P087 Biomarkers of elastin degradation differentiate between clinically inactive and active disease in ulcerative colitis patients

Abstract

Abstract Background In ulcerative colitis (UC), the state of chronic inflammation results in increased matrix metalloprotease (MMP) and serine protease activity, which effectively leads to a higher degree of intestinal tissue remodelling, including components of the extracellular matrix (ECM). One of these components is elastin a matrix protein of the interstitial matrix in the lamina propria and submucosa, providing tissue resilience and elasticity. As such, we investigated whether elastin degradation in UC patients was associated with disease activity and severity, potentially enabling patient differentiation based on elastin degradation. Methods Twenty-nine UC patients and 29 healthy donors were included in the study. Disease activity was determined according to the partial Mayo score (pMayo >1) and the Mayo Endoscopic Score (MES). Disease severity and extension was assessed using the Montreal classification. Disease severity was additionally assessed using the Trulove and Witt’s (TW) clinical score. The biomarkers of elastin degradation included: MMP-7 (ELM-7) cathepsin-G (EL-CG) and proteinase-3 (ELP-3), measured in serum by ELISA. One-way ANOVA (Kruskal–Wallis) correcting for the false discovery rate were applied for the statistical analysis. Results TW: ELP-3 levels in moderate-to-severe UC patients were significantly elevated in comparison with HD (p < 0.001). Partial Mayo: EL-CG levels in patients with active UC were significantly elevated in comparison with HD (p < 0.01), and UC patients in remission (p < 0.01). ELP-3 levels were likewise significantly elevated in active UC patients compared with HD (p < 0.001), and UC patients in remission (p < 0.01). Montreal classification: ELM-7 was significantly elevated in active UC compared with HD (p < 0.05), and UC patients in remission (p < 0.05). EL-CG were also significantly elevated in active UC compared with HD (p < 0.05), and UC patients in remission (p < 0.05). ELP-3 was significantly elevated in active UC compared with HD (p < 0.01). According to the MES score, ELP-3 levels in moderate-to-severe UC patients were significantly elevated in comparison to HD (p < 0.01). Conclusion The data presented in this study demonstrate an association between biomarkers of proteolytic elastin degradation and disease activity in UC patients especially the protease-3-derived biomarker, ELP-3, showed significant association with active UC in all the clinical scoring systems as well as the MES score. Utilising these minimally invasive elastin degradation biomarkers could serve as surrogate markers for monitoring of disease activity and potentially aid the differentiation of patients with an active disease from patients in remission or with a lower disease activity for UC.