SAT0200 Serum Biomarkers of Collagen Turnover in Early and Late Diffuse Systemic Sclerosis

Background Systemic sclerosis (SSc) is characterized by vascular damage and excessive collagen deposition in the skin and internal organs. The excessive collagen deposition results from accelerated turnover, both formation and degradation, contributing to release of extracellular matrix (ECM) fragments to the circulation, where they may be quantified as biomarkers. Skin is rich in type I and III collagen, while type IV, V and VI collagen are present in a lesser amount. Thus, the turnover of these collagens is potentially altered in SSc. Objectives The objective was to investigate the level of collagen (type, I, III, IV, V and VI) turnover in early and late stage diffuse SSc patients compared to healthy controls (HC). Methods Diffuse SSc patients (n=40) were included together with HC (n=20). Twenty patients were early diffuse ( 10 years of disease with stable skin for at least six months), all without progressive lung disease. Biomarkers of type I, III, IV, V and VI collagen formation (P1NP, Pro-C3, P4NP7S, Pro-C5 and Pro-C6, respectively) and type I, III, IV and VI collagen degradation (C1M, C3M, C3A, C4M2 and C6M, respectively) were assessed in serum. Statistical differences between the groups were tested by Kruskal-Wallis test with Dunn9s multiple comparisons test. The potential discrimination capacity of these biomarkers were analysed by receiver operating characteristics (ROC) area under the curve (AUC) on HC, SSc, early and late diffuse SSc versus each other. Results In early diffuse SSc Pro-C3, P4NP7S, Pro-C5 and Pro-C6 (p The degradation biomarkers were significantly increased in early SSc compared to HC (C1M, C4M2 and C6M: p The best predictive value was found for Pro-C6 and C6M with AUC values of 0.92 and 0.93 for HC vs. SSc, 0.94 and 0.99 for HC vs. early diffuse, and 0.91 and 0.87 for HC vs. late diffuse, respectively. Pro-C6 had an AUC of 0.88 for early vs. late diffuse. In addition, C4M2, Pro-C3, P4NP7S and Pro C5 all had AUC values of more than 0.90 when assessing HC vs. early diffuse. Conclusions This pilot study showed that collagen turnover appears to be significantly different between HC and SSc, as well as between early and late stage diffuse patients. The discriminatory power of these biomarkers was high, especially C6M and Pro-C6. These data suggest that serological assessment of ECM turnover could be relevant in SSc, and offers an area of investigation of the pathogenesis. Disclosure of Interest P. Juhl: None declared, R. Domsic: None declared, A.-C. Bay-Jensen: None declared, M. Karsdal: None declared, A. Siebuhr: None declared, N. Franchimont Shareholder of: Biogen, Employee of: Biogen, J. Chavez Shareholder of: Biogen, Employee of: Biogen