抗内皮素A型受体抗体在狼疮相关肺动脉高压中的致病性  

Anti-endothelin receptor type A autoantibody in lupus associated pulmonary arterial hypertension

作　　者：赵江峰[1] 郭丽[1] 陈怡[1] 潘曙明[1] 叶霜[1] 

机构地区：[1]上海交通大学附属医学院附属仁济医院风湿科,200001

出　　处：《中华风湿病学杂志》2015年第3期156-159,I0001,共5页Chinese Journal of Rheumatology

基　　金：上海市科委资助项目（13DZ1941000-003）

摘　　要：目的探讨抗内皮素A型受体抗体（ENRA．Ab）作为新的生物标记物在SLE相关肺动脉高压（SEE，PAH）中的临床意义，揭示其在SLE—PAH中可能的免疫致病性。方法筛选合成内皮素A型受体的表位肽段，建立基于抗原肽的ELISA方法检测SLE—PAH组和对照组血清中的ENRA-Ab；分析该抗体与SLE．PAH的临床相关性。多抗ENRA—AbIgG于体外不同条件下刺激血管平滑肌细胞（SMC）、内皮细胞，检测其对SMC增殖、内皮通透性及PAH主要致病因子表达的影响。利用亚剂量野百合碱构建大鼠模型探讨ENRA-AbIgG的体内效应，从右心室肥厚指数和病理学表现评估该抗体对PAH进展的影响。采用t检验、方差分析的Tukey-Kramer检验与Marson相关分析进行统计学分析。结果41％（35／85）的SLE—PAH患者血清中存在ENRA-Ab，明显高于SLE非PAH组16％（13／80）和健康对照组（0／60）；在SLE-PAH中，该抗体水平与心脏彩色多普勒超声估测肺动脉收缩压（PASP）有显著相关性（r=0．392，P=0．002）。ENRA—Ab可促进SMC增殖，破坏内皮屏障，上调PAH主要致病因子表达，且可被内皮素受体拮抗剂所阻断。在体内，ENRA-Ab可加重大鼠右心室肥厚，促进肺血管重构。结论ENRA-Ab是SLE-PAH一个新的生物标记物，其可能介导SLE．PAH的免疫致病。Objective To investigate autoantibody against endothelin receptor type A （ENRA-Ab） in patients with systemic lupus erythematosus associated pulmonary arterial hypertension （SLE-PAH）. The possibility of autoantibody-mediated pathogenesis in the development of SLE-PAH has also been explored. Methods ENRA-Ab in the serum of SLE-PAH and controls were detected by using a human ETRA epitope peptide-based ELISA. The clinical relevance of ENRA-Ab in SLE-PAH was analyzed. Proliferation of vascular smooth muscle cells （SMCs） and permeability of endothelial cells in vitro under the stimulation of polyclonal ENRA-Ab IgG were assessed. The expressions of PAH-related markers, i.e., 5-HTI＇, PDGFR-b, VEGF-A and PDGF-B were measured by qPCR. The effect of ENRA-Ab in vivo was also determined in a suboptimal- dose monocrotaline-induced model with the assessment of right ventricle hypertrophy index and pathology parameters. Independent t-test, Tukey-Kramer test of variance analysis and Pearson~ s correlation analysis were used for statistical analysis. Results ENRA-Abs was presented in a higher occurrence in SLE-PAH （35/85, 41%） compared with controls （0/60; 0, 13/80, 16%）. There was a significant correlation between ENRA-Ab and echocardiograph estimated pulmonary arterial systolic pressure （r=0.392, P=-0.002） in SLE-PAH. ENRA-Ab could promote SMCs proliferation, disrupt endothelial barrier and up-regulate PAH-related markers expression, which could be blocked in the presence of ETR antagonist. ENRA-Ab aggravated right ventricle hypertrophy and vascular remodeling in vivo. Conclusion ENRA-Ab is a new biomarker, in SLE-PAH, which may mediate PAH development in SLE.

关 键 词：受体 内皮素A 自身抗体 红斑狼疮 系统性 高血压 肺性 

分 类 号：R593.24[医药卫生—内科学] R544.1[医药卫生—临床医学]