Serum biomarkers of collagen remodeling are associated with intestinal fibrosis and differentiate stenotic from luminal Crohn's disease patients: A Pre- and Post-Resection Longitudinal Study

BACKGROUND AND AIMS: Crohn's disease (CD) is characterized by progressive intestinal transmural damage, including fibrosis and strictures, which impair quality of life and require surgical intervention. No anti-stricture therapies are available, and no accurate biomarkers have been validated allowing prediction of strictures. Collagen fragments synthesis and remodeling show potential as markers of transmural disease activity. This study aimed to evaluate serum collagen markers for their accuracy in differentiating between stenosing and luminal CD and assessing their correlation with histopathology.

METHODS: Sixty-two patients undergoing resection for stricturing CD and 49 with luminal CD were prospectively included. ECM markers were quantified using ELISA, and histological assessments of fibrosis and inflammation were performed on full-thickness tissue samples. Clinical outcomes, biomarkers, and histology were analyzed over a 12-month follow-up.

RESULTS: ECM markers, including PRO-C6, PRO-C3, PRO-C5, C4M, and PRO-C4, distinguished stenosing from luminal CD with and the combination of PRO-C6, PRO-C3, and PRO-C5 achieved the highest discriminative power of (AUC 0.91). Significant changes in levels of the collagen biomarker were observed post-resection. Histological analysis revealed extensive intestinal fibrosis in the submucosa of the stenotic segments, which correlated with PRO-C6 levels. C4M and PRO-C4 positively correlated with neutrophils in lamina propria. CTX-III correlated negatively to the D'Haens score and neutrophils -and mononuclear cells in lamina propria and in epithelium.

CONCLUSION: Collagen markers distinguished stenosing from luminal CD, and they correlated to histological fibrosis and chronic inflammation promising for understanding ECM remodeling. This study highlights the need for extended follow-up to assess long-term stenosis-related outcomes.