Serum REG3α as a Biomarker for Clinical and Endoscopic Activity in Ulcerative Colitis

Introduction Current biomarkers, including serum C-reactive protein (CRP) and fecal calprotectin, have limitations in monitoring disease activity of ulcerative colitis (UC). Regenerating islet-derived protein 3𝛼 (REG3𝛼), which is constitutively produced by Paneth cells, is a bactericidal C-type protein against Gram-positive bacteria. Preliminary studies suggest that REG3α may serve as a promising novel blood-based biomarker for assessing disease activity in patients with UC. Methods A total of 128 patients with UC were prospectively enrolled. Blood samples were obtained on the same day as endoscopy. Serological markers including REG3𝛼, CRP, albumin, and serum calprotectin were measured. The clinical and endoscopic activity were assessed using the total Mayo score (remission, mild, or moderate-to-severe) and the Mayo endoscopic subscore (MES), respectively. Results Serum levels of REG3𝛼, CRP, albumin, and calprotectin were significantly correlated with clinical activity (Mayo score ≥ 6) (Spearman’s r= 0.362, P < 0.001; r= 0.429, P < 0.001; r= −0.312, P < 0.001; and r= 0.253, P = 0.004, respectively). Serum levels of REG3𝛼, CRP, and albumin were also significantly correlated with endoscopic activity (MES ≥ 2) (r= 0.362, P < 0.001; r= 0.420, P < 0.001; and r= −0.240, P = 0.006, respectively), whereas serum calprotectin was not (r = 0.147, P = 0.098). The combination of serum REG3𝛼and CRP predicted clinical and endoscopic activity with the AUC values of 0.847 and 0.783, respectively, both of which surpassed the performance of the individual biomarkers. Among 19 patients who underwent serial follow-up of REG3α levels, a significant decrease was observed during periods of clinical improvement ( P = 0.005). Conclusion REG3α is a novel serological biomarker that reflects both clinical and endoscopic activity in UC. When combined with CRP, it provides superior predictive performance compared with individual biomarkers. Serial monitoring further indicates that REG3α may serve as a valuable tool for assessing disease activity and monitoring treatment response in patients with UC.