• J Rheumatol · Dec 2002

    Increased circulating concentrations of the counteradhesive proteins SPARC and thrombospondin-1 in systemic sclerosis (scleroderma). Relationship to platelet and endothelial cell activation.

    • Richard F Macko, Allan C Gelber, Bradford A Young, Mark H Lowitt, Barbara White, Fredrick M Wigley, and Simeon E Goldblum.
    • Department of Neurology, VA Maryland Health Care Center, Baltimore 21201, USA.
    • J Rheumatol. 2002 Dec 1;29(12):2565-70.

    ObjectiveTo determine whether circulating concentrations of the counteradhesive proteins SPARC (secreted protein acidic and rich in cysteine) and thrombospondin-1 (TSP-1) are elevated in scleroderma (systemic sclerosis, SSc). The relationship of these counteradhesive proteins to measures of platelet and endothelial cell activation was examined.MethodsPlasma from 45 patients with SSc (26 limited form, 19 diffuse) and 22 age and sex matched controls was assayed for SPARC, TSP-1, beta-thromboglobulin (betaTG), and platelet factor 4 (PF4), 2 distinct platelet a-granule products, and soluble E-selectin, a marker of endothelial cell activation.ResultsThe mean (+/- SE) SPARC concentration was greater in patients with limited SSc (124.0 +/- 9.6 ng/ml) compared to controls (66.8 +/- 8.0 ng/ml) (p = 0.0005), whereas in patients with diffuse SSc (74.1 +/- 7.9 ng/ml) it was not. Elevated SPARC concentrations in the limited SSc group could not be ascribed to either platelet or endothelial cell activation. TSP-1 concentrations were also increased in SSc patients (n = 29) compared to controls (n = 11) (2.98 +/- 0.12 vs 2.4 +/- 0.21 log transformed ng/ml; p < 0.02). Unlike SPARC, TSP-1 concentrations correlated with both betaTG (r = 0.57, p = 0.0014) and PF4 (r = 0.41, p = 0.026) levels, indicating that increased TSP-1 could, in part, be explained through elevated platelet a-granule release in SSc patients. Plasma levels of betaTG, PF4, and E-selectin were each similarly elevated (p < 0.003) in patients with both limited and diffuse SSc compared to controls.ConclusionThat circulating SPARC and TSP-1 are elevated in patients with SSc raises the possibility that counteradhesive proteins, which regulate vascular organization and remodeling, might contribute to the pathogenesis of SSc vasculopathy.

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