Serological assessment of PRO-C16 (type XVI collagen formation) reflects intestinal fibrostenotic strictures in patients with crohn's disease

Background: Fibrostenotic stricturing disease affects 30-50% of patients with Crohn's disease (CD), leading to intestinal resection. Currently, there exists a great medical need to identify biomarkers related to fibrostenotic strictures for optimized patient management. Thus, we investigated PRO-C16 as a biomarker for intestinal fibrosis in patients with CD. Methods: Human serum from two independent cohorts of CD patients (cohort 1: n = 44, cohort 2: n = 52), healthy subjects (n = 37), and serum from a chronic rat dextran sodium sulfate (DSS) colitis model were included. The Montreal classification for CD disease behavior was applied for patient phenotyping. Results: PRO-C16 was elevated in patients with CD compared to healthy donors (P < 0.001), and in CD patients with fibrostenotic strictures in both cohorts. Furthermore, PRO-C16 was able to separate CD patients with strictures(B2) from CD patients without strictures (B1 and B3) (Cohort 1 [P < 0.01, AUC:0.75], and Cohort 2 [P < 0.05, AUC:0.71). In the chronic DSS rat colitis model, PRO-C16 was elevated after the second and fourth cycles of DSS, reflecting collagen deposition in that model. Conclusion: The biomarker PRO-C16 was associated with a stricturing disease phenotype, indicating that PRO-C16 may be a potential marker of intestinal fibrosis in CD, with the potential to aid in the clinical development of novel stromal-immune therapeutic agents.