Background Systemic sclerosis (SSc) is a severe connective tissue disease characterized by vascular and fibrotic changes in the skin and various internal organs. Pathogenesis of SSc includes early-onset vasculopathy with endothelial cell activation, microvascular injury and impaired angiogenesis.
Objectives We aimed to determine the association of several biological molecules reflecting endothelial cell activation or dysfunction: E- selectin (E-sel), inter-cellular adhesion molecule 1 (ICAM-1), endothelin 1 (ET-1), von Willebrand factor (vWF) and interleukin 6 (IL-6), with distinct capillaroscopic SSc patterns and with more severe disease.
Methods Forty consecutive SSc patients attending our EUSTAR SSc clinic, aged [median (IQR)] 52 (18) years, male gender 4/40 (10%), diffuse cutaneous subset (dcSSc) 14/40 (35%) were enrolled in this study. Extensive clinical and nailfold capillaroscopy (NFC) pattern assessment, as well as quantification of serum E-sel, ICAM-1, ET-1, vWF, IL-6 and C-reactive protein (CRP) were performed on all patients. Associations between vascular biomarkers and disease characteristics were evaluated by Mann-Whitney U-test and Spearman correlations.
Results NFC “late” pattern was found in 21 patients, while 6 had “early” and 13 had “active” NFC pattern. All 5 vascular biomarkers correlated with each other good to moderately, with r indices varying between 0.660 and 0.332, the only exception being ET-1 which did not correlate with E-sel. Good correlations (r 0.465 to 0.727) were also found between all 5 biomarkers and CRP. Patients with severe vasculopathy, as reflected by the NFC “late” pattern, had higher levels of IL-6 (median 12.06 vs. 3.08 pg/mL, p=0.001), ET-1 (median 2.06 vs 1.59 pg/mL, p=0.029), vWF (median 3284 vs 2730 IU/mL, p=0.013) and E-sel (median 52.6 vs. 42.3 ng/mL, p>0.05), compared to patients with NFC “early” or “active” patterns. There was a significant, negative correlation between lung transfer for carbon monoxide (DLCO) and E-sel, ICAM-1 (both p<0.001) and vWF (p=0.013). ET-1 was higher in patients with more severe disease (dcSSc, patients positive for anti-topoisomerase antibodies and patients with a history of digital ulcers – all p<0.05).
Conclusions Serum biomarkers reflecting endothelial cell activation and/or dysfunction are elevated in patients with more severe SSc-associated vasculopathy and correlate with serum CRP. Together with NFC data they might be used for assessing vasculopathy severity in SSc and identifying patients who would benefit from more aggressive vasoactive treatment.
Acknowledgements This work was performed as part of the project “Development of a computer-based nailfold videocapillaroscopy (NVC) system for longitudinal evaluation of patients with systemic sclerosis” (QUANTICAP), financed by the UEFISCDI PN-II-PT-PCCA-2013–4-1589 grant.
Disclosure of Interest None declared