抗内皮素受体A抗体在狼疮相关肺动脉高压中的作用及机制研究

Pulmonary Arterial Hypertension (PAH) secondary to Systemic Lupus Eythematosus(SLE) is the typical target organ damage mediated by autoimmunity.We have identified a novel autoantibody against endothelin-1 receptor type A (anti-ETRA) which was presented in more than 40 percent of SLE-PAH. An anti-ETRA ELISA assay has been established to evaluate its potential clinical value as a biomarker for SLE-PAH in large scale of population. In Preliminary experiments, we found that ETRA-Ab play a role in the lesion of PAH, and then hypothesized that anti-ETRA may mediate the development of SLE-PAH. On the basis, we try to explore the specific pathogenic mechanism of anti-ETRA in SLE-PAH. With a better understanding of this severe clinical problem and its possible autoantibody mediated mechanism, this project could provide useful biomarker and promise targeted-therapy to improve the prognosis of SLE-PAH.

系统性红斑狼疮（SLE）合并肺动脉高压（PAH）是其具有代表性的免疫介导的靶器官损伤。本课题组前期首先发现了在超过40%的SLE-PAH患者血清中存在抗内皮素受体A的自身抗体（anti-ETRA），并就此建立了anti-ETRA的Elisa检测方法，通过扩大样本验证，有望最终明确该潜在生物标记物的临床应用价值。初步发现该抗体在PAH的发生、发展中有一定作用，进而首次提出了anti-ETRA抗体在SLE-PAH中的免疫致病假说，在此基础上试图探讨该抗体在SLE-PAH中的具体致病机制。本项目针对SLE-PAH这一临床严重问题，发展生物标记物、揭示其可能的自身抗体介导的免疫致病机理，有望发掘更为有效的靶向治疗策略，以期最终改善部分SLE-PAH的预后。