P136 Blood-based biomarkers of type III collagen remodeling as surrogate markers of endoscopic disease activity in patients with Ulcerative Colitis

Abstract

Abstract Background The chronic inflammation of Ulcerative Colitis (UC) causes excessive extracellular matrix (ECM) remodeling, resulting in clinical complications. Currently, endoscopic evaluation remains the gold standard method for determining disease activity. However, due to its invasiveness and accompanying patient discomfort, novel methods are wanted. Focusing on type III collagen, a major component of the intestinal ECM, we sought to investigate three blood-based neoepitope biomarkers of type III collagen formation, degradation, and fibrosis resolution as surrogate markers of disease activity. Methods Fifty-one patients with UC were scored endoscopically at weeks 0 (W0) and 24 (W24), according to the total Mayo score (TMS) and the UC Endoscopic Index of Severity (UCEIS). Three biomarkers of type III collagen remodeling, PRO-C3 (formation), C3M (MMP-9 degradation), and CTX-III (fibrosis resolution), were measured in the sera of patients and evaluated against the disease activity scores. Patients were grouped based on their disease activity score, and the biomarkers were evaluated by one-way ANOVA, correcting for multiple comparisons using Tukey (parametric data) or Dunn’s test (nonparametric). Results Grouping patients according to the TMS at W0, patients with severe disease had elevated serum C3M compared to patients with mild or moderate disease (p<0.05 and <0.01) (Figure 1A). Based on the UCEIS, patients with a severe disease presented with reduced CTX-III than moderate disease activity (p<0.05) (Figure 1C). While not statistically significant, a numerical trend of elevated C3M levels with increasing endoscopic disease activity was observed at W24 (Figure 1B). No statistically significant results were achieved evaluating C3M according to the UCEIS score, CTX-III according to the TMS or PRO-C3 according to the TMS and UCEIS score (Data not shown). Conclusion The serum levels of C3M were elevated in patients with UC at W0 when scoring their endoscopic disease activity using the TMS. At W24, a similar trend of elevated C3M with increasing disease activity could be observed. Using the UCEIS score, the CTX-III biomarker reflecting type III collagen resolution was reduced in patients with severe endoscopic disease. The data suggest an elevation of MMP-9 catalyzed type III collagen degradation with disease severity and reduced type III collagen resolution. The PRO-C3 biomarker provided no statistical value in the current study.