Joelsons G, Domenico T, Gonçalves L F, Manfro R C
Faculdade de Medicina, Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
Braz J Med Biol Res. 2018;51(7):e6904. doi: 10.1590/1414-431x20186904. Epub 2018 May 17.
The aim of the present study was to evaluate messenger RNA expression in kidney allograft recipients. Forty-four kidney transplant recipients were evaluated up to three months after grafting. After transplantation, peripheral blood samples were drawn sequentially for real-time polymerase chain reaction analyses of perforin and TIM-3 genes. Biopsies were obtained to evaluate acute graft dysfunction and interpreted according to the Banff classification. Eight patients presented episodes of acute rejection. Recipients with rejection had significantly higher levels of TIM-3 mRNA transcripts compared to those without rejection (median gene expression 191.2 and 36.9 mRNA relative units, respectively; P<0.0001). Also, perforin gene expression was higher in patients with rejection (median gene expression 362.0 and 52.8 mRNA relative units; P<0.001). Receiver operating characteristic curves showed that the area under the curve (AUC) for the TIM-3 gene was 0.749 (95%CI: 0.670-0.827). Perforin gene mRNA expression provided an AUC of 0.699 (95%CI: 0.599 to 0.799). Overall accuracy of gene expression was 67.9% for the TIM-3 gene and 63.6% for the perforin gene. Combined accuracy was 76.8%. Negative predictive values were 95.3% for the TIM-3 gene, 95.5% for the perforin gene, and 95.4% in the combined analyses. Gene expression was significantly modulated by rejection treatment decreasing 64.1% (TIM-3) and 90.9% (perforin) compared to the median of pre-rejection samples. In conclusion, the longitudinal approach showed that gene profiling evaluation might be useful in ruling out the diagnosis of acute rejection and perhaps evaluating the efficacy of treatment.
本研究的目的是评估肾移植受者中信使核糖核酸的表达。44名肾移植受者在移植后长达三个月的时间内接受了评估。移植后，依次采集外周血样本，用于对穿孔素和TIM-3基因进行实时聚合酶链反应分析。获取活检样本以评估急性移植功能障碍，并根据班夫分类法进行解读。8名患者出现急性排斥反应。与未发生排斥反应的受者相比，发生排斥反应的受者TIM-3信使核糖核酸转录物水平显著更高（基因表达中位数分别为191.2和36.9个信使核糖核酸相对单位；P<0.0001）。此外，发生排斥反应的患者穿孔素基因表达也更高（基因表达中位数为362.0和52.8个信使核糖核酸相对单位；P<0.001）。受试者工作特征曲线显示，TIM-3基因的曲线下面积（AUC）为0.749（95%CI：0.670 - 0.827）。穿孔素基因信使核糖核酸表达的AUC为0.699（95%CI：0.599至0.799）。TIM-3基因表达的总体准确率为67.9%，穿孔素基因的总体准确率为63.6%。联合准确率为76.8%。TIM-3基因的阴性预测值为95.3%，穿孔素基因的阴性预测值为95.5%，联合分析中的阴性预测值为95.4%。与排斥反应前样本的中位数相比，排斥反应治疗显著调节了基因表达，TIM-3降低了64.1%，穿孔素降低了90.9%。总之，纵向研究方法表明，基因谱评估可能有助于排除急性排斥反应的诊断，或许还能评估治疗效果。
