Krichen H, Khazen D, Sfar I, Ben Abdallah T, Bardi R, Jendoubi-Ayed S, Makhlouf M, Abderrahim E, Aouadi H, Ayed K, Gorgi Y
Research Laboratory of Transplantation Immunopathology (LR01SP03), University Tunis El Manar, Department of Nephrology, Charles Nicolle Hospital, Tunis, Tunisia.
Transplant Proc. 2011 Mar;43(2):433-6. doi: 10.1016/j.transproceed.2011.01.029.
As chemokines and adhesion molecules play major roles in the process by which leukocytes are recruited from the bloodstream into sites of inflammation, genetic variations in the production or activity of molecules may influence susceptibility to acute rejection episodes. This study sought to determine the impact of recipient monocyte chemoattractant protein-1 (MCP-1), chemokine receptor (CCR2, CCR5), and adhesion molecule (ICAM-1, PECAM-1 and L/E selectin) polymorphisms on acute rejection after renal transplantation. We selected 169 healthy blood donors and 173 renal transplant recipients for analysis according to the presence or absence of graft rejection in the first 30 days after transplantation. Using molecular methods DNA was genotyped for 11 polymorphisms of these inflammatory molecules genes. Results were stratified by the incidence of rejection episodes and by human leukocyte antigen (HLA) mismatching. No association was detected between adhesion molecule polymorphisms and the incidence of acute rejection episodes. However, a significant risk of acute renal loss was observed among HLA-identical recipients who possessed the CCR2-64I allele (odds ratio 0.24, 95% confidence interval, 0.05 to 1.06; P=.035). In conclusion, the observed association of CCR2-64I with acute rejection episodes should be added to the spectrum of immunogenetic factors known to be involved in renal allograft rejection.
由于趋化因子和黏附分子在白细胞从血流中募集到炎症部位的过程中起主要作用,这些分子产生或活性的基因变异可能影响急性排斥反应的易感性。本研究旨在确定受体单核细胞趋化蛋白-1(MCP-1)、趋化因子受体(CCR2、CCR5)和黏附分子(ICAM-1、PECAM-1和L/E选择素)基因多态性对肾移植后急性排斥反应的影响。我们根据移植后前30天内是否发生移植排斥反应,选择了169名健康献血者和173名肾移植受者进行分析。采用分子方法对这些炎症分子基因的11种多态性进行基因分型。结果按排斥反应发生率和人类白细胞抗原(HLA)错配情况进行分层。未检测到黏附分子多态性与急性排斥反应发生率之间的关联。然而,在具有CCR2-64I等位基因的HLA相同的受者中,观察到急性肾丢失的显著风险(优势比0.24,95%置信区间,0.05至1.06;P=0.035)。总之,观察到的CCR2-64I与急性排斥反应的关联应纳入已知参与肾移植排斥反应的免疫遗传因素范围。