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TLR‐2, TLR‐4 and MyD88 genes expression in renal transplant acute and chronic rejections

机译:TLR-2,TLR-4和MYD88基因在肾移植急性和慢性排斥反应中的表达

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Abstract Background Graft rejection due to alloreactivity is still the main obstacle to successful renal transplantation. Toll‐like receptors (TLRs), which are significantly involved in initiating inflammation, triggering innate immunity, occurrence of ischaemia reperfusion injury (IRI) and subsequent deterioration of allograft function, are of interest in molecular diagnosis of graft rejection. Methods In present research, we have evaluated the mRNA expressions of TLR‐4, TLR‐2 and myeloid differentiation primary response gene 88 (MyD88) in peripheral blood mononuclear cells (PBMCs) and biopsy samples of 26 stable graft function (SGF), 14 acute T‐cell‐mediated rejection (ACMR), six acute antibody‐mediated rejection (AAMR), 10 chronic T‐cell‐mediated rejection (CCMR) and four chronic antibody‐mediated rejection (CAMR) cases of renal transplant recipients, using TaqMan detector real‐time polymerase chain reaction (RT‐PCR). Results It was found that TLR4 mRNA level was significantly elevated in PBMCs of both ACMR (P.v: 0.025) and CCMR (P.v: 0.007) cases, while TLR2 gene was upregulated only in PBMCs of ACMR (P.v: 0.024). Moreover, MyD88 expression was increased in biopsy samples of all rejection groups AAMR (P.v: 0.032), ACMR (P.v: 0.002), CAMR (P.v: 0.038) and CCMR (P.v: 0.013) and could distinguish them from stable grafts with AUC (area under curve) of 0.81, 0.80, 0.83 and 0.77, respectively. Conclusion These data showed that MyD88 gene upregulation in renal tissue could have diagnostic value and increased level of TLR4 mRNA in PBMCs could be suggestive of cell‐mediated rejections. Therefore, monitoring the expression level of inflammatory signalling genes might be useful in predicting allograft rejection.
机译:摘要背景引起的地移植抑制仍然是成功肾移植的主要障碍。易于涉及启动炎症,引发先天免疫力,缺血再灌注损伤(IRI)的发生以及随后对同种异体移植功能的劣化的影响的受体(TLRS)具有兴趣的侵袭性抑制的分子诊断。目前研究的方法,我们在外周血单核细胞(PBMC)中,评估了TLR-4,TLR-2和骨髓细分分化初级反应基因88(MYD88)的mRNA表达,以及26个稳定接枝函数(SGF)的活检样品,14急性T细胞介导的排斥(ACMR),六种急性抗体介导的排斥(AAMR),10慢性T细胞介导的排斥(CCMR)和四种慢性抗体介导的肾移植受者的抑制(CAMR)病例,使用Taqman检测器实时聚合酶链反应(RT-PCR)。结果发现,ACMR(P.V:0.025)和CCMR(P.V:0.007)病例的PBMC中,TLR4 mRNA水平显着升高,而TLR2基因仅在ACMR的PBMC(P.V:0.024)中上调。此外,在所有排斥组AAMR(PV:0.032),ACMR(PV:0.002),CAMR(PV:0.038)和CCMR(PV:0.013)中增加了MyD88表达,并且可以将它们与AUC的稳定移植物区分开(曲线下的面积分别为0.81,0.80,0.83和0.77。结论这些数据显示,肾组织中的MYD88基因上调可能具有诊断价值,PBMC中的TLR4 mRNA水平增加可能是暗示细胞介导的拒绝。因此,监测炎症信号传导基因的表达水平可能是可用于预测同种异体移植抑制的。

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