Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Transpl Immunol. 2019 Jun;54:9-16. doi: 10.1016/j.trim.2018.10.007. Epub 2018 Nov 3.
T cell immunoglobulin and mucin domain 3 (TIM-3), as a co-inhibitory receptor expressed on Th1, Th17, CD8T, FoxP3 + Treg and innate immune cells, plays an important role in suppression of T cell-mediated immune responses, tolerance induction and T cell exhaustion. In this study, we evaluated sequential alterations of TIM-3 mRNA expression level in blood and urine samples of renal transplant recipients to predict approaching clinical episodes.
A total of 52 adult renal transplant recipients (31 male and 21 female) were enrolled in this study. All the patients received kidney transplant from living unrelated donors. TIM-3 mRNA expression in peripheral blood mononuclear cells (PBMCs) and urinary cells were quantified using Real Time TaqMan polymerase chain reaction (PCR) at 4 different time points (pre-transplantation, 2, 90 and 180 days post-transplantation).
TIM-3 mRNA expression level on days 2, 90 and 180 after transplantation was significantly higher in blood and urine samples of patients with graft dysfunction (GD) compared with patients with well-functioning graft (WFG). Our results also showed a high correlation between blood and urinary level of TIM-3 mRNA expression. The data from Receiver Operating Characteristic (ROC) Curve Analysis showed that blood and urinary TIM-3 mRNA expression level at month 3 and 6 could discriminate graft dysfunction (GD) from well-functioning graft (WFG) with high specificity and sensitivity.
Our data suggested that serial monitoring of TIM-3 mRNA level in the blood and urine samples of renal transplant recipients could be a useful non-invasive biomarker for prediction and diagnosis of allograft dysfunction.
T 细胞免疫球蛋白和粘蛋白结构域 3（TIM-3）作为一种共抑制受体，表达于 Th1、Th17、CD8T、FoxP3+Treg 和固有免疫细胞上，在抑制 T 细胞介导的免疫应答、诱导耐受和 T 细胞耗竭方面发挥重要作用。在这项研究中，我们评估了肾移植受者血液和尿液样本中 TIM-3mRNA 表达水平的连续变化，以预测即将发生的临床事件。
本研究共纳入 52 例成年肾移植受者（31 名男性和 21 名女性）。所有患者均接受活体无关供者的肾移植。在移植前、移植后 2、90 和 180 天，使用实时 TaqMan 聚合酶链反应（PCR）定量外周血单个核细胞（PBMC）和尿细胞中的 TIM-3mRNA 表达。
与肾功能良好的移植物（WFG）患者相比，移植后第 2、90 和 180 天，发生移植物功能障碍（GD）的患者血液和尿液样本中的 TIM-3mRNA 表达水平显著升高。我们的结果还显示血液和尿液中 TIM-3mRNA 表达水平之间存在高度相关性。受试者工作特征（ROC）曲线分析的数据表明，第 3 个月和第 6 个月血液和尿液 TIM-3mRNA 表达水平可区分移植物功能障碍（GD）和肾功能良好的移植物（WFG），具有较高的特异性和敏感性。
我们的数据表明，肾移植受者血液和尿液样本中 TIM-3mRNA 水平的连续监测可能是预测和诊断移植物功能障碍的一种有用的非侵入性生物标志物。
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