HLA Laboratory, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
Hum Immunol. 2020 Jul;81(7):330-336. doi: 10.1016/j.humimm.2020.04.003. Epub 2020 Apr 17.
The development of donor specific antibody is associated with graft rejection and increased mortality in solid organ transplant recipients. The majority of de novo donor specific antibodies (dnDSA) are against HLA-DQ antigens, but it has not been investigated if this is caused by more mismatches in the HLA-DQ locus between the recipient and donor. Here we examined the impact of HLA mismatches in eight HLA loci on the development of dnDSA and on rejection in a large cohort of heart transplant recipients. We evaluated HLA mismatches at the antigen level, the eplet level using HLAMatchmaker, and the epitope level using the PIRCHE algorithm. We found that the majority of dnDSA were against HLA-DQ antigens, and the number of dnDSA per mismatch is highest for HLA-DQ compared to other HLA loci. Furthermore, mismatches of HLA-DQ at the epitope level were associated with antibody-mediated rejection. Our results suggest that HLA mismatches at the HLA-DQ locus are more immunogenic than mismatches at other HLA loci to stimulate the development of dnDSA and to cause graft rejection.
供体特异性抗体的产生与实体器官移植受者的移植物排斥和死亡率增加有关。大多数新出现的供体特异性抗体（dnDSA）针对 HLA-DQ 抗原，但尚未研究这是否是由于受者和供者之间 HLA-DQ 基因座中更多的错配引起的。在这里，我们在一个大型心脏移植受者队列中研究了八个 HLA 基因座中 HLA 错配对 dnDSA 形成和排斥的影响。我们评估了抗原水平、HLAMatchmaker 中的 eplet 水平和 PIRCHE 算法中的表位水平的 HLA 错配。我们发现大多数 dnDSA 针对 HLA-DQ 抗原，与其他 HLA 基因座相比，每个错配的 dnDSA 数量在 HLA-DQ 中最高。此外，HLA-DQ 表位水平的错配与抗体介导的排斥反应有关。我们的结果表明，HLA-DQ 基因座上的 HLA 错配比其他 HLA 基因座上的错配更具免疫原性，从而刺激 dnDSA 的产生并导致移植物排斥。
