HLA配型及受者PRA情况对致敏患者肾移植后2年疗效的影响

The Impact of HLA Matching and Recipients' PRA on Two-year Outcome in Presensitized Renal Allograft Recipients

目的探讨HLA配型及受者PRA情况对致敏患者肾移植后2年疗效的影响。方法测定73例预致敏肾移植受体体内抗-HLA抗体的致敏程度及抗体特异性,并与81例未致敏受体进行比较,受体以及相应供体的HLA基因型均采用序列特异性引物PCR(PCR-SSP)进行分析,分析了影响早期移植结果的因素(移植物的2年排斥率和生存率),包括HLA错配、群体反应性抗体种类及特异性,以及供者的靶抗原。结果预致敏受者比未致敏受体的2年预后差(移植排斥率P=0.019,生存率P=0.01),无论是以6抗原匹配(AgM)或氨基酸残基匹配(Res M)为标准,对预致敏受体而言,HLA错配数对移植物排斥率,或者移植物存活率均无显著影响。与对照组相比,同时产生PRA-Ⅰ、PRA-Ⅱ两种抗体的移植物受体的两年预后更差(移植排斥率P=0.001,生存率P=0.002)。PRA峰值≥50%的组及其分组,移植时PRA值大于50%,他们的两年预后明显比对照组差(移植排斥率P_1=0.025,P_2=0.001,生存率P=0.043,P=0.024)。移植时靶抗原阳性组及其分组,HLA-Ⅰ阳性的组,其移植物排斥率明显高于对照组(P=0.001,P=0.001),高于靶抗原阴性组(P=0.003,P=0.001),高于靶抗原峰值阳性但移植时靶抗原阴性的受体(P=0.024,P=0.002)。靶抗原阳性组还有HLA-Ⅰ靶抗原阳性组的两年生存率明显低于对照组(P=0.012,P=0.001),靶抗原未明组的两年移植结果与靶抗原阳性组类似。经过血浆滤过及免疫吸附的预致敏受者(PRA处理组)的两年移植结果优于对照组,但无统计学意义。但未经处理的PRA预致敏受者的结果与对照组是不同的(排斥率P=0.004,生存率P=0.005),3例HLA-Ⅰ靶抗原阳性、按照氨基酸残基标准无错配的受体发生超急性排斥,1例PRA-Ⅱ阳性(靶抗原未知)的受者发生超急性排斥反应,PRA-Ⅱ靶抗原阳性的8例受者未见超急性期排斥反应。结论移植前PRA预处理可以改善预致敏受体肾移植后的预后,避免抗原阳性供者仍然是预防超急性排斥反应和早期排斥反应的基本措施。

Objective To evaluate the impact of HLA matching and recipients' PRA on two - year outcome in presensitized renal allograft recipients.Methods We determined the percentage of panel reactivity and specificity of anti -HLA immunoglobulin(Ig) G antibodies in 73 presensitized renal allograft recipients compared with 81 unsensitized recipients(control group).HLA genotyping of both recipients and corresponding donors was performed by PCR with sequence - specific primers(PCR - SSP).We analyzed the factors influencing the early graft outcome(two -year rejection rates and survival rates of the grafts),including HLA mismatching,class and degree of panel reactivity,and target antigen of donors.Results Presensitized recipients had a worse two - year outcome than unsensitized recipients(P =0.019 for rejection rate,P =0.01 for survival rate).The difference in number of HLA - mismatched alleles with either 6 - antigen matching(Ag M) standard or amino acid residue matching(Res M) standard was not significant between the rejection and non - rejection groups of presensitized recipients or between the graft survival group and graft loss group.Compared with the control group,recipients with both PRA -Ⅰand PRA -Ⅱhad a significantly worse two - year outcome(P =0.001 for rejection rate,P = 0.002 for survival rate).The two - year outcome of the peak PRA 3= 50%group and its subgroup,at - transplant PRA≥50%group,were significantly worse compared with the control group(P= 0.025 and P =0.001 for rejection rate,P =0.043 and P -0.024 for survival rate).The rejection rates of the at - transplant target antigen positive group and its subgroup,HLA -Ⅰtarget antigen positive group,were significantly higher than the control group(P = 0.001 and P = 0.001),target antigen negative group(P = 0.003 and P = 0.001),and peak target antigen positive with negative at - transplant target antigen group(P = 0.024 and P = 0.002).Two - year graft survival rates of the target antigen positive group and HLA -1 target antigen positive group were significantly lower than the control group(P =0.012 and P =0.001).The two - year outcome of target antigen unknown group was similar to that of the target antigen positive group.Presensitized recipients with pre - transplant plasmapheresis or immunoadsorption(PRA prepared group) had a better but non - significant two - year outcome than the control group.However,the PRA unprepared presensitized recipients was different to the control group(P =0.004 for rejection rate and P=0.005 for survival rate).Hyperacute rejection(HR) occurred in three recipients with positive HLA -Ⅰtarget antigen and without mismatch according to Res M and in one case with positive PRA -Ⅱ(for an unknown target antigen).No HR occurred in eight cases with positive HLA -Ⅱtarget antigens.Conclusions Pre - transplant PRA preparations might improve the access of presensitized patients to renal donors.Avoiding antigen - positive donors remains a fundamental measure in preventing HR and early rejections.