组织相容性Ⅰ类相关链A位点基因多态性在预判肾移植物排斥中的意义  

Role of major histocompatibility complex class Ⅰ chain-related gene A polymorphisms in allograft kidney rejection

作　　者：袁晓妮[1] 何军[1] 侯建全[2] 温端改[2] 鲍晓晶[1] 邱桥成[1] 王乾[2] 钟键[2] 李强[2] 

机构地区：[1]苏州大学附属第一医院江苏省血液研究所,苏州215006 [2]苏州大学附属第一医院泌尿外科,苏州215006

出　　处：《中华细胞与干细胞杂志（电子版）》2011年第2期14-19,共6页Chinese Journal of Cell and Stem Cell（Electronic Edition）

基　　金：国家自然科学基金(30872530);江苏省医学领军人才项目(LJ201138);江苏省医学重点学科(XK201151);苏州市科技基础设施建设计划项目(SZS201001;SZS0702)

摘　　要：目的研究组织相容性I类相关链A位点(MICA)基因多态性和抗MICA特异性抗体在肾移植排斥反应发生中的意义。方法采用免疫磁珠液相芯片技术对40例肾移植患者在移植术前和移植术后1个月、3个月、6个月、1年和2年动态检测抗MICA抗体的特异性和阳性分值的变化,同时采用SSOP方法分析16对肾移植供受者的MICA基因分型,并把MICA基因具有相同抗原表位的特征性分为G1组和G2组。结果在40例肾移植中尸体供肾35例,亲缘活体供肾5例。35例肾移植受者均带肾存活良好,其中33例接受动态随访。移植术前预存抗MICA抗体为12例,其中抗MICA抗体10例、抗HLA-I类+MICA抗体2例;4例分为MICA-G1组、6例分为MICA-G2组、2例共为MICA-G1和G2组。16对供受者MICA等位基因频率分布:在MICA-G1组中频率M﹡002最高,M﹡007次之;MICA-G2组中频率M﹡008最高,M﹡009和M﹡019次之。33例移植术后有4例新生抗MICA抗体,3例新生抗HLA抗体,均为抗供者特异性抗体和抗非供者特异性抗体。移植术前预存抗MICA抗体,在移植术后1～2年的动态随访中其特异性均未改变,而抗体的阳性分值呈现高低的变化。12例移植术前预存抗MICA抗体中的3例和抗体阴性1例移植术后发生急性排斥反应,临床表现为发热,尿量减少,肌酐和肾动脉阻力指数升高。33例动态随访资料显示:无论是MICA基因频率分布特点,还是抗MICA特异性抗体类型与排斥反应的关系,M﹡002、M﹡004、M﹡008、M﹡019和M﹡001基因型最常见,但未见MICA﹡012和MICA﹡006基因型。结论移植术前分析供受者的MICA基因多态性,受者的特异性抗体鉴定和特征性分组;移植术后动态监测抗MICA抗体的变化,是肾移植术后预防急性和慢性移植物排斥的重要靶分子。Objective To study the association of MHC class I chain related antigens A （MICA） polymorphisms and anti-MICA specific antibodies and renal allograft rejection. Mothods The specific anti-MICA antibodies of 40 patients were monitored using Flow PRATM beads from at transplantation and 1, 3, 6, 12 and 24 months post transplantation respectively. The MICA genotypes of 16 patients and donors were determined by PCR-SSOP. Two groups of public epitopes （MICA-G1 and MICA-G2） were characterized. Results Thirty-five out of the 40 renal allografis were from deceased donors and 5 from related livingdonors. Renal allograftfunction was good in 35 recipients. Twelve patients had pre-existing antibodies before transplantation in 40 patients （30.0 % ）： 10 patients with anti-MICA antibody and 2 patients with anti-MICA antibody and anti-HLA antibody. Four patients were found to have MICA-G1, 6 were found to have MICA-G2, and 2 have both MICA-G1 and MICA-G1. As to allele polymorphism distribution of 16 patients and donors, M ^＊ 002 had the highest frequency for MICA-G1 and M ^＊ 008 for MICA-G2. Four patients with anti-MICA antibodies and 3 patients with anti-HLA antibodies developed both donor specific and non-donor specific antibodies post transplantation. Antibody specificity did not change in the patients with anti-MICA specific antibodies before transplantation during the follow-up, but positive rate decreased. Among 12 recipients with pre-existing antibodies 3 developed acute rejection. For recipients without preexisting antibodies only one developed acute rejection. Fever, hypourocrinia and increased serum creatinine level and resistent index of kidney artery were most often seen during acute rejection. The frequency of M^＊ 002, M ^＊ 004, M^＊ 008, M ^＊ 019 and ^＊ 001 were highest while M^＊ 002 and M ^＊ 004 were not found. Conclusion MICA genotyping before-transplant, monitoring for MICA antibodies post-transplant, may be useful to establish target factors for acute rejection and chronic rejection

关 键 词：组织相容性Ⅰ类 基因多态性 抗体 肾移植 移植物排斥 

分 类 号：R699[医药卫生—泌尿科学]