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 significantly 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 significantly elevated after the second and fourth cycle of DSS, reflective of collagen deposition in that model Conclusion The biomarker PRO-C16 was significantly associated with stricturing disease phenotype, indicating that PRO-C16 may be employed as a marker of intestinal fibrosis in CD, with the potential to aid in the clinical development of novel stromal-immune therapeutic agents.