HLA氨基酸三维构象差异在非血缘造血干细胞移植中的作用分析

Role of HLA Protein Three-dimensional Conformation Difference in Unrelated Hematopoietic Stem Cell Transplantation

本研究探讨HLA氨基酸三维构象软件在评价不同HLA构象对造血干细胞移植预后的作用。回顾分析62例北京市道培医院单中心非血缘造血干细胞移植(30例HLA等位基因10/10全合和32例HLA等位基因9/10相合)。应用Histocheck和HLA-Matchmaker2个HLA抗原三维空间构象分析软件,分析其评分系统与移植后1年总生存率、急性GVHD和复发率的相关性。结果表明:①随着Histocheck软件的评分的增加,Ⅲ-Ⅳ度GVHD的发生率增加((0%增加到20%,p=0.25),但是高分组中仍有70%病例没有或只有轻度GVHD。对移植后的复发进行统计,除Histocheck分数偏高组(11-20)9例没有复发,其它组复发率差别不大(20%左右),(p=0.56)。②应用HLA-Matchmaker软件分析,随着供受者Eplet差异数目的增加,重度GVHD的发生率明显增加(0%增加到30%),无或轻度GVHD的发生率下降(p=0.019),但高分组中仍有60%没有或只有轻度GVHD,统计学有差异。差异数目偏高组(≥3)共10例均没有复发,偏低组(<3)复发率偏高(20%左右p=0.54)。结论:Histocheck和HLA-Matchmaker两个分析软件虽然对于HLA抗原构象差异的计算方法不同,但结果有很多的相近性。对于同一组供受者,两个给分系统与急性GVHD和复发的相关性类似,高分组中重度GVHD的比例增加,复发率下降,但相关性都不准确。HLA-Matchmaker软件的相关性略好于Histocheck。

This study was purposed to investigate the value of Histocheck and HLA-Matchmaker softwares in evaluating influence of HLA protein three dimensional conformation among individuals on outcome of unrelated donor hematopoietic stem cell transplantation（URHSCT）.Data of the HLA-A/B/C/DRB1/DQB1 genotypes from 62 cases of URHSCT（HLA-allele 10/10 match 30 cases,9/10 match 32 cases） were input into Histocheck and HLA-Matchmaker softwares respectively.The relationship between the software dissimilar scores and the 1 year overall survival（OS）,incidence of aGVHD of Ⅲ-Ⅳ grade and relapse rate was analyzed.The results showed that（1） with increase of the Histocheck scores,incidence of aGVHD of Ⅲ-Ⅳ increased from 0% to 20%（p=0.25）,while no or mild aGVHD occurred in 70% cases with the high scores.For the relapsed cases,there was no significant difference between the cases with low scores and with highest scores（relapse rate 20%） except that 9 cases had no relapse in the group with higher score（11-20）.（2） the analysis using HLA matchmaker software showed that incidence of aGVHD of Ⅲ-Ⅳ grade increased with the increase of numbers of mismatch Eplets,arranging from 0% to 30%,the incidence of moderate aGVHD reduced（p=0.019）,whereas 60% cases in highest scores group had moderate aGVHD.No relapse occurred in the group with higher scores（≥3）（n=10）,whereas high relapse rate appeared in the lower score group（20%,p=0.54）.It is concluded that the value of Histocheck and HLA-Mtchmaker software for analysing the outcome of URHSCT may be similar despite of different calculating methods;for the certain pair of recipient and donor,correlation of the two score systems with incidence of aGVHD and relapse rate is similar,but with less accuracy;The HLA Matchmaker software appears better than Histocheck software in terms of correlation.