Killer Immunoglobulin-like Receptor (KIR) and HLA Genotypes Affect the Outcome of Allogeneic Kidney Transplantation
Killer Immunoglobulin-like Receptor (KIR) and HLA Genotypes Affect the Outcome of Allogeneic Kidney Transplantation
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DOI：
10.1371/journal.pone.0044718
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发表时间：
2012-09-13
期刊：
影响因子：
3.7
通讯作者：
Kusnierczyk, Piotr
中科院分区：
文献类型：
--
作者：
Nowak, Izabela;Magott-Procelewska, Maria;Kusnierczyk, Piotr
背景：NK细胞可以检测受体的缺乏（即，自身）HLA抗原通过其杀伤细胞免疫球蛋白样受体（KIR）作用于供体肾组织。KIR基因在个体中分布不同，可能导致对同种异体graft.Methodology/Principal Findings的反应差异：我们比较了10个KIR基因的频率，通过PCR-SSP在93个肾移植受者中排斥同种异体肾移植，在190个接受移植的受者和690个健康对照个体。HLA配型结果来自医疗记录。我们观察了全长KIR 2DS 4基因及其22 bp缺失变异体与肾移植排斥反应的相关性。这种效应受到HLA-B，-DR匹配的调节，特别是在没有肾小球肾炎但具有两种形式的KIR 2DS 4基因的受者中。相反，在肾小球肾炎的受体中，HLA相容性似乎比KIR 2DS 4基因的存在对移植物排斥反应的重要性小得多。两种KIR 2DS 4变体的同时存在强烈增加了排斥的可能性。有趣的是，KIR 2DS 5似乎在KIR 2DS 4fl存在时保护移植物，但在KIR 2DS 4del不存在时保护移植物。结论/意义：我们的结果表明KIR 2DS 5在移植物排斥中的保护作用，以及KIR 2DS 4与肾排斥的关联，特别是在患有肾小球肾炎的受者中。
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.