儿童ABO血型不相容活体肝移植术后供者血型抗原不完全免疫耐受状态的研究

Clinical research of incomplete immune tolerance to donor specific blood group antigen in pediatric ABO incompatible living donor liver transplantation recipients

目的结合临床数据及文献分析儿童ABO血型不相容活体肝移植针对血型抗原低免疫应答状态的潜在免疫机制。方法回顾性收集首都医科大学附属北京友谊医院2013年6月至2020年12月期间施行的术后长期生存的儿童ABO血型不相容活体肝移植受者29例,受者血型均为O型,其中A型供者10例,B型供者19例。移植物类型包括左外侧叶26例,左半肝3例;肝移植手术中位年龄10月龄,中位体重为8.0 kg,中位随访时间41.9个月。连续监测移植术前及移植术后1、3、6、12、24、36个月受者体内针对供者血型相关抗体与供者血型非相关抗体滴度(IgG、IgM),并进行比较分析。对纳入受者进行程序性肝脏病理穿刺活检或事件性肝脏病理穿刺活检判断是否存在抗体介导排斥反应。结果受者移植术前及术后血型抗体(IgG、IgM),受者体内抗供者血型相关抗体滴度呈持续低水平状态,较体内非供者血型相关抗体滴度水平显著降低,差异有统计学意义(P<0.001)。对于纳入研究的29例受者,共有18例完成程序性肝脏病理活检,其中2例提示血管内皮C4d阳性;5例完成肝功能异常事件性肝脏病理活检,其中1例存在胆管内皮C4d阳性,肝脏病理活检未发现典型血型抗体介导抗原-抗体复合物介导级联免疫反应病理征象。结论儿童ABO血型不相容活体肝移植受者体内针对供者血型相关血型抗体为低水平表达,呈现为针对供者血型抗原的不完全免疫耐受状态。

Objective To explore the potential immune mechanism of pediatric ABOi-LDLT presenting low humoral immune response to donor specific blood group antigen.Methods From June 2013 to December 2020,clinical data were retrospectively reviewed for 29 patients of long-term surviving pediatric ABOi-LDLT.There were A to O ABOi-LDLT(n=10)and B to O ABOi-LDLT(n=19).Graft types included left lateral lobe(n=26)and left hemi-liver(n=3).The median age of liver transplantation was 10 months,the median weight 8.0 kg and the median follow-up time 41.9 months.The titers of donor specific blood group antibodies and non-donor specific blood group antibodies(IgG,IgM)were continuously monitored before transplantation and at 1,3,6,12,24,36 months post-transplantation.Protocol or event-based liver biopsy was performed to determine whether or not there was antibody-mediated rejection.Results The titer of donor specific blood group antibody in recipients was significantly lower than that of non-donor specific blood group antibody(P<0.001).Among 18 protocol liver pathological biopsies,two cases were C4d positive for vascular endothelium.Five abnormal event-based liver biopsies were completed and one was C4d positive in bile duct endothelium.No pathological sign of typical blood group antibody mediated antigen-antibody complex mediated cascade immune reaction was detected in liver pathological biopsy.Typical pathological signs of blood group antibody mediated rejection were absent in protocol liver biopsy.Conclusions Donor specific blood group antibody is expressed at a low level in pediatric ABOi-LDLT recipients.It presents as incomplete immune tolerance to donor specific blood group antigen.