P0282 Fibroblast activation protein (FAP)-cleaved type III Collagen [C3F] is a potential marker for intestinal fibrosis in patients with Crohn’s Disease
T Tsapanou Katranara, A Poulsen, M Sorokina Alexdóttir, L Buhl Riis, M Pehrsson, J Rasmussen, I Gögenur, J Burisch, M A Karsdal, A C Bay-Jensen, J B Seidelin, J H MortensenAbstract
Background
Crohn ‘s disease (CD) is characterized by chronic inflammation in the gut, where severe complications such as fibrotic strictures require surgical resection. Stricture development involves excessive extracellular matrix (ECM) deposition due to continuous activation of intestinal myofibroblasts, that further contribute to intestinal fibrogenesis. Emerging data suggests that stricture-related intestinal myofibroblasts overexpress a serine protease called fibroblast activation protein (FAP). Furthermore, type III collagen deposition is increased during fibrosis in all layers of the intestinal tract, and studies have shown elevated collagen degradation in serum from patients with CD. The present study aimed at evaluating the potential of FAP-cleaved type III collagen [C3F] as a serum marker for intestinal fibrosis in CD.
Methods
The cohort consisted of 49 patients with luminal CD and 62 patients with stenotic CD. Clinical assessment was conducted for all patients at baseline and 12 months post study initiation. For the luminal phenotype, endoscopy was performed at both time points. For the stenotic group, radiographical assessment was done prior to surgery and endoscopy was performed at 12 months. C3F was measured in serum at all timepoints for baseline, post-operative day (POD), 1, 3, 6 and 12 months. To compare C3F levels at baseline for luminal vs stenotic phenotype, Mann-Whitney U-test was conducted. For the stenotic group, mixed-effect analysis, with a Dunnett’s multiple comparison, was conducted to compare C3F levels for baseline vs POD and Spearman’s rank correlation was applied.
Results
C3F baseline levels were significantly higher in patients with stenotic CD compared to luminal CD (Figure 1). In the stenotic group, C3F was significantly increased in patients at POD compared to baseline (Figure 1). Furthermore, C3F showed a positive correlation with C-reactive protein (CRP) (ρ=0.28, p=0.006) and a significant negative correlation with disease duration (ρ= -0.257, p=0.048) for patients with the stenotic CD phenotype (Table 1).
Conclusion
C3F was elevated in patients with stenotic CD, with even higher levels after the surgical resection. The data suggests that C3F reflects fibroblast activity during fibrostenosis and tissue remodeling following surgery. The positive correlation with CRP supports the association with inflammation leading to collagen deposition and fibrosis. Interestingly, C3F shows negative correlation with disease duration suggesting that C3F could reflect fibrosis at early stages of stenotic CD. These findings highlight the potential use of C3F as a novel biomarker for intestinal fibrosis in CD.