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肾移植患者CD8 + T细胞上CTLA-4基因表达水平的评估及其与血清sCTLA-4水平的关系。

Assessment of CTLA-4 Gene Expression Levels on CD8+ T Cells in Renal Transplant Patients and Relation with Serum sCTLA-4 Levels.

作者信息

Çerçi Alkaç Burcu, Soyöz Mustafa, Pehlivan Melek, Kılıçaslan Ayna Tülay, Tatar Erhan, Karahan Çöven H İlayhan, Tanrısev Mehmet, Pirim İbrahim

机构信息

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

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

出版信息

Biochem Genet. 2025 Feb;63(1):526-539. doi: 10.1007/s10528-024-10723-7. Epub 2024 Mar 11.

Abstract

CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) is an immune regulator molecule that is expressed on a variety of immune cells, including CD4+ and CD8+ T cells. After realizing the significance of this regulator molecule, researchers began to concentrate on its activation or inhibition in cancer. Even though there have been some studies on organ transplantation and autoimmunity, the role of the CTLA-4 molecule in renal transplantation has not been demonstrated. The goal of this study was to see how CTLA-4 gene expression and serum sCTLA-4 levels affected renal transplant patients. Peripheral blood samples were collected before and 1-3 months after renal transplantation from 29 recipients. CD8+ T lymphocytes were separated using magnetic beads and purity of the cells controlled by Flow cytometry. CTLA-4 mRNA levels were determined by Real-Time PCR while serum sCTLA-4 levels were assessed by ELISA. 55% of the patient had decreased level of CTLA-4 mRNA after transplantation when compared to pre-transplantation levels. Moreover 61% of the patient had lower serum sCTLA-4 levels after transplantation. sCTLA-4 levels were decreased 11% of the patients with rejection episode after transplantation when compared to stabile patients (5%). Kidney rejection is a complicated process influenced by numerous unknown factors. Several parameters should be evaluated together to precise rejection episodes or graft dysfunctions. Further research focused on the other immune checkpoint regulator molecules could give an opportunity to have an idea about the effect of these molecules on renal transplantation.

摘要

细胞毒性T淋巴细胞相关抗原4(CTLA-4)是一种免疫调节分子,表达于多种免疫细胞,包括CD4+和CD8+ T细胞。在认识到这种调节分子的重要性后,研究人员开始关注其在癌症中的激活或抑制作用。尽管已经有一些关于器官移植和自身免疫的研究,但CTLA-4分子在肾移植中的作用尚未得到证实。本研究的目的是观察CTLA-4基因表达和血清可溶性CTLA-4(sCTLA-4)水平如何影响肾移植患者。从29名肾移植受者移植前及移植后1 - 3个月采集外周血样本。使用磁珠分离CD8+ T淋巴细胞,并通过流式细胞术控制细胞纯度。通过实时定量聚合酶链反应(Real-Time PCR)测定CTLA-4 mRNA水平,同时采用酶联免疫吸附测定(ELISA)评估血清sCTLA-4水平。与移植前水平相比,55%的患者移植后CTLA-4 mRNA水平降低。此外,61%的患者移植后血清sCTLA-4水平较低。与稳定患者(5%)相比,移植后发生排斥反应的患者中有11%的sCTLA-4水平降低。肾排斥是一个受众多未知因素影响的复杂过程。应综合评估多个参数以准确判断排斥反应或移植物功能障碍。进一步针对其他免疫检查点调节分子的研究可能为了解这些分子对肾移植的影响提供契机。

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