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register hereBackground: Antibody-mediated rejection is a significant cause of kidney transplant failure. Recent studies have shown that the MHC class I MICA gene influences the transplantation outcome. However, the role of the primary MICA receptor, NKG2D, has yet to be explored.We aimed to investigate the correlation between recipient/donor MICA allele matching and NKG2D genotype with the risk of antibody-mediated rejection and their potential clinical effects and implications for organ maintenance therapy.Of the 524 patients who underwent transplantation, 387 were eligible for the study.

背景：抗体介导的排斥反应是肾移植失败的重要原因。最近的研究表明，MHC I类MICA基因影响移植结果。然而，尚未探索主要MICA受体NKG2D的作用。我们旨在研究受体/供体MICA等位基因匹配和NKG2D基因型与抗体介导的排斥反应风险及其潜在的临床效果和对器官维持治疗的影响之间的相关性。在524名接受移植的患者中，387名符合研究条件。

Complete MICA allele and two functional polymorphisms of NKG2D (rs1049174C>G and rs2255336G>A) were analyzed in 148 transplanted patients and 146 controls.Results: Increased recipient/donor MICA allele mismatches correlate with an elevated risk of antibody-mediated rejection (X 2 =6.95; Log-rank=0.031).

在148例移植患者和146例对照中分析了完整的MICA等位基因和NKG2D的两个功能多态性（rs1049174C G和rs2255336G A）。结果：受体/供体MICA等位基因错配增加与抗体介导的排斥反应风险升高相关（X 2=6.95；对数秩=0.031）。

Notably, the rs1049174[GG] genotype contributes to a significantly increased risk of antibody-mediated rejection (X 2 =13.44; Log-rank=0.001 and X 2 =0.34; Log-rank=0.84). The combined effect of two MICA allele mismatches and rs1049174 [GG] genotype shows the highest risk (X 2 =23.21; Log-rank<0.001).

值得注意的是，rs1049174[GG]基因型导致抗体介导的排斥反应风险显着增加（X 2=13.44；对数秩=0.001和X 2=0.34；对数秩=0.84）。两个MICA等位基因错配和rs1049174[GG]基因型的联合作用显示出最高的风险（X 2=23.21；对数秩<0.001）。

Most importantly, patients with rs1049174[GG] and rs2255336 [AA] genotypes may respond less to mTOR inhibitor immunosuppressive therapy than Calcineurin inhibitors (rs1049174[GG]; P=0.035; and rs2255336[AA]; P=0.002).Recipient/donor MICA allele mismatches and specific NKG2D variants, as well as their combinations, influence kidney transplant outcomes, providing insights for personalized treatment and enhancing graft survival..

最重要的是，rs1049174[GG]和rs2255336[AA]基因型的患者对mTOR抑制剂免疫抑制治疗的反应可能比钙调神经磷酸酶抑制剂（rs1049174[GG]；P=0.035；和rs2255336[AA]；P=0.002）少。受体/供体MICA等位基因错配和特定NKG2D变体及其组合影响肾移植结果，为个性化治疗和提高移植物存活率提供见解。。