Session Information
Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud’s – Pathogenesis, Animal Models and Genetics
Session Type: Abstract Submissions (ACR)
Background/Purpose: To assess whether nailfold videocapillaroscopy (NVC) changes are associated with peripheral blood or serum levels of angiogenic biomarkers in systemic sclerosis (SSc).
Methods: Endothelial markers were assessed in a cohort of 60 SSc patients consecutively recruited. Circulating endothelial progenitor cells (EPCs) were quantified in peripheral blood by flow cytometry after cell sorting, as previously described (1). Serum levels of vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), soluble vascular adhesion molecule (sVCAM), endothelin-1 (ET1), angiopoietin-2, endoglin, endostatin and Tie-2, were measured by quantitative sandwich enzyme-linked immunosorbent assay (ELISA) technique (Quantikine kits, R&D systems). Capillaroscopy was performed on 8 fingers, at 200x magnification, by a single examiner (JA), on two consecutive fields extending over 1 mm, in the middle of the nailfold. Images were analysed anonymously by four investigators (VS, AS, CP and MC), blinded for the clinical and serum status of SSc patients and classified as early, active and late pattern (2).
Results: The mean ± standard deviation (SD) age of the 60 patients (46 women) was 56±13 year old and the mean ± SD disease duration was 9±8 years at baseline. Thirty-six patients had the diffuse cutaneous subset, and 24 the limited. Fourteen patients had an early, 22 an active, and 24 a late NVC pattern. By univariate analysis focused on biomarkers, patients with late NVC pattern exhibited significantly lower EPC levels and higher VEGF serum levels than patients with early and active patterns (p=0.001 and p=0.01, respectively). Endothelin serum levels were significantly higher in the active pattern compared to early and late patterns (p=0.02). In multivariate multiple regression analysis, lower EPC and higher VEGF levels were independently associated with the late capillaroscopic pattern (p=0.007 and p=0.0008 respectively). In an alternate model including these 2 biomarkers and SSc-related disease characteristics, lower EPC counts, higher VEGF levels, and a modified Rodnan skin (mRSS) score >14, were independently associated, in multiple regression analysis, with the late capillaroscopic pattern (p=0.02, p=0.0001 and p=0.0003, respectively).
Conclusion: Our data revealed decreased EPC counts in patients with the late capillaroscopic pattern, suggesting that deficient vasculogenesis may contribute to the severe loss of capillaries observed in this pattern. VEGF upregulation in the late pattern may appear as a compensatory mechanism to stimulate this deficient vasculogenesis and could be implicated in the altered vessel morphology observed in this pattern. In addition, a mRSS>14 was independently associated with the late NVC pattern, highlighting from the clinical side the fibrotic component of this pattern. Further studies are now needed to determine the predictive value of capillaroscopy, in combination with these biomarkers, for the development of the vascular complications of SSc.
References: (1) Avouac et al, Ann Rheum Dis 2008, (2) Cutolo M et al. J Rheumatol. 2000
Disclosure:
J. Avouac,
None;
M. Vallucci,
None;
V. Smith,
None;
B. Ruiz,
None;
A. Sulli,
None;
C. Pizzorni,
None;
G. Chiocchia,
None;
M. Cutolo,
None;
Y. Allanore,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/low-circulating-endothelial-progenitor-cell-levels-and-high-vegf-serum-levels-are-associated-with-the-late-nailfold-capillaroscopic-pattern-in-systemic-sclerosis/