Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
PLoS One. 2012;7(6):e39610. doi: 10.1371/journal.pone.0039610. Epub 2012 Jun 29.
Studies in the past have shown that perforin expression is up-regulated during acute renal rejection, which provided hopes for a non-invasive and reliable diagnostic method to identify acute rejection. However, a systematic assessment of the value of perforin as a diagnostic marker of acute renal rejection has not been performed. We conducted this meta-analysis to document the diagnostic performance of perforin mRNA detection and to identify potential variables that may affect the performance.
METHODOLOGY/PRINCIPAL FINDINGS: Relevant materials that reported the diagnostic performance of perforin mRNA detection in acute renal rejection patients were extracted from electronic databases. After careful evaluation of the studies included in this analysis, the numbers of true positive, true negative, false positive and false negative cases of acute renal rejection identified by perforin mRNA detection were gathered from each data set. The publication year, sample origin, mRNA quantification method and housekeeping gene were also extracted as potential confounding variables. Fourteen studies with a total of 501 renal transplant subjects were included in this meta-analysis. The overall performance of perforin mRNA detection was: pooled sensitivity, 0.83 (95% confidence interval: 0.78 to 0.88); pooled specificity, 0.86 (95% confidence interval: 0.82 to 0.90); diagnostic odds ratio, 28.79 (95% confidence interval: 16.26 to 50.97); and area under the summary receiver operating characteristic curves value, 0.9107±0.0174. The univariate analysis of potential variables showed some changes in the diagnostic performance, but none of the differences reached statistical significance.
CONCLUSIONS/SIGNIFICANCE: Despite inter-study variability, the test performance of perforin mRNA detected by polymerase chain reaction was consistent under circumstances of methodological changes and demonstrated both sensitivity and specificity in detecting acute renal rejection. These results suggest a great diagnostic potential for perforin mRNA detection as a reliable marker of acute rejection in renal allograft recipients.
过去的研究表明，穿孔素表达在急性肾排斥反应中上调，这为寻找一种非侵入性和可靠的诊断方法来识别急性排斥反应提供了希望。然而，尚未对穿孔素作为急性肾排斥诊断标志物的价值进行系统评估。我们进行了这项荟萃分析，以记录穿孔素 mRNA 检测的诊断性能，并确定可能影响其性能的潜在变量。
方法/主要发现：从电子数据库中提取了报道穿孔素 mRNA 检测在急性肾排斥患者中的诊断性能的相关材料。仔细评估了本分析中包含的研究后，从每个数据集收集了穿孔素 mRNA 检测识别的急性肾排斥的真阳性、真阴性、假阳性和假阴性病例数。还提取了出版年份、样本来源、mRNA 定量方法和管家基因作为潜在混杂变量。这项荟萃分析共纳入了 14 项研究，共 501 例肾移植患者。穿孔素 mRNA 检测的总体性能为：合并敏感性为 0.83（95%置信区间：0.78 至 0.88）；合并特异性为 0.86（95%置信区间：0.82 至 0.90）；诊断优势比为 28.79（95%置信区间：16.26 至 50.97）；汇总受试者工作特征曲线下面积值为 0.9107±0.0174。潜在变量的单变量分析显示，诊断性能存在一些变化，但没有任何差异达到统计学意义。
结论/意义：尽管存在研究间的变异性，但聚合酶链反应检测到的穿孔素 mRNA 的检测性能在方法学变化的情况下保持一致，并且在检测急性肾排斥方面具有敏感性和特异性。这些结果表明，穿孔素 mRNA 检测作为肾移植受者急性排斥的可靠标志物具有很大的诊断潜力。
