrial proteins. Immunochemistry confirmed the presence of endoplasmic reticulum stress in the mucosa of ileal and colonic ulcer edge. CONCLUSION: This study provides protein-based evidences showing partly distinct pathophysiological processes associated to ileal and colonic ulcer edge in Crohn's disease patients. This could constitute a first step toward the development of gut segment-specific diagnostic markers and therapeutics.