Potential biomarkers for detecting pulmonary arterial hypertension in patients with systemic sclerosis

Abstract

Pulmonary arterial hypertension (PAH) is the major complication of systemic sclerosis (SSc) and the main cause of morbi-mortality. It is important to find predictors for this vascular problem. The objective of this study was to determine the serum levels of different biomarkers in patients with SSc and secondary PAH and to compare them with those of healthy control subjects to define their potential role as predictors of PAH. Cross-section study in which 20 patients with SSc were included. PAH was diagnosed by echocardiogram. The optical densities of endoglin (Eng), endothelin-1 (ET-1), platelet-derived growth factor (PDGF), tumoral necrosis factor alpha (TNF-alpha), Transforming growth factor beta 2 (TGF-beta2) and Interleukin 8 (IL-8) were measured in 20 patients with SSc and 20 healthy controls matched by sex. The differences found between the group of patients with PAH and the control group were (mean or median and range): ET-1 (0.20; 0.10-0.35 vs. 0.16; 0.10-0.24; P = 0.0276), IL-8 (195.7; 45.5-504 vs. 118.9; 23-299.5; P = 0.0364), TNF-alpha (0.70; 0.50-0.96 vs. 0.48; 0.38-0.65; P = 1 x 10(-8)) and Eng (0.95; 0.57-1.72 vs. 0.75; 0.57-0.89; P = 0.0028). A correlation was found between the progression of the disease and the development of Raynaud's phenomenon (Rho: 0.67 and P = 0.0011), ET-1 and Eng (Rho: 0.53 and P = 0.0196), and between IL-8 and Eng (Rho: 0.68 and P = 0.0019). In conclusions, the elevation of the serum levels of Eng and ET-1 could represent a useful tool as PAH biomarkers. Nevertheless, the diagnostic value of these markers needs to be determined by prospective studies.

Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea

“…TGF-b levels have previously been measured in serum samples of patients with SSc and morphoea with discordant results. 31,[33][34][35][36][37][38] Clinical heterogeneity and a lack of a standardized assessment of clinical variables limits the interpretation of these earlier studies. 39 However, in agreement with our data, a recent study using a high-sensitivity ELISA detected reduced levels of active TGF-b in patients with SSc.…”

Biomarkers in the Management of Scleroderma: An Update

“…Given its high feasibility, if confirmed in a larger cohort, it could be a very useful instrument to stratify SSc patients based on the risk of development of cardiac and pulmonary artery involvement. Additional potential biomarkers of PAH were recently investigated in SSc patients [66]. In this crosssectional study, undertaken among 20 SSc patients with an echocardiographic diagnosis of secondary PAH, endothelin-1, interleukin-8, tumor necrosis factor-α, and endoglin (Eng) levels were found to be significantly elevated in SSc patients compared with healthy controls, with correlations between endothelin-1 and Eng and between interleukin-8 and Eng also reported.…”

Role of Endoglin in Fibrosis and Scleroderma

“…Soluble endoglin levels, which are known to be involved in the pathogenesis of pre-eclampsia, were reported to be increased in fibrosis patients, SSc patients and SSc patients with pulmonary arterial hypertension (Clemente et al, 2006; Coral-Alvarado et al, 2009; Fujimoto et al, 2006). Animal models of fibrosis also show a significant increase in endoglin expression compared to control conditions (Docherty et al, 2006; Prieto et al, 2005a; Prieto et al, 2005b; Rodriguez-Pena et al, 2001; Rodriguez-Pena et al, 2002).…”