P127 Type I collagen degradation fragments (C1M) and human neutrophil elastase-derived fragments of calprotectin (CPa9-HNE) reflect biochemical and endoscopic disease activity in patients with Inflammatory Bowel Disease

Abstract Background Crohn’s disease (CD) and ulcerative colitis (UC) are characterized by intestinal inflammation and increased extracellular matrix (ECM) remodeling, which are key pathophysiological mechanisms in patients with IBD and highly related to mucosal damage. Alterations in intestinal ECM turnover as well as macrophage and neutrophil activity may be reflected by secreted products that are released into the systemic circulation. In this study, we aimed to investigate associations between serum biomarkers of neutrophil activity (serum calprotectin) and collagen degradation (mucosal damage), and disease activity in patients with IBD. Methods Serological biomarkers of collagen formation (PRO-C3, PRO-C4, PRO-C6), matrix metalloproteinase (MMP)-mediated collagen degradation (C1M, C3M, C4M, C4G, C6Ma3) and intestinal inflammation (VICM [macrophage activity], human neutrophil elastase-derived fragment of calprotectin (CPa9-HNE [serum calprotectin, neutrophil activity]) were measured using Protein FingerPrint assay (PFA) technology in 100 patients with IBD (CD: n=44; UC: n=56). Biochemical disease activity was assessed using C-reactive protein (CRP) levels and available faecal calprotectin (FCal) levels. Endoscopic disease activity was determined using the Simple Endoscopic Score for CD (SES-CD) and Mayo endoscopic subscore for UC. Results C1M strongly associated with elevated CRP levels (defined as >5mg/L, P<0.001) in patients with IBD and significantly associated with faecal calprotectin levels in patients with UC (Spearman’s ρ=0.75, P<0.001). In patients with CD, C1M reasonably discriminated between patients with mild and moderate-to-severe endoscopic disease activity (AUC=0.73, P=0.01), whereas this discrimination was more subtle in patients with UC (AUC=0.68, P=0.08). CPa9-HNE levels were significantly increased in patients with elevated CRP levels (P=0.002 for both CD and UC) and associated best with faecal calprotectin levels in patients with CD compared with UC (CD: ρ=0.43, P=0.06; UC: ρ=0.20, P=0.45). Finally, CPa9-HNE levels were able to discriminate between mild and moderate-to-severe endoscopic disease activity in patients with CD (AUC=0.75, P<0.01). Conclusion C1M and CPa9-HNE levels associate with biochemical (CRP, FCal) and endoscopic disease activity in patients IBD, where C1M demonstrated higher accuracy in UC and CPa9-HNE appeared to be more useful in CD in this cohort. Therefore, C1M and CPa9-HNE could serve as surrogate biomarkers for the assessment of disease activity in patients with UC and CD, respectively. Our results should be validated in additional prospective, larger patient cohorts to corroborate these findings.