肾移植后抗HLA和MICA抗体对移植肾慢性排斥反应的影响

Effect of HLA and MICA antibodies on chronic allograft rejection after renal transplantation

背景:体液免疫是影响移植肾长期存活的重要因素之一,抗HLA类抗体和抗MICA抗体在诱发慢性移植肾排斥反应中发挥了重要作用。目的:探讨肾移植受者血清抗HLA抗体及MICA抗体与术后移植肾慢性排斥反应及存活率的相关性及其临床意义。设计、时间及地点:病例对照分析,2001-01/2006-06南方医科大学附属珠江医院器官移植科。对象:选择接受肾移植后长期随访的患者60例,男32例,女28例,年龄25～73岁,平均(45.3±10.8)岁。将移植肾慢性排斥反应受者34例设为排斥组,同期手术移植肾功能仍稳定的26例受者设为对照组。方法:应用OneLambda混合抗原板通过酶联免疫吸附试验检测受者肾移植前血清中的抗HLA抗体,于2007-01/07月检测受者术后抗体情况,对阳性血清进一步用抗原板检测抗体阳性率及其特异性。采用免疫磁珠流式细胞仪液相芯片技术对肾移植者术前后进行抗MICA抗体测定;采用序列特异性引物聚合酶链反应技术进行HLA基因分型。主要观察指标:①肾移植患者手术前后抗HLA抗体滴度及特异性的动态变化。②受者术后抗MICA抗体合成情况。③移植肾功能。④移植受者及移植物的存活率。结果:在60例肾移植受者中,抗体阴性者27例,抗体阳性者33例,阳性率为55%,其中抗HLA抗体阳性12例,抗HLA和MICA抗体均阳性7例,抗MICA抗体阳性14例。慢性排斥组的抗HLA抗体阳性率显著高于移植肾功能稳定组(P<0.01);慢性排斥组和肾功能稳定组MICA抗体阳性受者分别为16例(47.1%)和5例(19.2%),两者比较具有显著性差异(P<0.05);抗体阳性患者血清肌酐明显高于抗体阴性者,其中抗HLA和MICA抗体均阳性者肌酐水平显著高于单一抗体阳性者(P<0.05)。结论:抗HLA抗体介导的体液性排斥反应在诱发慢性移植肾排斥中发挥了主要作用。同时,抗MICA抗体可与内皮细胞上表达的多态性MICA抗原作用,也可导致移植物的慢性损伤。

BACKGROUND： Humoral immunity is an important factor for long-term survival following renal transplantation. OBJECTIVE： To investigate the effect of anti-HLA and anti-MICA antibodies on chronic allograft rejection and survival rate. DESIGN, TIME AND SETTING： A case-control experiment was performed at Department of Organ Transplantation, Affiliated Zhujiang Hospital, Southern Medical University, from January 2001 to June 2006. PARTICIPANTS： Sixty patients who received renal transplantation and a long time follow-up were involved in this experiment. The patients with chronic allograft rejection were assigned into chronic allograft rejection group （n=-34）, and the other patients with good renal function were assigned into control group （n=-26）. METHODS： Serum anti-HLA antibodies before transplantation were detected by enzyme-linked-immuno-sorbent-assay（ELISA） with One Lambda antigen tray （LAT）. After operation, anti-HLA antibodies in serum were detected from January to July 2007. If the anti-HLA antibody in serum was positive, the positive rates and their specificities would be detected by LAT. MICA antibodies in serum were detected by Luminex flow cytometric technology. HLA genotyping was detected by PCR-SSP. MAIN OUTCOME MEASURES： （1）Dynamic changes in titer and specificities of anti-HLA antibodies in serum before and after transplantation; （2） The synthesis of anti-MICA antibodies after transplantation; （3） Renal function of the patients; （4） Survival rates of the patients and grafts. RESULTS： Twenty-seven of sixty patients were antibodies negative, and the other thirty-three ones were antibodies positive. The positive antibodies rate was 55%. Twelve patients were anti-HLA antibodies positive, fourteen patients were anti-MICA antibodies positive, seven patients were both anti-HLA and anti-MiCA antibodies positive. The positive anti-HLA antibodies rate of patients in the chronic ailograft rejection group was significantly higher than that in the control group （P 〈 0.01）. The positive anti-MICA antibodies rates of patients in the chronic allograft rejection and control groups were 47.1% and 19.2%, respectively. The positive rate of patients in the chronic allograft rejection group was significantly higher than that in the control group （P 〈 0.05）. The serum creatine level of the patients who were antibodies positive was significantly higher than that of patients who were antibodies negative （P 〈 0.05）. The serum creatine levels of the patients who were both anti-HLA and anti-MICA antibodies positive were significant higher than that in patients who were only anti-HLA or anti-MICA antibodies positive（P 〈 0.05）. CONCLUSION： Anti-HLA antibody-mediated humoral immunity plays a key role in chronic allograft rejection of renal transplantation. Meanwhile, anti-MICA antibody might respond with polymorphic MICA antigens expressed by endothelial cells in allografts and lead to chronic rejection.