Serum REG3α Emerges as Promising Blood-Based Biomarker for Ulcerative Colitis Disease Monitoring
Key Insights
Serum REG3α (search) demonstrated significant correlation with both clinical (ρ=0.362, P<0.001) and endoscopic (ρ=0.362, P<0.001) disease activity in a prospective study of 128 ulcerative colitis (search) patients.
The combination of REG3α (search) and CRP predicted clinical and endoscopic activity with AUC values of 0.847 and 0.783, respectively, outperforming either biomarker alone.
Serial monitoring in 19 patients showed significant REG3α (search) decreases during clinical improvement (P=0.005), though findings remain preliminary due to small sample size.
A prospective study published in Scientific Reports has identified serum regenerating islet-derived protein 3α (REG3α (search)) as a promising blood-based biomarker for monitoring disease activity in patients with ulcerative colitis (search) (UC). The findings suggest that REG3α, particularly when interpreted alongside C-reactive protein (search) (CRP), may offer a useful adjunctive option for disease assessment when stool-based testing is less feasible.
The study, led by Kim SJ and colleagues, enrolled 128 patients with UC and collected blood samples on the same day as endoscopy. Investigators measured serum REG3α (search), CRP, albumin, and serum calprotectin (search), then assessed clinical and endoscopic activity using the total Mayo score and the Mayo endoscopic subscore (MES), respectively.
Correlation with Clinical and Endoscopic Activity
Serum REG3α (search), CRP, albumin, and serum calprotectin (search) all demonstrated significant correlations with clinical activity, defined as a Mayo score of at least 6. REG3α showed a Spearman's correlation coefficient of ρ=0.362 (P<0.001), while CRP reached ρ=0.429 (P<0.001), albumin showed an inverse correlation at ρ=−0.312 (P<0.001), and serum calprotectin registered ρ=0.253 (P=0.004).
For endoscopic activity, defined as an MES of at least 2, serum REG3α (search), CRP, and albumin remained significantly associated with disease severity. REG3α correlated at ρ=0.362 (P<0.001), CRP at ρ=0.420 (P<0.001), and albumin at ρ=−0.240 (P=0.006). Notably, serum calprotectin (search) did not reach statistical significance for endoscopic activity (ρ=0.147, P=0.098).
Combined Biomarker Approach Enhances Predictive Performance
The investigators evaluated the discriminatory performance of combining serum REG3α (search) with CRP. The combined model predicted clinical activity with an area under the curve (AUC) of 0.847 and endoscopic activity with an AUC of 0.783, demonstrating improved performance compared with either biomarker alone within this study cohort.
REG3α (search) is constitutively produced by Paneth cells and functions as a bactericidal C-type protein against Gram-positive bacteria. Current biomarkers, including serum CRP and fecal calprotectin (search), have recognized limitations in monitoring UC disease activity, creating an unmet need for reliable blood-based alternatives.
Preliminary Serial Monitoring Data
Among 19 patients who underwent serial follow-up of REG3α (search) levels, a significant decrease was observed during periods of clinical improvement (P=0.005). However, the authors emphasized that these serial monitoring findings should be interpreted as preliminary given the limited sample size.
Limitations and Future Directions
The investigators cautioned that the combined REG3α (search)–CRP model should be considered exploratory. The study authors concluded that further validation in larger, independent cohorts—including direct comparison with fecal calprotectin (search)—is required before broader clinical application can be considered. The serum-based approach may prove particularly valuable as an adjunctive option when stool-based testing presents logistical challenges.