细胞因子基因多态性对肾移植急性排斥的影响

Effect of recipient cytokine genotypes on development of acute allograft rejection after renal transplantation

目的:研究肾移植受者的细胞因子和细胞因子受体基因多态性对术后早期发生急性排斥反应的影响.方法:①126名肾移植受者分为急性排斥组和无排斥组(6个月内),比较两组患者中可能影响肾移植急性排斥发生的可能因素、13种细胞因子及受体的22个位点基因型分布情况;②根据HLA-DR配型情况分成0～1个HLA-DR位点错配组、HLA-DR完全错配组,分别比较阳性基因多态性的各种基因型在排斥和无排斥患者中的分布情况.结果:①急性排斥患者中,HLA-DR错配数明显高于无排斥患者;白介素-1(IL-1)α-889C/C、IL-4Rα+1902 A/A、IL-12-1188C/C、IL-10(-1082-819--592)ATA/ATA、IL-10-819T/T、IL-10-592A/A及IL-10纯合子低表达型的频率明显高于无排斥的患者,IL-2+166T/T频率明显低于无排斥患者;②0～1个HLA-DR位点错配时,两组患者中IL-10的基因型频率明显不同,而在HLA-DR完全错配时,IL-4Rα+1902 A/G、IL-12-1188C/A、IL-2+166G/T基因型频率明显不同,所有差别均有统计学意义.结论:HLA-DR错配是肾移植术后发生急性排斥的危险因素,肾移植受者的IL-1α-889C/C、IL-4Rα+1902A/A、IL-12-1188C/C、IL-10(-1082-819--592)ATA/ATA、IL-10-819 T/T、IL-10-592 A/A、IL-10纯合子低表达型是发生排斥的遗传学危险因素,而IL-2+166T/T则是不发生排斥的一个安全指标;HLA-DR位点错配情况干扰这些细胞因子基因多态性对急性排斥的影响作用.

Objective:To investigate the impact of renal allograft recipient cytokine and cytokine receptor gene polymorphisms on acute renal rejection. Methodology:①According to the presence or absence of acute graft rejection, 126 cases of cadaveric renal allograft recipients were divided into two groups, between them the distribution of 22 polymorphisms in 13 cytokine and cytokine receptor genes were compared. ②After all recipients were stratified into two conditions: 0~1 locus HLA DR mismatched and HLA DR completely mismatched, previous positive gene polymorphisms were also compared with two groups. Results:①In the rejection group, the genotype frequency of IL 1α 889C/C, IL 4Rα+1902A/A, IL 12 1188C/C, IL 10 592A/A, IL 10 819T/T, IL 10( 1082 819 592)ATA/ATA and frequency of homozygosity for IL 10 Lower production type were significantly higher, whereas the genotype frequency of IL 2 +166T/T was significantly lower than those in no rejection group. ②With 0~1 locus HLA DR mismatched, the distribution of gene polymorphisms of IL 10 was significantly different between two groups. On the other hand, with HLA DR completely mismatched, the genotype frequency of IL 4Rα+1902 A/G, IL 12 1188C/A and IL 2 +166G/T were significantly different. Conclusion:This study identified recipient genotype of IL 1α 889 C/C, IL 4Rα+1902 A/A, IL 12 1188 C/C, IL 10 ( 1082 819 592) ATA/ATA, IL 10 819 T/T, IL 10 592 A/A and homozygosity of IL 10 lower production type as the major genetic risk factors and IL 2 +166T/T as a genetic safe factor for the development of acute allograft rejection. Furthermore, the condition of HLA DR mismatch might interfere the action of these cytokine and cytokine receptor polymorphisms.