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病毒感染与共刺激基因多态性在肾移植结局中的关联。

The Association Between Viral Infections and Co-stimulatory Gene Polymorphisms in Kidney Transplant Outcomes.

作者信息

Niknam Ahmad, Karimi Mohammad Hossein, Yaghobi Ramin, Geramizadeh Bita, Roozbeh Jamshid, Salehipour Mehdi, Iravani Mahdiyar

机构信息

Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran.

出版信息

Jundishapur J Microbiol. 2016 Feb 17;9(8):e31338. doi: 10.5812/jjm.31338. eCollection 2016 Aug.

Abstract

BACKGROUND

The surveillance of kidney transplant patients depends on function of different immunologic markers like co-stimulatory molecules. These molecules may also be associated with post kidney transplant viral related outcomes.

OBJECTIVES

The aim of this study was to investigate the possible associations between co-stimulatory molecule gene polymorphisms and viral infections in kidney transplant patients.

PATIENTS AND METHODS

In total, 172 kidney transplant patients were included in this study. Single nucleotide polymorphisms in loci of co-stimulatory molecules including: PDCD.1, CD28, CTLA4 and ICOS, were analyzed in the studied patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Active (CMV) infection and history of hepatitis C virus (HCV) infection were analyzed in each kidney transplant patient using the CMV antigenemia kit and HCV antibody assay, according to the manufacturer's instructions.

RESULTS

CMV active infection was found in 31 of 172 (18.02%) kidney transplant patients. HCV infection was only found in two of the 172 (1.16%) studied patients. Significant associations were found between TT and TC genotypes of CTLA4 -1722T/C and T allele with acute rejection in CMV infected kidney transplant patients. A significant association was also found between the T allele of CD28 + 17 C/T genetic polymorphism and acute rejection in CMV infected kidney transplant patients. Significantly higher frequency of AA genotype and A allele of CTLA4 + 49AG polymorphism were found in CMV infected female patients. Also a significantly higher frequency of GG genotype and G allele of PDCD-1.3A/G polymorphisms were found in CMV infected female patients.

CONCLUSIONS

Based on these results, CTLA4 and CD28 genetic polymorphisms, which regulate T-cell activation, can influence active CMV infection in kidney transplant patients. These results should be confirmed by further investigations.

摘要

背景

肾移植患者的监测依赖于不同免疫标志物的功能,如共刺激分子。这些分子也可能与肾移植后病毒相关结局有关。

目的

本研究旨在探讨共刺激分子基因多态性与肾移植患者病毒感染之间的可能关联。

患者与方法

本研究共纳入172例肾移植患者。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析研究患者共刺激分子位点(包括PDCD.1、CD28、CTLA4和ICOS)的单核苷酸多态性。根据制造商的说明,使用巨细胞病毒(CMV)抗原血症试剂盒和丙型肝炎病毒(HCV)抗体检测法分析每例肾移植患者的活动性CMV感染和HCV感染史。

结果

172例肾移植患者中有31例(18.02%)发现有活动性CMV感染。在172例研究患者中仅2例(1.16%)发现有HCV感染。在CMV感染的肾移植患者中,CTLA4 -1722T/C的TT和TC基因型以及T等位基因与急性排斥反应之间存在显著关联。在CMV感染的肾移植患者中,CD28 + 17 C/T基因多态性的T等位基因与急性排斥反应之间也存在显著关联。在CMV感染的女性患者中,CTLA4 + 49AG多态性的AA基因型和A等位基因频率显著更高。在CMV感染的女性患者中,PDCD-1.3A/G多态性的GG基因型和G等位基因频率也显著更高。

结论

基于这些结果,调节T细胞活化的CTLA4和CD28基因多态性可影响肾移植患者的活动性CMV感染。这些结果应通过进一步研究加以证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f411/5076488/60a3baa5b670/jjm-09-08-31338-i001.jpg

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