HLA 和 MICA：心脏移植中抗体介导排斥反应的靶标。
HLA and MICA: targets of antibody-mediated rejection in heart transplantation.
机构信息
Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
出版信息
Transplantation. 2011 May 27;91(10):1153-8. doi: 10.1097/TP.0b013e3182157d60.
BACKGROUND
The goal of this study was to determine whether antidonor antibodies directed against human leukocyte antigen (HLA) or endothelial cells (ECs) expressed antigens, including major histocompatibility complex class I chain-related antigens A (MICA) are associated with the diagnosis of antibody-mediated rejection (AMR) in heart transplant recipients.
METHODS
We studied posttransplant antidonor HLA antibodies in 168 heart allograft recipients transplanted from October 2001 to December 2005. Among them, there were 37 AMR+ patients and 131 age- and sex- matched AMR- controls. Sera were collected at the time of protocol biopsies and tested for the presence of HLA antibodies. Seventy-two of the 168 patients were genotyped for donor and recipient MICA alleles and were tested for the presence of anti-MICA antibodies. Thirty-one patients who never developed antibodies to HLA or MICA were further tested for anti-EC antibodies.
RESULTS AND CONCLUSIONS
Of 37 AMR+ patients, 22 (60%) developed donor-specific antibodies (DSA) to HLA compared with 6 of 131(4%) AMR- patients (P<0.0001). Of the remaining 15 AMR+ patients, 5 had anti-HLA antibodies that were not donor specific and 10 did not show any HLA antibodies. In the subgroup of 72 patients, all 19 AMR+ patients had clearly demonstrable antibodies reactive with donor HLA, MICA or with nondonor-derived ECs, with 30% of them showed antibodies directed to non-HLA antigens. The incidence of transplant coronary artery disease was significantly higher in patients who had DSA to HLA and MICA compared with patients without DSA.
背景
本研究旨在确定针对人类白细胞抗原（HLA）或内皮细胞（ECs）表达抗原的抗供体抗体（包括主要组织相容性复合物 I 类链相关抗原 A（MICA））是否与心脏移植受者抗体介导的排斥反应（AMR）的诊断有关。
方法
我们研究了 2001 年 10 月至 2005 年 12 月期间接受心脏移植的 168 名心脏移植受者的移植后抗供体 HLA 抗体。其中，37 例 AMR+患者和 131 例年龄和性别匹配的 AMR-对照组。在方案活检时采集血清，检测 HLA 抗体的存在。对 168 例患者中的 72 例进行了供体和受体 MICA 等位基因的基因分型，并检测了抗-MICA 抗体的存在。进一步对 31 例从未产生 HLA 或 MICA 抗体的患者进行了抗 EC 抗体检测。
结果和结论
在 37 例 AMR+患者中，22 例（60%）患者与 131 例 AMR-患者（6 例，4%）相比，对 HLA 产生了供体特异性抗体（DSA）（P<0.0001）。在其余 15 例 AMR+患者中，5 例患者的抗 HLA 抗体不是供体特异性的，10 例患者没有显示任何 HLA 抗体。在 72 例患者亚组中，所有 19 例 AMR+患者均有明确可检测的针对供体 HLA、MICA 或非供体来源的 ECs 的抗体，其中 30%的患者显示针对非 HLA 抗原的抗体。与无 DSA 的患者相比，对 HLA 和 MICA 有 DSA 的患者移植冠状动脉疾病的发生率明显更高。
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