肾移植受者HLA体液免疫致敏状态的监测及其临床意义

Surveillance of the humoral sensitization status in allogenic kidney transplantation recipients and its clinical significance

为探讨肾移植受者同种异体HLA抗原致敏后体液免疫状态与术后排斥反应及移植物存活率的相关性及其临床意义,应用One Lambda混合抗原板(LATM)通过ELISA筛查受者术前血清中的HLA-IgG抗体,对阳性血清进一步用抗原板(LAT1240和LAT1HDS)检测抗体阳性率及其特异性;并采用序列特异性引物聚合酶链反应(PCR-SSP)技术进行HLA基因分型。在1 297例肾移植受者中,HLA-IgG抗体阳性者165例,其中I类抗体阳性126例,II类抗体阳性90例,51例同时存在I类和II类HLA-IgG抗体,抗体阳性率>50%的高致敏受者94例。所有受者术后未发生超急性排斥反应,抗体阳性组受者的急性排斥发生率与阴性组受者比较,没有统计学差异。然而抗体阳性组受者移植物功能延迟恢复(DGF)的发生率显著高于阴性组受者(P<0.001)。抗体阳性组受者的1年、3年和5年移植肾存活率分别为95%、88%和80%;与抗体阴性组受者组比较无统计学差异。女性受者中抗体阳性率明显高于男性受者(P<0.001);再次移植受者中抗体阳性率显著高于初次移植受者(P<0.001)。抗体阳性组受者的供受者配型明显优于抗体阴性组受者。HLA-IgG抗体是反映受者体液免疫致敏状态的敏感指标,供受者间良好的HLA配型能显著降低排斥反应发生率和改善移植物存活。

To understanding the significance of the humoral sensitization of allograft rejection and the allograft survival, the anti-HLA Ⅰ and HLA Ⅱ antibodies in allogenic kidney transplantation recipients were minitored and their relationship with the clinical outcomes during 5 years period after operation was analyzed. At first, the sera of recipients were screened for anti- HLA IgG antibodies by ELISA with Lambda mixed antigen tray （LATM）, and the positive sera were further assayed with Lambda antigen trays （LAT1240 and LAT1HDS） to determine percentage of panel reactivity and the specificity of antibodies to HLA antigens . Genotyping of the HLA alleles was performed by PCR with sequence-specific primers （PCR-SSP）. It was found that, in 1 297 recipients, 1 132 of them was found to be anti-HLA negative, and 165 to be anti-HLA positive. Among the antibody-positive recipients, 126 cases were positive for HLA-I-IgG-antihodies, 90 cases belonged to the HLA-Ⅱ-positive recipents and 51 cases were positive both for HLA-I and HLA-Ⅱ-IgG antibodies. 94 cases were classified as the highly sensitized recipients, as their panel reactivity was over 50%. No hyperacute rejection was found in all recipients, and there was no significant difference in the incidence of developing acute rejections between anti-HLA-IgG positive and negative recipiemts （15.2% vs 12.9%, P〉0.05）. However, the incidence of developing the delayed graft function （DGF） in positive recipients was significantly higher than that in negative ones （33. 9% vs 11.9%, P〈0. 001）. The graft survival rates at 1, 3 and 5 years after kidney transplantation in positive and negative recipients were 95 %/ 97 %, 88 %/89 % and 80 %/85 % respectively, showing no statistical difference between these two groups of recipients at all these 3 time points（P〉0.05）. In addition, the tilers of the anti-HLA antibodies were significantly higher in female candidates than those in males （24.7 % vs 5.8%, P（ 0.001）, and the positive rate of anti-HLA antibodies in transplantation experienced candidates was dramatically higher than that in the primary candidates （33.8% vs 11.3%, P（0. 001）. In conclusion, it is evident that the level of anti-HLA-IgG antibodies can be used as a sensitive indicator to evaluate the humoral sensitization status of the allogenic kidney transplantation recipients in order to obtain a better HLA matching to reduce the rejection rate and to prolong survival of allogtafts.