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杀伤细胞免疫球蛋白样受体(KIR)和 HLA 基因型影响同种异体肾移植的结局。

Killer immunoglobulin-like receptor (KIR) and HLA genotypes affect the outcome of allogeneic kidney transplantation.

机构信息

Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.

出版信息

PLoS One. 2012;7(9):e44718. doi: 10.1371/journal.pone.0044718. Epub 2012 Sep 13.

Abstract

BACKGROUND

Recipient NK cells may detect the lack of recipient's (i.e., self) HLA antigens on donor renal tissue by means of their killer cell immunoglobulin-like receptors (KIRs). KIR genes are differently distributed in individuals, possibly contributing to differences in response to allogeneic graft.

METHODOLOGY/PRINCIPAL FINDINGS: We compared frequencies of 10 KIR genes by PCR-SSP in 93 kidney graft recipients rejecting allogeneic renal transplants with those in 190 recipients accepting grafts and 690 healthy control individuals. HLA matching results were drawn from medical records. We observed associations of both a full-length KIR2DS4 gene and its variant with 22-bp deletion with kidney graft rejection. This effect was modulated by the HLA-B,-DR matching, particularly in recipients who did not have glomerulonephritis but had both forms of KIR2DS4 gene. In contrast, in recipients with glomerulonephritis, HLA compatibility seemed to be much less important for graft rejection than the presence of KIR2DS4 gene. Simultaneous presence of both KIR2DS4 variants strongly increased the probability of rejection. Interestingly, KIR2DS5 seemed to protect the graft in the presence of KIR2DS4fl but in the absence of KIR2DS4del.

CONCLUSIONS/SIGNIFICANCE: Our results suggest a protective role of KIR2DS5 in graft rejection and an association of KIR2DS4 with kidney rejection, particularly in recipients with glomerulonephritis.

摘要

背景

受者 NK 细胞可能通过其杀伤细胞免疫球蛋白样受体(KIR)检测供体肾脏组织中缺乏受者(即自身)HLA 抗原。KIR 基因在个体中的分布不同,可能导致对同种异体移植物反应的差异。

方法/主要发现:我们通过 PCR-SSP 比较了 93 例排斥同种异体肾移植的肾移植受者、190 例接受移植的受者和 690 例健康对照个体的 10 种 KIR 基因的频率。HLA 配型结果取自病历。我们观察到全长 KIR2DS4 基因及其 22-bp 缺失变体与肾移植排斥的关联。这种效应受 HLA-B、-DR 匹配的调节,特别是在没有肾小球肾炎但同时具有两种 KIR2DS4 基因形式的受者中。相比之下,在患有肾小球肾炎的受者中,HLA 相容性似乎对移植物排斥的重要性远低于 KIR2DS4 基因的存在。两种 KIR2DS4 变体同时存在强烈增加了排斥的可能性。有趣的是,在存在 KIR2DS4fl 的情况下,KIR2DS5 似乎可以保护移植物,但在不存在 KIR2DS4del 的情况下则不会。

结论/意义:我们的研究结果表明 KIR2DS5 在移植物排斥中具有保护作用,而 KIR2DS4 与肾排斥相关,特别是在患有肾小球肾炎的受者中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7913/3441441/9047a50e7ef8/pone.0044718.g001.jpg

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