PURPOSE:
Extracellular matrix (ECM) deposition and remodelling in skin and lungs of systemic sclerosis (SSc) subjects lead to release of metabolites/biomarkers into circulation. We investigated if biomarkers of ECM degradation (biglycan and elastin) and macrophage activation (citrullinated vimentin) could identify diffuse SSc (dSSc) subjects from controls and the biomarkers discriminative power.

METHODS:
DSSc subjects (n = 40) fulfilling the 2013 EULAR/ACR classification criteria were divided in early (<2years of symptoms) and late (≥10years of symptoms). Early were subdivided into intermediate and rapid skin thickness progression rate (STPR). Twenty controls were included. Citrullinated and matrix metalloproteinase (MMP)-2/8-degraded vimentin (VICM), MMP-9/12-degraded biglycan (BGM) and MMP-7-degraded elastin (ELM-7) were assessed in serum. Analysis between groups was by Kruskal-Wallis and ROC AUC for discriminative power.

RESULTS:
VICM and BGM levels were increased in early compared to late dSSc (p< =0.023). VICM was increased in rapid and intermediate STPR compared to controls (p< =0.025). No differences in ELM-7 levels were observed. AUC of VICM was 0.71 for early versus late dSSc and BGM had an AUC of 0.79 for dSSc versus controls.

CONCLUSION:
This pilot study found differences in biomarker levels between early and late dSSc. This study offers new perspectives of ECM metabolites as potential biomarkers of dSSc.

KEYWORDS:
Biglycan; Systemic sclerosis; diagnostic potential of biomarkers; disease activity assessment; macrophage activation and secretion of vimentin; metabolites of the ECM