The expression of colonic keratins is elevated in IBD, reduced in microscopic colitis, and unchanged in IBS – a retrospective study

Abstract Background Keratins, a major subgroup of intermediate filament proteins, play a critical role in maintaining epithelial barrier and intracellular epithelial integrity. Studies have demonstrated possible links between inflammatory signaling and colonic keratins type II K8, and type I K18, K19 and K20, in animal models of colitis, and in patients with Inflammatory Bowel Disease (IBD). K7 is de novo expressed in patients with the IBD subtypes Ulcerative Colitis (UC) and Crohn’s Disease (CD). However, the histopathological roles of colonocyte keratins across IBD, microscopic colitis (MC), and Irritable Bowel Syndrome (IBS) remain poorly understood. Given the established utility as biomarkers in cancer diagnostics, we investigated whether keratin expression patterns could be used to distinguish inflammatory and functional colonic disorders. Methods Biobank samples from patients with IBD (n=27), MC (n=18), IBS (n=32) and healthy controls (n=31), were collected and immunohistochemically stained for K7, K8, K18, K19, and K20. Digital image analysis quantified staining intensities, which were correlated with histopathological severity scores and clinical parameters. Results Colonic keratin expression was significantly elevated in IBD, particularly in UC, while they were decreased in MC, and unaltered in IBS. Notably, K8 and K19 expression were strongly associated with areas of severe epithelial damage in IBD. Keratin expression was most pronounced in patients who had undergone colectomy due to treatment-resistant IBD. Discussion Keratin changes in IBD and MC but not in IBS highlight their importance in maintaining barrier homeostasis. Whether these changes are causes or consequences for these diseases will warrant further research.