P336 Exploring Extracellular Matrix Markers in Ulcerative Colitis: Degradation and Formation Insights

Abstract

Abstract Background The gold standard for assessing disease activity in ulcerative colitis (UC) is endoscopy, which is uncomfortable for the patient, and only evaluates the superficial layers of the colon. Intestinal extracellular matrix (ECM) remodeling is highly dynamic during disease activity and blood spillover of ECM components might reflect transmural disease burden. The aim of this study was to evaluate baseline serum markers of ECM formation (PRO-C11, PRO-C22, and PRO-C7) and degradation (C7M) to assess disease activity and treatment response in UC. Methods Forty-nine UC patients with active disease and 50 healthy controls (HC) were included. All underwent endoscopy and blood sampling at inclusion. UC patients additionally had fecal calprotectin (FCP) measured at baseline and had treatment adjusted at the discretion of the attending physician. Subsequent follow up of UC patients included clinical activity score, FCP, and blood samples at 3 and 6 months as well as an endoscopy at 6 months. Ulcerative Colitis Endoscopic Index of Severity (UCEIS), total Mayo score (TMS), and disease extent (E1-E3) was registered. Response was defined as a reduction from severe to moderate or mild disease based on TMS. If no follow-up endoscopy was performed (n=9), partial Mayo was used. Spearman’s correlation and one-way-ANOVA with Turkey correlation and correction for multiple testing were applied for statistical analysis. Results All markers of ECM degradation and formation were elevated in patients with severely active UC measured by both UCEIS and TMS compared to HC (adjusted p<0.0001 for each marker). CM7 and PRO-C22 differentiated moderate from severe UC by TMS (p<0.0001) and UCEIS (p<0.05) (Figure 1A-B). Baseline C7M, PRO-C7, and PRO-C11 correlated with CRP (Spearman’s: r=0.82, p<0.0001; r=-0.45, p=0.0012; and r=-0.33, p=0.032, respectively). None of the markers correlated with FCP. Elevated C7M, PRO-C7, and PRO-C11 levels for E3 could differentiate E3 from E1 (Difference ng/ml: 3.89 (SE of diff: 1.47), 13.15 (4.55), 10.08 (4.09), respectively, all p<0.05) (Figure 1C-E). Remission was achieved in 18/49 patients at 6 months. Both C7M and PRO-22 exhibited acceptable discriminative capabilities at baseline for 6-month TMS between remission and non-remission (AUC 0.72 (95% CI 0.58-0.87) p=0.01 and AUC 0.68 (95% CI 0.53-0.83) p=0.04, respectively) (Figure 1F-G). Conclusion This study demonstrates that ECM markers correlate with disease activity, disease extent, and predict future disease outcome in UC. ECM markers hold great promise as they provide a 'window' into transmural tissue remodeling and inflammatory and fibrotic burden, warranting further investigation.