Organ Transplantation Institute, 309th Hospital of the Chinese People's Liberation Army, 17th Heishanhu Road, Haidian District Beijing, 100091, China.
J Clin Immunol. 2013 Jan;33(1):280-7. doi: 10.1007/s10875-012-9777-x. Epub 2012 Sep 5.
The outcome of renal transplantation is difficult to predict, even with an allograft biopsy. The aim of this study was to develop a sensitive, specific and noninvasive method for prediction of acute cellular rejection (ACR).
Luminex analysis was used to determine the levels of 95 cytokines/chemokines and their soluble receptors in sera from recipients with: ACR (in the first month post-transplantation, before and during rejection, and after rejection reversal); stable allograft function; delayed graft function (DGF); pulmonary infection. Evaluation of significant differential protein expression in ACR patients compared with stable allograft controls revealed a three-analyte combination as a marker of renal transplantation outcome. The predictive value of this combination was further validated in DGF and infection groups and in a blind binary code study of 24 additional serum samples.
Significant differential expression was detected in 26 proteins expressed in patients during the period preceding an ACR episode compared with stable controls. A blood test for discrimination of such patients was developed based on the simultaneous quantification of three analytes (IL-1 receptor antagonist, IL-20 and sCD40 ligand). This test exhibited 90.9 % sensitivity, 96 % specificity, a positive predictive value (PPV) of 95.2 % and a negative predictive value (NPV) of 92.3 %. Moreover, this combination allowed discrimination between patients with ACR and DGF and pulmonary infection.
With further development and validation, this blood test can be used to predict ACR and direct the treatment of transplant patients in the clinic.
即使进行同种异体移植活检，肾移植的结果也难以预测。本研究旨在开发一种灵敏、特异、非侵入性的方法来预测急性细胞排斥反应（ACR）。
采用 Luminex 分析法测定接受者血清中 95 种细胞因子/趋化因子及其可溶性受体的水平，这些接受者的情况包括：ACR（移植后第一个月，在排斥反应前、中、后）；稳定的同种异体移植物功能；延迟移植物功能（DGF）；肺部感染。与稳定的同种异体对照相比，评估 ACR 患者中差异显著的蛋白质表达，显示三种分析物组合是肾移植结果的标志物。该组合在 DGF 和感染组中的预测价值以及对 24 个额外血清样本的盲二进制代码研究中得到了进一步验证。
在 ACR 发作前与稳定对照组相比，26 种蛋白质在患者中表达差异显著。基于三种分析物（白细胞介素 1 受体拮抗剂、白细胞介素 20 和可溶性 CD40 配体）的同时定量，开发了一种用于区分此类患者的血液检测。该检测的灵敏度为 90.9%，特异性为 96%，阳性预测值（PPV）为 95.2%，阴性预测值（NPV）为 92.3%。此外，该组合可区分 ACR 患者与 DGF 和肺部感染患者。
经过进一步开发和验证，这种血液检测可用于预测 ACR，并在临床上指导移植患者的治疗。
