【摘要】 目的特发性扩张型心肌病(idiopathic dilated cardiomyopathy,IDC)的发病机制与T细胞免疫应答密切相关。细胞毒性T淋巴细胞相关抗原24(cytotoxic Tlymphocyte antigen-4,CTLA-4)主要在已激活的T细胞上表达,通过与CD28竞争结合B7,抑制T细胞过度激活,维持免疫系统内环境稳定。CTLA-4基因3′非翻译区(AT)n微卫星多态性影响CTLA-4功能。本研究旨在探讨外周血单个核细胞(PBMC)CTLA-4表达状况及3′非翻译区(AT)n微卫星基因多态性与IDC的相关性。方法分别用原位杂交、免疫组化、序列特异性引物PCR等方法检测38例无血缘关系的北方汉族IDC患者以及50例正常对照者的CTLA-4 mRNA、蛋白质表达、CTLA24基因外显子3′末端非翻译区(AT)n重复序列多态性,并对PCR扩增产物进行序列分析。结果IDC组与对照组相比,PBMC经金黄色葡萄球菌肠毒素B刺激后CTLA-4 mRNA、蛋白质表达强度显著减弱,且无一定规律;3′末端非翻译区共发现18种CTLA24等位基因,与对照组比较,106bp等位基因频率在IDC患者中显著增高[22.22%vs1%,P=0.0002,OR=23.56,95%可信区间(CI):9.65～83.74]。结论IDC患者CTLA-4基因转录和表达缺陷,该缺陷与CTLA-4基因3′末端非翻译区(AT)n重复序列多态性存在关联。更多还原

【Abstract】 Objective To investigate an association between CTLA-4 gene 3′ untranslated region microsatellite polymorphisms and IDC and to explore the immunogenetic pathogenesis of IDC. Methods Genetically unrelated Chinese Han patients 38 with IDC and healthy controls 50 were studied. Expression of CTLA-4 mRNA and antigen was detected by in situ hybridization and immunohistochemistry. The (AT) n repeat sequence in the 3′ untranslated region of exon 4 was amplified by allele-specific PCR. The amplified products were electrophorosised by 12% polyacrylamid gel and then examined by silver staining. Results Expression of both mRNA and antigen of CTLA-4 was significantly but unregularly weaker on PBMC induced by staphytococcal enterotoxin B(SEB) in patients than that in normal controls. Eighteen alleles of CTLA-4 microsatellite were found in Chinese patients and healthy individuals. Long allele, 106 bp was apparently increased in patients with IDC as compared with healthy controls (22.22% vs 1%, P=0.0002, OR=23.56, 95% CI: 9.65-83.74). Conclusion Defective translation and expression of CTLA-4 take place in patients with IDC, it is possibly related to the CTLA-4 gene microsatellite polymorphism.更多还原