Hu Rong, Barratt Daniel T, Coller Janet K, Sallustio Benedetta C, Somogyi Andrew A
Discipline of Pharmacology, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
Department of Clinical Pharmacology, The Queen Elizabeth Hospital, Adelaide, SA, Australia.
Front Pharmacol. 2020 Feb 20;10:1686. doi: 10.3389/fphar.2019.01686. eCollection 2019.
Innate immunity contributes to acute rejection after kidney transplantation. Genetic polymorphisms affecting innate immunity may therefore influence patients' risk of rejection. -330T > G, -1082G > A, -819C > T, and -592C > A, and -308G > A are not associated with acute rejection incidence in Caucasian kidney transplant recipients receiving a calcineurin inhibitor, ciclosporin or tacrolimus (TAC). However, other important innate immune genetic polymorphisms have not yet been extensively studied in recipients and donors. In addition, innate immunogenetics have not been investigated in kidney transplant cohorts receiving only TAC as the calcineurin inhibitor.
To investigate the effect of recipient and donor , , , , , , , , , , , and genetics on acute kidney rejection in the first 2 weeks post-transplant in TAC-treated kidney transplant recipients.
This study included 154 kidney transplant recipients and 81 donors successfully genotyped for 17 polymorphisms in these genes. All recipients were under triple immunosuppressant therapy of TAC, mycophenolate mofetil, and prednisolone. Recipient and donor genotype differences in acute rejection incidence within the first 2 weeks post-transplantation were assessed by logistic regression, adjusting for induction therapy, human leukocyte antigen mismatches, kidney transplant number, living donor, and peak panel-reactive antibody scores.
A trend (Cochran-Armitage P = 0.031) of increasing acute rejection incidence was observed from recipient -6331 T/T (18%) to T/C (25%) to C/C (46%) genotype [C/C versus T/T odds ratio (95% confidence interval) = 6.6 (1.7 to 25.8) (point-wise P = 0.017)]. However, no genotype differences were significant after Bonferroni correction for multiple comparisons.
This study did not detect any statistically significant effects of recipient or donor innate immune genetics on acute rejection incidence in the first 2 weeks post-transplantation. However, the sample size was small, and future larger studies or meta-analyses are required to demonstrate conclusively if innate immune genetics such as influence the risk of acute rejection after kidney transplantation.
固有免疫在肾移植后急性排斥反应中起作用。因此，影响固有免疫的基因多态性可能会影响患者的排斥风险。-330T>G、-1082G>A、-819C>T、-592C>A和-308G>A与接受钙调神经磷酸酶抑制剂环孢素或他克莫司（TAC）的白种人肾移植受者的急性排斥发生率无关。然而，其他重要的固有免疫基因多态性在受者和供者中尚未得到广泛研究。此外，在仅接受TAC作为钙调神经磷酸酶抑制剂的肾移植队列中，尚未对固有免疫遗传学进行研究。
研究受者和供者的[此处原文似乎有缺失基因相关信息]基因对接受TAC治疗的肾移植受者移植后前2周急性肾排斥反应的影响。
本研究纳入了154例肾移植受者和81例供者，成功对这些基因中的17种多态性进行了基因分型。所有受者均接受TAC、霉酚酸酯和泼尼松龙的三联免疫抑制治疗。通过逻辑回归评估移植后前2周内急性排斥发生率的受者和供者基因型差异，并对诱导治疗、人类白细胞抗原错配、肾移植次数、活体供者和峰值群体反应性抗体评分进行校正。
观察到从受者-6331 T/T基因型（18%）到T/C基因型（25%）再到C/C基因型（46%），急性排斥发生率有增加趋势（ Cochr an-Armitage P=0.031）[C/C与T/T比值比（95%置信区间）=6.6（1.7至25.8）（逐点P=0.017）]。然而，在进行多重比较的Bonferroni校正后，没有基因型差异具有统计学意义。
本研究未检测到受者或供者固有免疫遗传学对移植后前2周急性排斥发生率有任何统计学上的显著影响。然而，样本量较小，未来需要更大规模的研究或荟萃分析来最终证明诸如[此处原文似乎有缺失基因相关信息]等固有免疫遗传学是否会影响肾移植后急性排斥的风险。
