Cysteine-rich protein 61 as a novel biomarker in systemic lupus erythematosus-associated pulmonary arterial hypertension

Objective This study aimed to evaluate the level of plasma Cysteine rich 61 (Cyr61) in systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) patients, and to explore the diagnostic and prognostic value of Cyr61 in SLE-PAH. Methods Plasma samples were obtained from 54 patients with definite SLE-PAH, 52 SLE-non-PAH patients and 54 healthy controls. Enzyme-linked immunosorbent assay was used to measure plasma Cyr61 concentration, and immunohistochemistry assay was adopted to identify Cyr61 protein expression in lung tissues of monocrotaline (MCT) induced PAH rats at different stages. Results Plasma Cyr61 concentration in SLE-PAH patients was significantly higher than matched SLE-non-PAH patients and healthy controls. The optimal cut-off value of Cyr61 in predicting the presence of PAH in entire SLE was 140.7 pg/ml. Further multivariate logistic regression analysis revealed that Cyr61 level >= 140.7 pg/ml was an independent risk factor for developing PAH in SLE patients. Kaplan-Meier analysis indicated that SLE-PAH patients with Cyr61 level >= 140.7 pg/ml had better survival than those with lower Cyr61 level (p=0.001 by Log-Rank test), and this was also confirmed by multivariate Cox regression analysis. In addition, Cyr61 protein expression was significantly higher in lung tissue of MCT induced PAH rats compared to control rats, and the expression was more significant in early-mid stage of PAH development than the late stage. Conclusion Plasma Cyr61 level was significantly higher in SLE-PAH patients. Elevated circulating Cyr61 is a useful biomarker for identifying PAH in SLE, and it may serve as a promising indicator of prognosis in SLE-PAH.