Dalton R S J, Webber J N, Pead P, Gibbs P J, Sadek S A, Howell W M
Wessex Renal and Transplant Unit, Queen Alexandra Hospital, Portsmouth, UK.
Transplant Proc. 2005 Mar;37(2):747-51. doi: 10.1016/j.transproceed.2004.12.097.
We sought to determine whether sequential changes in chemokine ligand/receptor gene expression in the early posttransplant period of human renal allografts can be detected in peripheral blood mononuclear cells (PBMCs) and whether any such changes are predictive of clinical events.
Blood samples from 106 renal transplant recipients and 29 donor nephrectomy patients were taken preoperatively and daily for 14 days. Within the study period 22 patients had biopsy-proven acute rejection. From each blood sample PBMCs were separated and gene expression levels for chemokines CCL3, CCL4, CCL5, CXCL10, and their receptors CCR1, CCR5, and CXCR3, were determined using real-time quantitative PCR.
Different gene expression patterns were seen between the rejector and nonrejector groups with decreases in CCL4 and CCR5 expression on days 6 to 8 and increases in CCR1 expression on days 9 and 10 posttransplant. With CXCL10, decreases in expression were seen in the nonrejector group but increases were seen in the rejector group posttransplant. With data aligned to time of rejection diagnosis, statistically significant increases, that preceded the clinical detection of acute rejection were seen in CCR1 and CXCL10 expression. Both their expression levels returned to pretransplant baseline values after successful antirejection therapy.
We have demonstrated that changes in chemokine receptor/ligand gene expression by sequential monitoring in PBMCs can be detected in the early posttransplant period. In particular, CCR1 and CXCL10, which showed increased expression prior to rejection and returned to baseline levels with antirejection therapy, may have potential use in immunomonitoring and as predictive factors of rejection prior to its clinical manifestation.
我们试图确定在人类肾移植术后早期，趋化因子配体/受体基因表达的序贯变化能否在外周血单个核细胞（PBMC）中被检测到，以及这些变化是否能预测临床事件。
对106例肾移植受者和29例供体肾切除患者在术前及术后14天每天采集血样。在研究期间，22例患者经活检证实发生急性排斥反应。从每份血样中分离出PBMC，使用实时定量PCR测定趋化因子CCL3、CCL4、CCL5、CXCL10及其受体CCR1、CCR5和CXCR3的基因表达水平。
在发生排斥反应和未发生排斥反应的两组之间观察到不同的基因表达模式，移植后第6至8天CCL4和CCR5表达降低，第9和10天CCR1表达增加。对于CXCL10，未发生排斥反应的组中表达降低，而发生排斥反应的组中移植后表达增加。将数据与排斥反应诊断时间对齐后，在急性排斥反应临床检测之前，CCR1和CXCL10表达出现统计学上的显著增加。在成功的抗排斥治疗后，它们的表达水平均恢复到移植前的基线值。
我们已经证明，通过对PBMC进行序贯监测，可以在移植术后早期检测到趋化因子受体/配体基因表达的变化。特别是CCR1和CXCL10，在排斥反应前表达增加，并在抗排斥治疗后恢复到基线水平，它们可能在免疫监测中具有潜在用途，并可作为排斥反应临床表现之前的预测因素。
