Serum biomarkers of collagen turnover as potential diagnostic tools in diffuse systemic sclerosis: A cross-sectional study

BACKGROUND: Systemic sclerosis (SSc) is characterized by excessive fibrosis throughout the body. This leads to the release of extracellular matrix (ECM) fragments into circulation, where they may be quantified as biomarkers. The objectives were to investigate levels of ECM turnover biomarkers and the diagnostic power of these. METHODS: Diffuse SSc patients (n = 40) fulfilling the ACR/EULAR 2013 classification criteria and asymptomatic controls were included. Patients were divided into early (<2 years of symptoms; n = 20) and late (>10 years of symptoms; n = 20) diffuse SSc. Biomarkers of type I (C1M), III (C3A, C3M), IV (C4M), V (C5M) and VI (C6M) collagen degradation and type I (PRO-C1), II (PRO-C2), III (PRO-C3), IV (PRO-C4), V (PRO-C5) and VI (PRO-C6) collagen formation were measured in serum. Repeated measures ANOVA was used to test for differences in biomarker levels and the area under the receiver operating characteristic curve (AUC) was used to investigate the ability of the biomarkers to separate groups. RESULTS: In early diffuse SSc, formation biomarkers of type III, IV, V and VI collagen were significantly increased compared to asymptomatic controls (p<0.0001). Moreover, in early diffuse SSc formation biomarkers of type III, V and VI collagen were significantly increased compared to late diffuse SSc (p = 0.0006, 0.003 and 0.004, respectively). Type I (p<0.0001), III (C3M: p = 0.001, and C3A: p = 0.02), IV (p<0.0001) and VI (p<0.0001) collagen degradation biomarkers significantly increased in early diffuse SSc compared to controls. C4M, C6M, PRO-C4, PRO-C5 and PRO-C6 had an AUC of >0.85 when assessing asymptomatic controls vs. diffuse SSc. Biomarkers of type VI collagen (PRO-C6 and C6M) turnover had the best separation with an AUC’s of >0.90. CONCLUSION: Formation biomarkers of ECM turnover were shown to be significantly different between asymptomatic controls and diffuse SSc. This pilot study suggest that serological biomarkers of the ECM turnover is potentially applicable in SSc.