Shahbaz Sanaz Keshavarz, Pourrezagholi Fatemeh, Barabadi Mehri, Foroughi Farshad, Hosseinzadeh Morteza, Ahmadpoor Pedram, Nafar Mohesn, Yekaninejad Mir Saeed, Amirzargar Aliakbar
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.
Chronic Kidney Disease Research Center, Department of Nephrology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Transpl Immunol. 2017 Aug;43-44:11-20. doi: 10.1016/j.trim.2017.07.002. Epub 2017 Jul 27.
T cell immunoglobulin and mucin domain 3 (TIM-3) is involved in alloimmune and autoimmune responses, as well as tolerance induction in kidney transplantation. Kidney injury molecule-1 (KIM-1) is highly expressed in epithelial cells of the injured proximal tubule. In this study, we have investigated both urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins in renal allograft recipients diagnosed with acute allograft rejection (AR) and chronic allograft dysfunction (CAD), as well as those with well-functioning transplants (WFG).
We divided 85 patients into the following groups: AR (n=24), CAD (n=19), and WFG (n=42). TIM-3 and KIM-1 mRNA expressions were quantified using real-time reverse-transcription TaqMan probe polymerase chain reaction (RT-PCR). An ELISA test was used to measure the amount of KIM-1 protein in serum and urine samples.
AR and CAD patients had significantly greater urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins compared to WFG patients. Receiver operating characteristic (ROC) analysis showed that these molecules discriminated Allograft rejections from WFG.
Quantification of TIM-3 and KIM-1 mRNA expressions, along with KIM-1 protein measurements in urine and blood could be employed as promising tools for noninvasive diagnosis of allograft dysfunction.
T细胞免疫球蛋白和粘蛋白结构域3（TIM-3）参与同种异体免疫和自身免疫反应，以及肾移植中的耐受性诱导。肾损伤分子1（KIM-1）在受损近端小管的上皮细胞中高表达。在本研究中，我们调查了诊断为急性移植排斥反应（AR）和慢性移植功能障碍（CAD）的肾移植受者以及移植功能良好（WFG）的受者的尿液和血液中TIM-3 mRNA表达、尿液中KIM-1 mRNA表达以及尿液和血清中KIM-1蛋白的情况。
我们将85例患者分为以下几组：AR组（n = 24）、CAD组（n = 19）和WFG组（n = 42）。使用实时逆转录TaqMan探针聚合酶链反应（RT-PCR）对TIM-3和KIM-1 mRNA表达进行定量。采用酶联免疫吸附测定（ELISA）试验测量血清和尿液样本中KIM-1蛋白的含量。
与WFG患者相比，AR和CAD患者的尿液和血液中TIM-3 mRNA表达、尿液中KIM-1 mRNA表达以及尿液和血清中KIM-1蛋白均显著更高。受试者工作特征（ROC）分析表明，这些分子能够区分移植排斥反应和WFG。
TIM-3和KIM-1 mRNA表达的定量分析，以及尿液和血液中KIM-1蛋白的检测，有望成为同种异体移植功能障碍无创诊断的工具。
