大动脉炎遗传发病机制  

The Genetic Pathogenesis of Takayasu Arteritis

作　　者：范泸韵(综述) 张慧敏(校审)[1] 蔡军(校审)[1] FAN Lu-vun ZHANG Hui-min CAI Jun(State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases. Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.)

机构地区：[1]北京协和医学院,中国医学科学院,国家心血管病中心,阜外医院,心血管病国家重点实验室,北京市100037

出　　处：《中国分子心脏病学杂志》2017年第4期2188-2192,共5页Molecular Cardiology of China

摘　　要：大动脉炎为一类机制不明的非特异性大血管炎,既往研究提示遗传因素参与其发病。人类白细胞抗原(HLA)-B~*52:01是唯一不同种族重复验证的大动脉炎易感基因,与主动脉瓣反流密切相关。HLA-B52抗原肽结合区的第67位氨基酸是大动脉炎特异性抗原表位,呈递内源性抗原后启动大动脉炎。HLA-B67、HLA-B/MICA基因是新发现的大动脉炎易感基因。大动脉炎中65-KD HSP及TNF-α分别通过HSE通路及NK-kB通路促使MICA表达上调,触发急性血管壁炎症。HLAⅡ类基因区的易感基因与种族背景相关,多以单倍型出现。HLA-DPB1~*09、HLA-DRB1~*07、HLA-DQB1~*06:01是中国人群大动脉炎易感基因。FCGR2A/FCGR3A基因可能参与的体液免疫加速大动脉炎进程。IL12B基因介导的Th1及Th17细胞通路是大动脉炎适应性免疫应答的重要机制,提示大动脉炎未来治疗方向。Objective This article is to systematically review the published data concerning the pathogenesis of TA in genetics and to indicate potential theraputic strategies. HLA-B＊52, HLA-B/MICA and HLA-B＊67 are susceptible alleles encoding HLA class I antigens. HLA-B＊52 is the only established risk genetic factor of TA repeatedly confirmed among populations and links with clinical manifestations especially aortic regurgitation（AR）. The 67 th amino acid might be the pathogenic component of HLA-B52 antigen in TA. The 65-KD mycobacterial heat-shock proteins（HSP） and serum TNF-aamong TA up-regulate MICA on vascular endothelial cells, mediated by heart shock response element（HSE）pathway and NK-κB pathway respectively. MICA initiates acute vascular inflammation independent of HLA class Ⅰ molecules. The HLA class Ⅱ susceptible alleles of TA are inherited in haplotypes and vary in races, of which HLA-DPB1＊09, HLA-DRB1＊07, HLA-DQB1＊06：01 are risk factors of Chinese TA patients. Humoral immunity correlating with FCGR2A/FCGR3 A alleles might participate in TA. IL12 B SNPs are repeatedly verified in correlation with TA. Inflammatory and cellular immunity axis mediated by IL-12 B genes seem to be cardinal mechanisms of TA and antagonists targeting them might be promising therapeutic methods.

关 键 词：系统综述 大动脉炎 发病机制 遗传 

分 类 号：R543.5[医药卫生—心血管疾病]