316 Chapter 10 Abstract Background Increased collagen remodeling is a key pathophysiological component underlying intestinal stricture and fistula development in Crohn’s disease (CD). Aims In this study, we aimed to investigate associations between serological biomarkers of collagen turnover and disease behavior according to the Montreal classification in patients with CD. Methods Serological biomarkers of type III/IV collagen formation (PRO-C3, PRO-C4) and matrix metalloproteinase (MMP) or granzyme-B (GrzB)-mediated type I, III, IV, andVI collagen degradation (C1M, C3M, C4M, C4G, C6Ma3) were measured using neo-epitope protein fingerprint assays in 101 patients with CD (Montreal B1: n=37; B2: n=27; B3: n=37) and 96 controls. Patients were followed-up until their last outpatient visit to monitor stricturing/penetrating disease progression and recurrence and the occurrence of surgical interventions. Results C1M, C3M, and C4M were significantly reduced in patients with stricturing disease (Montreal B2) and accurately differentiated them from patients with either non-stricturing, non-penetrating (B1) or penetrating (B3) disease (all P<0.001, multivariable analysis). Similarly, the type IV collagen formation/degradation (PRO-C4/C4M) ratio demonstrated high discriminative capacity (B1/B2: AUC=0.90; B1/B3: AUC=0.87, both P<0.001, multivariable analysis). Prospectively, higher baseline levels of C1M and C4G were associated with an increased risk of penetrating disease progression (C4G: hazard ratio [HR]1.71[1.05-2.81], P<0.05). Conclusions Elevated degradation of type I, III, and IV collagen and excessive (relative) formation of type IV collagen strongly associates with stricturing CD. Type I and IV collagen fragments show predictive potential for the risk of penetrating disease progression. These biomarkers may become valuable tools for detection and prediction of stricturing and penetrating CD. Keywords Crohn’s disease; Montreal classification; biomarkers; collagen; fibrosis.
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