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Impact of Proinflammatory Cytokine Gene Polymorphisms and Circulating CD3 on Long-Term Renal Allograft Outcome in Egyptian Patients
Immunological Investigations ( IF 2.8 ) Pub Date : 2020-08-17 , DOI: 10.1080/08820139.2020.1804398
Sabah Farouk El-Abd 1 , Nagwa Mansour Badr Eldin 2 , Salwa Mahmoud Elwasif 3 , Nora Abdel Sameaa Ahmed 1 , Eman Salah El-Shafey 4 , Eslam Elsherbiny 4
Affiliation  

ABSTRACT

The extant study aimed to explore the influence of two cytokines TNF-α − 308 and IFN-γ + 874 gene polymorphism on development of renal transplant rejection and to investigate the feasibility of Th1 cytotoxic immune reaction (CD3). It includes 152 kidney recipients were divided into two subgroups: 76 stable graft functions (SGF) and 76 allograft dysfunctions (AD) compared with 56 healthy individuals as control group. TNF-α − 308 G > A and IFN-γ + 874 A > T genetic polymorphisms were characterized using ARMS-PCR technique. CD3 protein expression was measured using ELISA Kit. The effect on transplant outcome was analyzed where, statistically significant differences of TNF-a-308 G/A were observed between AD group when compared to SGF group (OR = 0.296, 95% CI = 0.091–0.965, p = .031) in AG genotype (intermediate producer genotype). Also, AD group displayed a statistically significant increase of IFN-γ + 874 TT (high producer genotype) when compared to SGF group (OR = 0.290, 95% CI = 0.127–0.665, p = .003). The expression of CD3+ T lymphocytes in recipients with allograft dysfunction was statistically higher than that with stable allograft function and control groups (732 ± 76, 235 ± 51 and 442 ± 50) respectively and (p ≤ 0.001). In conclusion, IFN-γ + 874 T and TNF-α − 308 A alleles are risk alleles for renal transplant rejection and these two single nucleotide polymorphisms (SNPs) may be implicated in the tendency of rejection after renal transplantation. CD3 may be used as non-invasive biomarker in monitoring of rejection and avoid exposing patients for biopsy risks and sampling error.



中文翻译:

促炎细胞因子基因多态性和循环 CD3 对埃及患者长期肾脏同种异体移植结果的影响

摘要

现有研究旨在探讨两种细胞因子 TNF-α - 308 和 IFN-γ + 874 基因多态性对肾移植排斥反应发展的影响,并探讨 Th1 细胞毒免疫反应 (CD3) 的可行性。它包括 152 名肾脏受者,分为两个亚组:76 名稳定的移植物功能(SGF)和 76 名同种异体移植物功能障碍(AD)与 56 名健康个体作为对照组。使用 ARMS-PCR 技术表征 TNF-α - 308 G > A 和 IFN-γ + 874 A > T 基因多态性。使用 ELISA 试剂盒测量 CD3 蛋白表达。分析了对移植结果的影响,与 SGF 组相比,AD 组之间观察到 TNF-a-308 G/A 的统计学显着差异(OR = 0.296, 95% CI = 0.091–0.965, p= .031)在 AG 基因型(中间生产者基因型)中。此外,与 SGF 组相比,AD 组的 IFN-γ + 874 TT(高生产基因型)显着增加(OR = 0.290, 95% CI = 0.127–0.665, p = .003)。同种异体移植物功能障碍受者CD3 + T淋巴细胞的表达高于同种异体移植物功能稳定组和对照组(732±76、235±51和442±50)和(p≤ 0.001)。总之,IFN-γ + 874 T 和 TNF-α - 308 A 等位基因是肾移植排斥的风险等位基因,这两个单核苷酸多态性(SNP)可能与肾移植后排斥的趋势有关。CD3 可用作监测排斥反应的非侵入性生物标志物,并避免使患者面临活检风险和取样错误。

更新日期:2020-08-17
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