Thammanichanond D, Parapiboon W, Mongkolsuk T, Worawichawong S, Tammakorn C, Kitpoka P
Histocompatibility and Immunogenetics Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Division of Nephrology, Department of Medicine, Maharat Nakhon Ratchasima Hospital, Thailand.
Transplant Proc. 2018 Oct;50(8):2548-2552. doi: 10.1016/j.transproceed.2018.02.190. Epub 2018 Mar 20.
The presence of isolated de novo anti-DP antibodies is uncommon, making it difficult to determine the impact of anti-DP antibodies on graft outcome. We describe a case of acute antibody-mediated rejection mediated by de novo donor-specific anti-HLA-DP antibodies. Furthermore, the generation of non-donor-specific anti-DP antibodies (NDSAs) detected in the patient's sera was investigated. An 18-year-old woman with pretransplant 0% panel-reactive antibody received kidney transplantation from a living donor. She experienced combined acute T-cell-mediated and antibody-mediated rejection at 15 months after transplantation. High resolution HLA typing of the donor and the patient revealed that they were mismatched at both DPB1 (DPB131:01) and DPA1 (DPA102:02) loci. The single antigen bead (SAB) testing of patient's sera revealed antibodies against donor's DPB131:01 and DPA102:02 alleles. Antibodies against several non-donor-specific DP antigens were also detected. No antibodies against other HLA class I and II antigens were detected. In order to explain the reactivity pattern of NDSAs, HLAMatchmaker program was used to identify immunizing eplets shared between donor alleles and reactive beads. The analysis showed 84DEAV, a DPB1 eplet, as a shared eplet found on DPB131:01 (mismatched donor allele) and on DPB1-reactive alleles in SAB assay. Additionally, 50RA, a DPA1 eplet, was identified as a shared eplet found on DPA102:02 (mismatched donor allele) and on DPA1-reactive alleles in SAB assay. This case highlights the clinical significance of HLA-DP antibodies. Furthermore, the generation of NDSA anti-DP antibodies by epitope sharing underscores the importance of HLA-DP epitope matching in kidney transplantation.
孤立的新生抗-DP抗体并不常见，因此难以确定抗-DP抗体对移植结果的影响。我们描述了一例由新生供体特异性抗HLA-DP抗体介导的急性抗体介导的排斥反应。此外，还对患者血清中检测到的非供体特异性抗-DP抗体（NDSA）的产生进行了研究。一名移植前群体反应性抗体为0%的18岁女性接受了活体供体的肾脏移植。她在移植后15个月经历了急性T细胞介导和抗体介导的联合排斥反应。对供体和患者进行的高分辨率HLA分型显示，他们在DPB1（DPB131:01）和DPA1（DPA102:02）位点均不匹配。患者血清的单抗原珠（SAB）检测显示存在针对供体DPB131:01和DPA102:02等位基因的抗体。还检测到了针对几种非供体特异性DP抗原的抗体。未检测到针对其他HLA I类和II类抗原的抗体。为了解释NDSA的反应模式，使用HLAMatchmaker程序来识别供体等位基因和反应性珠子之间共享的免疫表位。分析显示，84DEAV（一种DPB1表位）是在DPB131:01（不匹配的供体等位基因）和SAB检测中的DPB1反应性等位基因上发现的共享表位。此外，50RA（一种DPA1表位）被确定为在DPA102:02（不匹配的供体等位基因）和SAB检测中的DPA1反应性等位基因上发现的共享表位。该病例突出了HLA-DP抗体的临床意义。此外，通过表位共享产生NDSA抗-DP抗体强调了HLA-DP表位匹配在肾脏移植中的重要性。
