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Analysis of de novo donor-specific HLA-DPB1 antibodies in kidney transplantation
HLA ( IF 5.9 ) Pub Date : 2021-09-03 , DOI: 10.1111/tan.14422
Chen Tang 1 , Christian Unterrainer 1 , Annette Fink 1 , Sofia Cinca 1 , Andrea Ruhenstroth 1 , Sabine Scherer 1 , Christian Morath 2 , Martin Zeier 2 , Arianeb Mehrabi 3 , Caner Süsal 1 , Thuong Hien Tran 1
Affiliation  

HLA matching and avoidance of unacceptable mismatches are important aspects in the selection of donors for solid organ transplantation. The impact of HLA-DPB1 incompatibility on the outcomes of kidney transplantation is not fully understood. We investigated a potential effect of mismatching for HLA-DPB1 at allele, eplet, or Terasaki epitope (TerEp) level on the formation of de novo donor-specific antibodies (dnDSA) and also asked whether polymorphisms associated with HLA-DPB1 expression level may influence dnDSA induction. Furthermore, we analyzed the correlation between graft survival and HLA-DPB1 mismatches defined by different approaches. A cohort of 366 patients who received a kidney transplant at the Heidelberg University Hospital, Germany, with availability of pre- and post-transplant HLA antibody results by single antigen testing as well as of donor and recipient HLA-DPB1 high-resolution typing were analyzed retrospectively. Susceptibility to increased HLA-DPB1 expression was predicted by the linked dimorphism rs9277534 A/G of the HLA-DPB1 gene. Neither HLA-DPB1 mismatches at allele, eplet or TerEp level nor exposure to donor's high HLA-DPB1 expression were significantly associated with the risk of developing dnDSA against HLA-DPB1. However, HLA-DPB1 eplet and TerEp mismatches had a significant negative impact on graft survival (p < 0.001 and p = 0.003, respectively). Matching for HLA-DPB1 at epitope instead of allele level appears to have potential to improve graft survival in kidney transplantation.

中文翻译:

肾移植中新生供体特异性 HLA-DPB1 抗体的分析

HLA 匹配和避免不可接受的错配是实体器官移植供体选择的重要方面。HLA-DPB1 不相容对肾移植结果的影响尚不完全清楚。我们研究了 HLA-DPB1 在等位基因、eplet 或 Terasaki 表位 (TerEp) 水平上错配对新生供体特异性抗体 (dnDSA) 形成的潜在影响,并询问与 HLA-DPB1 表达水平相关的多态性是否可能影响dnDSA 诱导。此外,我们分析了不同方法定义的移植物存活和 HLA-DPB1 错配之间的相关性。一组 366 名在德国海德堡大学医院接受肾移植的患者,回顾性分析了通过单一抗原测试以及供体和受体 HLA-DPB1 高分辨率分型获得的移植前和移植后 HLA 抗体结果的可用性。HLA-DPB1 基因的连锁二态性 rs9277534 A/G 预测了对 HLA-DPB1 表达增加的易感性。HLA-DPB1 在等位基因、eplet 或 TerEp 水平上的错配或暴露于供体的高 HLA-DPB1 表达都与针对 HLA-DPB1 发生 dnDSA 的风险没有显着相关性。然而,HLA-DPB1 eplet 和 TerEp 错配对移植物存活有显着的负面影响。eplet 或 TerEp 水平或暴露于供体的高 HLA-DPB1 表达与发生针对 HLA-DPB1 的 dnDSA 的风险显着相关。然而,HLA-DPB1 eplet 和 TerEp 错配对移植物存活有显着的负面影响。eplet 或 TerEp 水平或暴露于供体的高 HLA-DPB1 表达与发生针对 HLA-DPB1 的 dnDSA 的风险显着相关。然而,HLA-DPB1 eplet 和 TerEp 错配对移植物存活有显着的负面影响。p  < 0.001 和p  = 0.003,分别)。在表位而不是等位基因水平匹配 HLA-DPB1 似乎有可能提高肾移植中的移植物存活率。
更新日期:2021-10-14
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