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分析肾移植中供体特异性 HLA-DPB1 抗体的形成。

Analysis of de novo donor-specific HLA-DPB1 antibodies in kidney transplantation.

机构信息

Transplantation Immunology, Institute of Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Division of Nephrology, Heidelberg University Hospital, Heidelberg, Germany.

出版信息

HLA. 2021 Nov;98(5):423-430. doi: 10.1111/tan.14422. Epub 2021 Sep 14.

Abstract

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.

摘要

HLA 匹配和避免不可接受的错配是实体器官移植中选择供体的重要方面。HLA-DPB1 不匹配对肾移植结局的影响尚未完全阐明。我们研究了 HLA-DPB1 等位基因、eplet 或 Terasaki 表位(TerEp)水平错配对新产生的供体特异性抗体(dnDSA)形成的潜在影响,还探讨了与 HLA-DPB1 表达水平相关的多态性是否可能影响 dnDSA 的诱导。此外,我们还分析了不同方法定义的 HLA-DPB1 错配与移植物存活率之间的相关性。回顾性分析了德国海德堡大学医院的 366 例接受肾移植的患者,这些患者具有通过单抗原检测获得的移植前和移植后 HLA 抗体结果,以及供体和受体 HLA-DPB1 高分辨率分型。HLA-DPB1 基因的连锁二态性 rs9277534 A/G 预测了 HLA-DPB1 表达增加的易感性。HLA-DPB1 等位基因、eplet 或 TerEp 水平的错配,或接触供体 HLA-DPB1 高表达与 HLA-DPB1 抗体形成均无显著相关性。然而,HLA-DPB1 eplet 和 TerEp 错配对移植物存活率有显著的负面影响(p<0.001 和 p=0.003)。与 HLA-DPB1 等位基因相比,在表位水平上匹配似乎有可能改善肾移植中的移植物存活率。

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