Circulating microvesicles as novel biomarkers for pulmonary arterial hypertension in patients with systemic lupus erythematosus

Abstract

Pulmonary arterial hypertension (PAH) is a serious complication of systemic lupus erythematosus (SLE) with increased mortality. A prothrombotic state may contribute to pathogenesis of SLE-PAH. Microvesicles (MVs) are known to be associated with thrombosis. Here, we investigated circulating MVs and their associations with SLE-PAH. Eighteen SLE-PAH patients, 36 SLE-non-PAH patients, and 36 healthy controls (HCs) were enrolled. Flow cytometry was used to analyze circulating MVs from leukocytes (LMVs), red blood cells (RMVs), platelets (PMVs), endothelial cells (EMVs), and Annexin V+ MVs with phosphatidylserine (PS) exposure. Plasma levels of all MV subgroups were elevated in SLE patients with or without PAH compared to HCs. Furthermore, plasma Annexin V+ MVs, LMVs, PMVs, RMVs, EMVs, and Annexin V+ RMVs were significantly elevated in SLE-PAH patients compared to SLE-non-PAH patients. Additionally, PAH patients with moderate/high SLE showed a significant increase in LMVs, PMVs, RMVs, Annexin V+ MVs, and Annexin V+ RMVs compared to SLE-non-PAH patients. However, PAH patients with inactive/mild SLE only exhibited elevations in Annexin V+ MVs, RMVs, and Annexin V+ RMVs. In the SLE-PAH patients, EMVs were positively correlated with pulmonary arterial systolic pressure, while PMVs and EMVs were positively correlated with right ventricular diameter. Moreover, the receiver operating characteristic curve indicated that Annexin V+ MVs, LMVs, PMVs, RMVs, EMVs and Annexin V+ RMVs can predict the presence of PAH in SLE patients. Importantly, multivariate logistic regression analysis showed that circulating levels of LMVs or RMVs, anti-nRNP antibody, and serositis were independent risk factors for PAH in SLE patients. Finally, our findings reveal that specific subgroups of circulating MVs contribute to the hypercoagulation state and the severity of SLE-PAH. Higher plasma levels of LMVs or RMVs may serve as biomarkers for SLE-PAH.