新型尿液外泌体生物标志物在肾移植受者急性 T 细胞介导排斥反应中的应用：一项横断面研究。
Novel urinary exosomal biomarkers of acute T cell-mediated rejection in kidney transplant recipients: A cross-sectional study.
机构信息
Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.
Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.
出版信息
PLoS One. 2018 Sep 18;13(9):e0204204. doi: 10.1371/journal.pone.0204204. eCollection 2018.
BACKGROUND
Acute rejection is hazardous to graft survival in kidney transplant recipients (KTRs). We aimed to identify novel biomarkers for early diagnosis of acute T cell-mediated rejection (TCMR) in urinary exosomes of KTRs.
METHODS
Among 458 graft biopsies enrolled in a cross-sectional multicenter study, 22 patients with stable graft function (STA) who had not shown pathologic abnormality and 25 patients who diagnosed biopsy-proven TCMR were analyzed. We performed proteomic analysis using nano-ultra performance liquid chromatography-tandem mass spectrometry (nano-UPLC-MS/MS) to identify candidate biomarkers for early TCMR diagnosis on urinary exosomes. We confirmed the protein levels of each candidate biomarker by western blot analysis.
RESULTS
A total of 169 urinary exosome proteins were identified by nano-UPLC-MS/MS. Forty-six proteins showed increased expression in STA patients, while 17 proteins were increased in TCMR patients. Among them, we selected five proteins as candidate biomarkers for early diagnosis of TCMR according to significance, degree of quantity variance, and information from the ExoCarta database. We confirmed the proteomic expression levels of five candidate biomarkers by western blot analysis in each patient. Of all candidate biomarkers, tetraspanin-1 and hemopexin were significantly higher in TCMR patients (STA:TCMR ratio = 1:1.8, P = 0.009, and 1:3.5, P = 0.046, respectively).
CONCLUSIONS
Tetraspanin-1 and hemopexin were detected in KTR urine and could act as potential diagnostic proteins for TCMR.
背景
急性排斥反应对肾移植受者（KTR）的移植物存活有危险。我们旨在鉴定 KTR 尿液外泌体中用于早期诊断急性 T 细胞介导排斥反应（TCMR）的新型生物标志物。
方法
在一项横断面多中心研究中，对 458 例移植活检患者进行了分析，其中 22 例具有稳定移植物功能（STA）的患者未显示病理异常，25 例患者诊断为活检证实的 TCMR。我们使用纳升级超高效液相色谱-串联质谱（nano-UPLC-MS/MS）进行蛋白质组分析，以鉴定用于早期 TCMR 诊断的尿液外泌体候选生物标志物。我们通过 Western blot 分析证实了每个候选生物标志物的蛋白水平。
结果
通过 nano-UPLC-MS/MS 鉴定了 169 种尿液外泌体蛋白。46 种蛋白在 STA 患者中表达增加，而 17 种蛋白在 TCMR 患者中增加。其中，我们根据显著性、数量方差程度和 ExoCarta 数据库的信息，选择了五种蛋白质作为 TCMR 早期诊断的候选生物标志物。我们通过 Western blot 分析在每位患者中均证实了五种候选生物标志物的蛋白质表达水平。在所有候选生物标志物中，四跨膜蛋白 1 和血红素结合蛋白在 TCMR 患者中显著升高（STA：TCMR 比值为 1:1.8，P = 0.009 和 1:3.5，P = 0.046）。
结论
四跨膜蛋白 1 和血红素结合蛋白在 KTR 尿液中被检测到，可能作为 TCMR 的潜在诊断蛋白。
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