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将CD4+ T细胞中白细胞介素-2、干扰素-γ和白细胞介素-4的表达及甲基化水平作为肾移植排斥反应预测指标的考量

Consideration of IL-2, IFN-γ and IL-4 expression and methylation levels in CD4+ T cells as a predictor of rejection in kidney transplant.

作者信息

Soyoz Mustafa, Pehlivan Melek, Tatar Erhan, Cerci Burcu, Coven Hatice Ilayhan Karahan, Ayna Tulay Kilicaslan

机构信息

Izmir Katip Celebi University, Faculty of Medicine, Department of Medical Biology, Izmir, Turkey.

Izmir Katip Celebi University, Vocational School of Health Services, Izmir, Turkey.

出版信息

Transpl Immunol. 2021 Oct;68:101414. doi: 10.1016/j.trim.2021.101414. Epub 2021 May 24.

DOI:10.1016/j.trim.2021.101414
PMID:34044071
Abstract

Kidney transplantation is the certain treatment for the end-stage-kidney disease patients. However after transplantation, allograft rejection or graft dysfunction are serious problems which the patients can be encountered. In several studies new biomarkers to predict rejection episodes tried to be evaluated and cytokines are thought to be one of these biomarkers. Additionally, epigenetic regulation of the cytokine genes can be an opportunity to detect the graft survival or dysfunction that lead to rejection. In this study, we aimed to detect the expression levels and methylation profile of cytokines IL-2, IL-4 and IFN-γ to follow the clinical situation of the patients. 25 kidney transplant patients were included in our study group and peripheral blood samples were collected before and 6 months after transplantation. CD4+ T cells were separated by using magnetic separation system and expression levels are detected by qPCR while methylation profile analysis was performed by pyrosequencing. According to our study we noticed that all of the patients with allograft rejection have increased expression levels of IFN-γ. When methylation profile of the CpGs in the promotor region of IFN-γ is evaluated, +128CpG was found as methylated when compared with +122. In conclusion, epigenetic mechanisms can effect several processed in renal transplantation and further studies with higher numbers of patients are needed to detect new biomarkers for prediction of allograft rejection.

摘要

肾移植是终末期肾病患者的确定性治疗方法。然而,移植后,同种异体移植排斥或移植物功能障碍是患者可能遇到的严重问题。在几项研究中,试图评估用于预测排斥反应发作的新生物标志物,细胞因子被认为是这些生物标志物之一。此外,细胞因子基因的表观遗传调控可能是检测导致排斥反应的移植物存活或功能障碍的一个契机。在本研究中,我们旨在检测细胞因子白细胞介素-2(IL-2)、白细胞介素-4(IL-4)和干扰素-γ(IFN-γ)的表达水平和甲基化谱,以跟踪患者的临床情况。我们的研究组纳入了25例肾移植患者,并在移植前和移植后6个月采集外周血样本。使用磁性分离系统分离CD4+T细胞,通过定量聚合酶链反应(qPCR)检测表达水平,同时通过焦磷酸测序进行甲基化谱分析。根据我们的研究,我们注意到所有发生同种异体移植排斥的患者IFN-γ的表达水平均升高。当评估IFN-γ启动子区域中胞嘧啶-磷酸-鸟嘌呤(CpG)的甲基化谱时,发现+128CpG与+122相比呈甲基化状态。总之,表观遗传机制可影响肾移植中的多个过程,需要对更多患者进行进一步研究,以检测预测同种异体移植排斥的新生物标志物。

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Consideration of IL-2, IFN-γ and IL-4 expression and methylation levels in CD4+ T cells as a predictor of rejection in kidney transplant.将CD4+ T细胞中白细胞介素-2、干扰素-γ和白细胞介素-4的表达及甲基化水平作为肾移植排斥反应预测指标的考量
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The Role of Dynamic DNA Methylation in Liver Transplant Rejection in Children.
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Transplant Direct. 2022 Oct 14;8(11):e1394. doi: 10.1097/TXD.0000000000001394. eCollection 2022 Nov.
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The applications of DNA methylation as a biomarker in kidney transplantation: a systematic review.DNA 甲基化作为肾移植生物标志物的应用:系统评价。
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