肾移植患者抗人类白细胞抗体配型与术后急性排斥反应及移植肾存活的关系

背景:群体反应性抗体可介导超急性排斥反应,导致群体反应性抗体阳性致敏患者肾移植成功率和移植物存活率均低于非致敏患者.目的:根据人类白细胞抗原交叉反应组配型标准为群体反应性抗体阳性致敏肾移植患者选配合适供者,观察移植后急性排斥反?发生率及移植肾存活情况.设计:病例观察.单位:南方医科大学珠江医院.对象:选择1997-01/2003-12在南方医科大学珠江医院器官移植科施行肾移植136例群体反应性抗体阳性的致敏受者,男41例,女95例,年龄(45±9)岁.初次肾移植115例,2次移植18例,3次移植2例,4次移植1例.所有受试对象均对检测项目知情同意,实验经过医院伦理委员会批准.LAT莱姆德抗原板和LAT-Mix混合抗原板购自美国One Lambda公司.SMT72R抗人类白细胞抗原-1类单克隆抗体湿板和人类白细胞抗原-Ⅱ类DNA分型试剂购自美国One Lambda公司.方法:以酶联免疫吸附试验动态监测患者手术前后IgG型抗人类白细胞抗原抗体水平及其特异性.应用抗人类白细胞抗原-Ⅰ类单克隆抗体湿板进行供、受者人类白细胞抗原-Ⅰ类抗原分型,微量序列特异性引物法进行供、受者人类白细胞抗原-Ⅱ类基因分型,根据美国器官共享网制定的人类白细胞抗原交叉反应组配型标准和Ⅱ类抗原可接受性错配原则进行供、受者选配.评估抗原交叉反应组配型原则下患者移植术后急性排斥反应发生率及移植肾1,3,5年存活率进行评价.主要观察指标:①致敏患者手术前后抗人类白细胞抗原抗体水甲及特异性.②供受者人类白细胞抗原组织配型.③肾移植术后急性排斥反应发生率及移植肾存活率.结果:纳入136例PRA阳性致敏患者均进入结果分析,无脱落者.①致敏患者中104例存在抗人类白细胞抗原-Ⅰ类IgG抗体,76例存在抗人类白细胞抗原-Ⅱ类IgG抗体,44例同时存在抗人类白细胞抗原-Ⅰ类和Ⅱ类IgG抗体.②按照传统人类白细胞抗原配型标准供、受者人类白细胞抗原0,1,2,3,4个抗原错配者分别为7,26,47,39和17例;按照人类白细胞抗原交叉反应组配型标准供、受者人类白细胞抗原抗原0,1,2,3,4个抗原错配者分别为31,53,36,16和0例.③按人类白细胞抗原交叉反应组配型原则,人类白细胞抗原无错配者的急性排斥反应发生率明显低于2个和3个抗原错配者,差异有统计学意义(P<0.05),人类白细胞抗原无错配者移植肾1,3,5年存活率高于2个和3个抗原错配者,差异有统计学意义(P<0.05).结论:①人类白细胞抗原交叉反应组配型标准能提高肾移植供受者的相配率.②良好的人类白细胞抗原配型可降低肾移植术后急性排斥反应的发生率,提高移植肾的存活率.

Correlation of human leucocyte antigen matching to acute rejection and allograft survival after renal allograft

BACKGROUND: Panel reactive antibody (PRA) can mediate hyperacute rejection, and lead to decrease in success rate of transplantation and survival rate of renal graft in highly sensitized recipients compared to non-sensitized recipients.OBJECTIVE: According to human leucocyte antigen (HLA) cross-matching standards to select suitable donors for sensitized recipients and to evaluate the incidence of acute rejection and survival rate of renal allografts.DESIGN: Case observation.SETTING: Zhujiang Hospital of Southern Medical University.PARTICIPANTS: 136 sensitized recipients with positive PRA underwent renal transplantation in Department of Organ Transplantation, Zhujiang Hospital of Southern Medical University between January 1997 and December 2003 were selected, including 41 males and 95 females, aged (45±9) years. Recipients of first, second, third, and fourth transplant were 115, 18, 2 and 1 case, respectively. The informed consent was obtained from all patients. The protocol was approved by Hospital Ethics Committee. Lambda antigen tray (LAT) and LAT-Mix were purchased from One Lambda, Inc, USA. Special monoclonal tray -Asian HLA class Ⅰ (SMT72R) and Micro SSP Generic HLA Class Ⅱ (DRB/DQB) were also purchased from One Lambda, Inc, USA.METHODS: Pre-operative PRA levels and specificity of recipients were detected by ELISA test with Lambda antigen tray (LAT). Donor and recipient HLA class Ⅰ typing was performed with special tray - Asian HLA class Ⅰ (SMT72R), and HLA class Ⅱ gene typing with Micro SSP Generic HLA Class Ⅱ (DRB/DQB) (Micro-SSP). HLA-matching between donor and recipient was performed according to HLA cross-reactive group (CREG) standards by UNOS and class Ⅱ antigen permissible mismatch. The incidence of acute rejection and survival rate of renal allografts were evaluated within 1, 3 and 5 years.MAIN OUTCOME MEASURES: ①PRA levels and specificity of sensitized recipients before and after transplantation; ②HLA-matching between donor and recipient; ③Incidence of acute rejection and survival rate of renal allografts after transplantation.RESULTS: 136 PRA positive sensitized recipients were all included in final analysis. ① There were 104 recipients with anti-HLA class Ⅰ IgG antibody, 76 with anti-HLA class Ⅱ IgG antibody, and 44 with both anti-HLA class Ⅰ and Ⅱ IgG antibodies in 136 recipients. ②The number of cases of 0, 1, 2, 3, and 4 mismatch (MM) was 7, 26, 47, 39 and 17, respectively by the standard of conventional HLA antigen matching; However, the number of the recipients with 0, 1, 2, 3, and 4MM was 31, 53, 36, 16, and 0, respectively according to the principle of HLA CREG matching. ③By the principle of HLA CREG matching, rates of acute rejection in sensitized recipients with 2MM and 3MM HLA-CREG were significantly higher than those with 0MM (P < 0.05). Renal allograft survival rate in sensitized recipients with 0MM was significantly higher than those with 2MM and 3MM (P < 0.05).CONCLUSION: ①HLA CREG matching can significantly improve the ratio of well-matched. ② Good HLA matching can reduce the incidence of acute rejection in sensitized recipients and increase the survival rate of renal grafts.