Department of Urology, the First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, People's Republic of China.
Transplantation. 2015 Jul;99(7):1477-86. doi: 10.1097/TP.0000000000000567.
Previous studies have reported that granzyme B (GZMB) and perforin (PRF) could serve as noninvasive biomarkers in the diagnosis of acute rejection (AR) after kidney transplant. Yet, their noninvasive diagnostic value in clinical practice is still unknown.
To assess the noninvasive diagnostic performance of GZMB and PRF for AR, we performed a systematic search. After reviewing published studies in which both GZMB and PRF were detected, data on the diagnostic accuracy of separate and combined evaluation of GZMB and PRF were pooled.
Across 16 studies (680 subjects), summary sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios with 95% confidence intervals were calculated. For overall GZMB analysis, the indices were 0.76 (0.71-0.81), 0.86 (0.82-0.89), 4.58 (3.36-6.25), and 0.32 (0.22-0.47), respectively. For overall PRF analysis, the indices were 0.83 (0.78-0.88), 0.86 (0.82-0.89), 4.82 (3.66-6.35), and 0.26 (0.18-0.37), respectively. Subgroup analyses showed similar results compared to overall study analyses. In analyses of combined evaluation of GZMB and PRF, the above indices were 0.65 (0.53-0.76), 0.96 (0.91-0.98), 12.66 (5.83-27.50), and 0.40 (0.23-0.69), respectively, when both markers were positive. The probability of developing AR in kidney transplant recipients increased from 15% to 73% when both GZMB and PRF tests were positive and was reduced to 2% if that were negative.
Currently, neither GZMB nor PRF, if evaluated alone, could be a convincing noninvasive diagnostic marker for AR in clinical practice. Combined use of PRF and GZMB post-kidney transplant may be a better choice in AR evaluation to direct allograft biopsy execution and earlier therapeutic intervention.
先前的研究报告称，颗粒酶 B（GZMB）和穿孔素（PRF）可作为肾移植后急性排斥反应（AR）的非侵入性生物标志物。然而，它们在临床实践中的非侵入性诊断价值尚不清楚。
为了评估 GZMB 和 PRF 对 AR 的非侵入性诊断性能，我们进行了系统搜索。在回顾了同时检测 GZMB 和 PRF 的已发表研究后，汇总了单独和联合评估 GZMB 和 PRF 的诊断准确性数据。
在 16 项研究（680 例患者）中，计算了汇总敏感性、特异性、阳性似然比和阴性似然比及其 95%置信区间。对于整体 GZMB 分析，这些指标分别为 0.76（0.71-0.81）、0.86（0.82-0.89）、4.58（3.36-6.25）和 0.32（0.22-0.47）。对于整体 PRF 分析，这些指标分别为 0.83（0.78-0.88）、0.86（0.82-0.89）、4.82（3.66-6.35）和 0.26（0.18-0.37）。亚组分析结果与整体研究分析相似。在 GZMB 和 PRF 联合评估分析中，当两个标志物均为阳性时，上述指标分别为 0.65（0.53-0.76）、0.96（0.91-0.98）、12.66（5.83-27.50）和 0.40（0.23-0.69）。当两个 GZMB 和 PRF 检测均为阳性时，肾移植受者发生 AR 的概率从 15%增加到 73%，而如果均为阴性，则降低至 2%。
目前，单独评估 GZMB 或 PRF 均不能成为临床实践中令人信服的 AR 非侵入性诊断标志物。肾移植后联合使用 PRF 和 GZMB 可能是评估 AR 的更好选择，可指导进行同种异体移植物活检和早期治疗干预。
