1 Laboratory of Nephrology, IDIBELL, Barcelona, Spain. 2 Division of Transplant Surgery, University of California, San Francisco, San Francisco, CA. 3 Kidney Transplant Unit, Bellvitge University Hospital, IDIBELL, UB, Barcelona, Spain.
Transplantation. 2017 Jun;101(6):1400-1409. doi: 10.1097/TP.0000000000001287.
Subclinical acute rejection (sc-AR) is a main cause for functional decline and kidney graft loss and may only be assessed through surveillance biopsies.
The predictive capacity of 2 novel noninvasive blood biomarkers, the transcriptional kidney Solid Organ Response Test (kSORT), and the IFN-γ enzyme-linked immunosorbent spot assay (ELISPOT) assay were assessed in the Evaluation of Sub-Clinical Acute rejection PrEdiction (ESCAPE) Study in 75 consecutive kidney transplants who received 6-month protocol biopsies. Both assays were run individually and in combination to optimize the use of these techniques to predict sc-AR risk.
Subclinical acute rejection was observed in 22 (29.3%) patients (17 T cell-mediated subclinical rejection [sc-TCMR], 5 antibody-mediated subclinical rejection [sc-ABMR]), whereas 53 (70.7%) showed a noninjured, preserved (stable [STA]) parenchyma. High-risk (HR), low-risk, and indeterminate-risk kSORT scores were observed in 15 (20%), 50 (66.7%), and 10 (13.3%) patients, respectively. The ELISPOT assay was positive in 31 (41%) and negative in 44 (58.7%) patients. The kSORT assay showed high accuracy predicting sc-AR (specificity, 98%; positive predictive value 93%) (all sc-ABMR and 58% sc-TCMR showed HR-kSORT), whereas the ELISPOT showed high precision ruling out sc-TCMR (specificity = 70%, negative predictive value = 92.5%), but could not predict sc-ABMR, unlike kSORT. The predictive probabilities for sc-AR, sc-TCMR, and sc-ABMR were significantly higher when combining both biomarkers (area under the curve > 0.85, P < 0.001) and independently predicted the risk of 6-month sc-AR in a multivariate regression analysis.
Combining a molecular and immune cell functional assay may help to identify HR patients for sc-AR, distinguishing between different driving alloimmune effector mechanisms.
亚临床急性排斥反应（sc-AR）是导致肾功能下降和移植物丢失的主要原因，只能通过监测活检来评估。
在 75 例连续接受 6 个月方案活检的肾移植患者中，评估了 2 种新型非侵入性血液生物标志物，即转录肾脏实体器官反应测试（kSORT）和干扰素-γ酶联免疫斑点测定（ELISPOT）的预测能力。单独和联合使用这两种检测方法来优化这些技术，以预测 sc-AR 风险。
22 例（29.3%）患者发生亚临床急性排斥反应（17 例 T 细胞介导的亚临床排斥反应[sc-TCMR]，5 例抗体介导的亚临床排斥反应[sc-ABMR]），而 53 例（70.7%）显示非损伤、保存（稳定[STA]）的实质。高风险（HR）、低风险和不确定风险 kSORT 评分分别见于 15 例（20%）、50 例（66.7%）和 10 例（13.3%）患者。ELISPOT 检测阳性 31 例（41%），阴性 44 例（58.7%）。kSORT 检测对 sc-AR 具有高准确性（特异性 98%；阳性预测值 93%）（所有 sc-ABMR 和 58%sc-TCMR 显示 HR-kSORT），而 ELISPOT 对排除 sc-TCMR 具有高精度（特异性=70%，阴性预测值=92.5%），但不能预测 sc-ABMR，与 kSORT 不同。当联合使用这两种生物标志物时，sc-AR、sc-TCMR 和 sc-ABMR 的预测概率显著升高（曲线下面积>0.85，P<0.001），并且在多变量回归分析中独立预测了 6 个月 sc-AR 的风险。
联合使用分子和免疫细胞功能检测可以帮助识别 sc-AR 的 HR 患者，区分不同的同种异体效应机制。
