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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
Sabah Farouk El-Abd, Nagwa Mansour Badr Eldin, Salwa Elsaid, Nora Abdel Sameaa Ahmed, Eman Salah El-Shafey, Eslam Elsherbiny

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对埃及患者长期肾移植结果的影响

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细胞毒性免疫反应(CD3)的可行性。它包括152位肾脏接受者,分为两个亚组:76位稳定的移植功能(SGF)和76位同种异体移植功能障碍(AD),而对照组为56位健康个体。使用ARMS-PCR技术表征TNF-α-308 G> A和IFN-γ+ 874 A> T的遗传多态性。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组之间观察到了TNF-a-308 G / A的统计学差异(OR = 0.296,95%CI = 0.091–0.965,p= .031)的是AG基因型(中间生产者基因型)。此外,与SGF组相比,AD组显示出IFN-γ+ 874 TT(高生产者基因型)的统计学显着增加(OR = 0.290,95%CI = 0.127-0.665,p = .003)。具有同种异体功能障碍的接受者的CD3 + T淋巴细胞的表达在统计学上高于具有稳定同种异体功能的接受者和对照组(分别为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(SNPs)可能与肾移植后排斥的趋势有关。CD3可用作非排斥性生物标志物,用于监测排斥反应,并避免使患者暴露于活检风险和取样误差。

更新日期:2020-08-17
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