AB0647 ASSOCIATION OF VASCULAR BIOMARKERS WITH SYSTEMIC SCLEROSIS CLINICAL FEATURES AND NAILFOLD VIDEOCAPILLAROSCOPY ALTERATIONS-CROSS SECTIONAL STUDY

Abstract

Background: The most reliable markers reflecting endothelial activation and injury in Systemic sclerosis (SSc), are intercellular adhesion molecule (ICAM1), vascular cell adhesion molecule (VCAM1), E selectin (Es) and P selectin (Ps) (1). Objective(s): To assess concentrations of these vascular biomarkers in SSc patients (pts) in comparison to healthy controls (HC) and in relation to disease manifestations. Method(s): Patients who fulfilled the 2013 ACR/EULAR SSc classification criteria and have never been treated with endothelin receptor antagonist, phosphodiesterase 5 inhibitors or prostanoids were eligibile. Exclusion criteria were overlap syndromes, other autoimmune and cardiovascular diseases, diabetes mellitus, thrombosis, pregnancy, active infection or neoplastic diseases. Our study included 53 SSc pts [34 limited (lcSSc) and 19 diffuse cutaneous SSc (dcSSc)] and 31 age- A nd sex matched HC. Serum concentration of ICAM1, VCAM1, Es and Ps were measured using a commercial ELISA kit (Quantikine; R&D Systems), expressed as ng/mL. Clinical evaluation of patients was obtained, including nailfold videocapillaroscopy (NVC). Disease activity was assessed by the revised EUSTAR activity index. Statistical analysis was done in R. Student's t-test or ANOVA, otherwise Mann-Whitney U or Kruskal-Wallis tests were used. Pearson's or Spearman's correlation were done depends on nature of data. ICAM1 cut off value were assessed with ROC analysis. Association were performed with univariate logistic regression for NVC alterations and multivariate for Anti-TopoI/Scl70 antibodies (aTSa). Result(s): Concentration of all markers were elevated in SSc pts compared to HC (ICAM1 p<0.001, VCAM1 p<0.001, Es p<0.05, Ps p>0.05). Different disease subsets exhibited higher values of ICAM1 and VCAM1 respect to HC (lSSc p <0.05, dSSc p<0.001). Concentration of ICAM1 was higher in dcSSc compared to lcSSc (p<0.05). ICAM1 level were independently associated with positive aTSa (OR 1.2, 95% CI 1.02-1.35, p<0.001), with distinguishing cut off value of 34.94 (Sn 0.90%, Sp 0.60%, AUC 0.85). ICAM 1 was positively correlated with the erythrocyte sedimentation rate (r 0.3, p<0.05) especially within disease duration > 3 years group (r 0.4, p<0.05). Higher levels of ICAM1 was found in diffusing capacity of the lungs for carbon monoxide<70% (p<0.05), modified Rodnan skin score >14 (p<0.05) and active disease (p<0.05) group. Calcinosis group had decreased level of Es (p<0.05) and increased Ps (p<0.05). Es was lower in group with acroosteolysis (p<0.05). Trends towards increasing markers concentration from early to late NVC pattern were observed for all biomarkers except Es which showed the highest concentration in active group, but without significant differences (p>0.05). Few megacapilaries were associated with ICAM1 (OR 1.2, 95% CI 1.06-1.34, p<0.05) and Ps (OR 1.2, 95% CI 1.08-1.39, p<0.05), while presence of bushy capillaries were associated with ICAM1 (OR 1.3, 95% CI 1.06-1.36, p<0.05) level. Conclusion(s): Our results support the role of vascular biomarkers in SSc pathogenesis. Besides anti-TopoI/Scl70 antibodies, ICAM-1 could be used as an additional marker of dSSc. Elevation of ICAM1 and Ps concentration might be associated with late NVC alterations.