Intrarenal cytokine and chemokine gene expression and kidney graft outcome
Intrarenal cytokine and chemokine gene expression and kidney graft outcome
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DOI：
10.1159/000105134
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发表时间：
2007-01-01
影响因子：
2.8
通讯作者：
Viklicky, Ondrej
中科院分区：
文献类型：
--
作者：
Hribova, Petra;Lacha, Jiri;Viklicky, Ondrej
目的：促炎性细胞因子被认为在各种移植肾疾病中起重要作用，导致间质纤维化和肾小管萎缩，这在病例活检中经常发现。为了探讨各种细胞因子和趋化因子在长期移植物结局中的作用，评估了它们在肾移植活检组织中的基因转录模式。研究方法：采用实时荧光定量RT-PCR技术检测74例肾移植受者移植肾内细胞因子和趋化因子mRNA的表达，并将检测结果与移植肾的组织学、临床指标及移植肾的远期预后进行相关性分析。结果如下：我们观察到与对照组相比，慢性移植物肾病（CAN）患者的IL-10（p < 0.001）、TGF-β（1）、IL- 6、MCP-1、RANTES（p < 0.01）和TNF-α（p < 0.05）mRNA表达上调。IL-6（p < 0.001）、IL-10（p <0.01）、TNF-α、MCP-1（p < 0.05）的mRNA表达与尿蛋白量呈正相关。CAN患者肾内MCP-1的上调增加了未来42个月内移植物衰竭的风险（OR 5.1，p < 0.05）。Kaplan-Meier生存分析显示，蛋白尿和移植肾内TGF-β 1和MCP-1的高表达预示着肾移植预后不良。结论：肾内促炎基因的表达模式可能会区分早期移植失败风险较高的患者。版权所有（c）2007 S. Karger AG，巴塞尔。
Aims: Proinflammatory cytokines are thought to play an important role in various kidney graft diseases resulting in interstitial fibrosis and tubular atrophy frequently found in case biopsies. To explore the role of various cytokines and chemokines in the long-term graft outcome, the transcription patterns of their genes in kidney allograft biopsies were evaluated. Methods: The real-time RT-PCR was used to identify intragraft mRNA expression of cytokines and chemokines in 74 kidney graft recipients and the results were correlated with histological and clinical parameters and long-term graft outcome. Results: We observed up-regulated IL-10 (p < 0.001), TGF-beta(1), IL- 6, MCP-1, RANTES (p < 0.01) and TNF-alpha (p < 0.05) mRNA expression in patients with chronic allograft nephropathy ( CAN) as compared to controls. There were positive correlations between the mRNA expression of IL-6 (p < 0.001), IL-10 (p < 0.01), TNF-alpha, MCP-1 (p < 0.05) and the proteinuria. The up- regulation of intrarenal MCP-1 in patients with CAN increased the risk for the graft failure within the next 42 months (OR 5.1, p < 0.05). Kaplan-Meier survival analysis revealed that proteinuria and higher intragraft expression of TGF-beta(1) and MCP-1 predict a poor kidney graft outcome. Conclusion: Expression patterns of intrarenal pro-inflammatory genes might discriminate patients at a higher risk for the earlier allograft failure. Copyright (c) 2007 S. Karger AG, Basel.