Altered colonic keratin expression as a biomarker signature distinguishes IBD, microscopic colitis, and IBS – a retrospective study

Abstract Background Keratins are epithelial intermediate filament proteins that maintain tissue integrity, and their expression is altered in response to injury and inflammation. In addition to their established roles as biomarkers in epithelial cancers, emerging evidence suggests that keratin expression patterns are altered in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). Keratin 7 (K7) was recently demonstrated to be de novo expressed in the colon during IBD, but absent in patients with microscopic colitis (MC). Here we hypothesized that the expression patterns of colonic keratins K8, K18, K19, and K20, alongside K7, could be used to distinguish IBD, MC and the functional disorder, irritable bowel syndrome (IBS). Since these disorders present with overlapping symptoms, novel biomarkers are needed to support diagnostics development. Methods Biobank colon samples from two cohorts, Cohort I with IBD ( n = 26; (UC, n = 15; CD, n = 11)), MC ( n = 18), and controls ( n = 12) and Cohort II with IBS ( n = 32) and controls ( n = 19), were immunohistochemically stained for K7, K8, K18, K19, and K20. Digital image analysis was used to quantify staining intensities, which were compared between diseases, and correlated with histopathological severity scores and clinical parameters using ANOVA, Mann-Whitney test, and regression analyses. Results Colonic K8, K18 and K19 were increased in UC, and K18 in CD. In MC K8 and K19 were decreased, while in IBS K7, K8, K18-K20 were comparable to controls. In IBD, elevated K8 and K19 were associated with severe epithelial damage and correlated more strongly with features of chronic tissue injury than acute inflammation. In IBD patients, K7 levels correlated with K19. Conclusions Distinct colonic keratin patterns characterize IBD, MC, and IBS, with increased keratin expression in IBD, decreased expression in MC, and unchanged expression in IBS. These disease-specific patterns may have biomarker potential to support diagnosis of colon disorders, although further validation is required. The keratin alterations suggest a link to impaired barrier homeostasis, which is observed in IBD and MC. Whether these changes are among the causes or consequences for these diseases and what is the inducing mechanism warrants further research. Trial registration Clinical trial number: not applicable.