Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Nephrol Dial Transplant. 2010 Dec;25(12):4087-92. doi: 10.1093/ndt/gfq589. Epub 2010 Sep 27.
Experimental studies have shown potential for Toll-like receptor (TLR) profiling in renal allograft in predicting renal outcome after transplantation. Our goal was to determine if profiling of TLR1-10 and TLR-related genes could be used as a prognostic value for renal function and late clinical outcome after transplantation.
TLR1-10, CD14, MD-2 and negative regulators Toll-interacting protein (TOLLIP) and single immunoglobulin domain IL-1R-related receptor were analysed in 36 biopsies from renal transplant recipients with acute rejection (AR) and in 14 biopsies from renal transplant recipients without rejection (NR). Analysis was performed by multiplex ligation-dependent probe amplification. TLR (-related) genes were correlated to Banff'07 classification, cellular influx, response to conventional anti-rejection therapy, renal function 12 and 24 months after rejection and graft loss.
mRNA levels of most TLRs were significantly higher in acute rejection while TOLLIP mRNA level was decreased. mRNA levels of TLR1/2/4/7/8 were highly accurate in distinguishing AR from NR. TLR mRNA levels correlated to inflammatory parameters according to the Banff'07 classification and to cellular influx. Elevated mRNA level of TLR3 in acute rejection was independent from infiltrating leukocytes. TLR (-related) genes were not correlated with response to conventional anti-rejection therapy. Splice variant TLR4r3 was associated with poor renal function 24 months after transplantation, and TLR1 appeared to be associated with graft loss.
The elevated mRNA levels of several TLRs in association with reduced mRNA levels of TOLLIP in renal transplant biopsies of patients with acute rejection indicate a pro-inflammatory state, which may contribute to uncontrolled inflammation.
实验研究表明，Toll 样受体（TLR）谱分析在预测移植后肾功能方面具有潜力。我们的目标是确定 TLR1-10 和 TLR 相关基因的谱分析是否可作为移植后肾功能和晚期临床结果的预后价值。
在 36 例急性排斥反应（AR）肾移植受者活检标本和 14 例无排斥反应（NR）肾移植受者活检标本中分析 TLR1-10、CD14、MD-2 和负调节因子 Toll 相互作用蛋白（TOLLIP）和单免疫球蛋白域 IL-1R 相关受体。通过多重连接依赖性探针扩增进行分析。将 TLR（相关）基因与 Banff'07 分类、细胞内流、对常规抗排斥治疗的反应、排斥后 12 个月和 24 个月的肾功能以及移植物丢失相关联。
急性排斥反应中大多数 TLR 的 mRNA 水平显著升高，而 TOLLIP mRNA 水平降低。TLR1/2/4/7/8 的 mRNA 水平在区分 AR 与 NR 方面具有高度准确性。TLR mRNA 水平与 Banff'07 分类和细胞内流的炎症参数相关。急性排斥反应中 TLR3 的 mRNA 水平升高与浸润白细胞无关。TLR（相关）基因与常规抗排斥治疗的反应无关。剪接变体 TLR4r3 与移植后 24 个月肾功能不良相关，TLR1 似乎与移植物丢失相关。
在急性排斥反应肾移植受者活检标本中，几种 TLR 的 mRNA 水平升高，同时 TOLLIP 的 mRNA 水平降低，表明存在促炎状态，这可能导致炎症失控。
