REG3A: A Potential Fecal Biomarker for Ulcerative Colitis

Regenerating islet-derived protein 3-alpha (REG3A), a member of the regenerating islet-derived protein (Reg) family, belongs to the C-type lectin class of antimicrobial peptides (AMPs). It has been recognized as a critical component of intestinal mucosal barrier damage and repair. In a prospective cohort (82 ulcerative colitis [UC] patients, 20 controls), UC patients were stratified by clinical partial Mayo Score (pMS) and endoscopic activity. Fecal REG3A levels were measured across distinct patient cohorts, and diagnostic performance was evaluated and compared against fecal calprotectin (FC) and a combined model using receiver operating characteristic (ROC) analysis. REG3A expression was also evaluated in intestinal biopsies via immunohistochemistry. Fecal REG3A levels increased stepwise with UC clinical severity (p  < 0.001), peaking in the severe activity group. A combined model of REG3A and FC outperformed either biomarker alone in differentiating disease activity, achieving the highest area under the curves (AUCs) for distinguishing remission from mild activity and mild from moderate activity. Immunohistochemistry confirmed REG3A expression in active UC colonic tissues. Our results indicate that fecal REG3A serves as a promising biomarker for assessing disease activity in UC. Its combination with FC enhances the accuracy of predicting clinical severity in UC.