Impact of donor mismatches at individual HLA-A, -B, -C, -DR, and -DQ loci on the development of HLA-specific antibodies in patients listed for repeat renal transplantation
Impact of donor mismatches at individual HLA-A, -B, -C, -DR, and -DQ loci on the development of HLA-specific antibodies in patients listed for repeat renal transplantation
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DOI：
10.1038/ki.2014.106
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发表时间：
2014-11-01
影响因子：
19.6
通讯作者：
Bradley, J. Andrew
中科院分区：
文献类型：
--
作者：
Kosmoliaptsis, Vasilios;Gjorgjimajkoska, Olivera;Bradley, J. Andrew
我们分析了每个 HLA 基因座的供体错配与列入重复移植的患者中 HLA 基因座特异性抗体的产生之间的关系。使用单抗原珠对 131 名肾移植受者进行 HLA 抗体筛查，这些受者在第一次移植失败后返回移植等待名单。针对每个 HLA 基因座，确定了 HLA 错配的数量以及针对 10,000 名连续死亡器官捐献者的抗体反应性的计算反应频率。等待重复移植的患者中有三分之二是过敏的（计算出的反应频率超过 15%），一半是高度过敏的（计算出的反应频率为 85% 或更高）。重新列入重复移植名单后，抗体水平达到峰值，与移植肾切除术无关，并且与等待名单上的时间长度（比值比 8.4）以及维持双重免疫抑制（比值比 0.2）相关。致敏与供体 HLA 不匹配数量的增加独立相关（比值比 1.4）。所有不匹配的 HLA 位点均有助于 HLA 位点特异性抗体的形成（HLA-A：优势比 3.2，HLA-B：优势比 3.4，HLA-C：优势比 2.5，HLA-DRB1：优势比 3.5，HLA-DRB3/4/5：优势比 3.9，HLA-DQ：优势比 3.0（均显着））。因此，随着评估的所有 HLA 基因座的错配数量的增加，第一次肾移植失败后异体过敏的风险逐渐增加。重新列入名单的患者维持双重免疫抑制与致敏风险降低相关。
We have analyzed the relationship between donor mismatches at each HLA locus and development of HLA locus-specific antibodies in patients listed for repeat transplantation. HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The number of HLA mismatches and the calculated reaction frequency of antibody reactivity against 10,000 consecutive deceased organ donors were determined for each HLA locus. Two-thirds of patients awaiting repeat transplantation were sensitized (calculated reaction frequency over 15%) and half were highly sensitized (calculated reaction frequency of 85% and greater). Antibody levels peaked after re-listing for repeat transplantation, were independent of graft nephrectomy and were associated with length of time on the waiting list (odds ratio 8.4) and with maintenance on dual immunosuppression (odds ratio 0.2). Sensitization was independently associated with increasing number of donor HLA mismatches (odds ratio 1.4). All mismatched HLA loci contributed to the development of HLA locus-specific antibodies (HLA-A: odds ratio 3.2, HLA-B: odds ratio 3.4, HLA-C: odds ratio 2.5, HLA-DRB1: odds ratio 3.5, HLA-DRB3/4/5: odds ratio 3.9, and HLA-DQ: odds ratio 3.0 (all significant)). Thus, the risk of allosensitization following failure of a first renal transplant increases incrementally with the number of mismatches at all HLA loci assessed. Maintenance of re-listed patients on dual immunosuppression was associated with a reduced risk of sensitization.