Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis

Abstract

Objective. Vascular injury and endothelial cell (EC) activation are pathogenic hallmarks of systemic sclerosis (SSc; scleroderma). Human CD90 is highly expressed on activated ECs and can be shed from the cell surface. This study was conducted to examine whether soluble CD90 (sCD90) is elevated in the sera of patients with SSc and linked to pulmonary involvement and in particular, pulmonary arterial hypertension (PAH). Methods. sCD90 serum concentrations were assessed in 76 patients with SSc and related to clinical data, lung function, 6-minute walk distance, echocardiography, bronchoalveolar lavage fluid, and laboratory parameters. Thirty-one healthy volunteers and 29 patients with idiopathic retroperitoneal fibrosis (IRF) served as controls. Results. sCD90 serum concentrations were elevated in patients with SSc compared to healthy volunteers (P ‫؍‬ 0.001) and patients with IRF (P ‫؍‬ 0.01). SSc patients with pulmonary fibrosis (P ‫؍‬ 0.006) and patients with PAH (P < 0.001) had increased sCD90 serum concentrations compared to patients without the respective pulmonary manifestation of SSc. sCD90 levels correlated with diffusing capacity for carbon monoxide (n ‫؍‬ 65; r ‫؍‬ ؊0.348, P ‫؍‬ 0.005) and systolic pulmonary artery pressure (n ‫؍‬ 53; r ‫؍‬ 0.469, P < 0.001). Receiver operating characteristic curve testing determined an optimal cutoff value of >626 ng/ml with a sensitivity of 68% and a specificity of 83% for PAH (area under the curve 0.773, 95% confidence interval 0.648 -0.898; P < 0.001). Conclusion. sCD90 concentrations were increased in the sera of SSc patients, particularly in patients with vascular involvement of the lungs. These data suggest that sCD90 should be further evaluated as a marker for diagnosis of PAH in SSc.

Subspecificities of anticentromeric protein A antibodies identify systemic sclerosis patients at higher risk of pulmonary vascular disease

“…The relationship between age and increased sPAP was previously reported by Kollert et al [31] in a cohort of 76 patients with SSc. These investigators found that age and sCD90, the marker that was the object of their study, were independent variables predicting PAH.…”

“…PAH can also be predicted by endothelial cell proteins (e.g., CD90), [31] markers of natural immunity activation (e.g., CXCL4 and pentraxin 3), [37,38] or N-terminal pro-brain natriuretic peptide, [39] with a diagnosis of pulmonary hypertension being made in these studies with echocardiography, [31] right heart catheterization, [37,38] or both. [39] Although the mechanisms underlying the association of these markers and increased sPAP can be deduced, given the demonstrated role of endothelial cell activation or natural immunity in the early vasculopathy events leading to PAH, [40] the mechanisms underlying the ability of anti-pc4.2 and anti-pc14.1 antibody levels to predict an increased sPAP remain to be determined.…”

Thy‐1: more than a marker for mesenchymal stromal cells

“…Due to its glycosyl-phosphatidylinositol anchor, Thy-1 is sensitive to cleavage by phosphatidylinositol-specific PLC. The shedding of Thy-1 from the cell surface as described for several adhesion molecules (e.g., intercellular adhesion molecule 1) and its presence as a soluble molecule in serum have also been reported (11)(12)(13)(14)(15).…”

“…In addition, increased concentrations of soluble (s)Thy-1 were found in sera of systemic sclerosis patients, particularly in those with vascular involvement of the lungs. This suggests the use of sThy-1 in serum as a marker for the diagnosis of pulmonary arterial hypertension in systemic sclerosis (12).…”

Thy1 (CD90) controls adipogenesis by regulating activity of the Src family kinase, Fyn

“…However, membrane cleavage of Thy1 affects its localization and functional properties, and it is thus unclear if cleaved Thy1 could control adipogenesis (41). Recently elevated levels of a soluble form of Thy1 have been associated with scleroderma, a fibrotic disease (42). It may be interesting to determine if soluble Thy1 levels are decreased in obesity and thus serve as a novel biomarker.…”