HLA-A和HLA-B与HLA-DRB1基因低分辨相合的无关供／受者对HLA高分辨水平匹配性分析

Analysis of high-resolution human leukocyte antigen matching status for the unrelated donor-receipt pairs matched at low-resolution for HLA-A, HLA-B and HLA-DRBI

目的分析探讨HLA-A、HLA-B和HLA-DRBl基因低分辨相合无关供／受者对与HLA高分辨水平匹配的比例和特点。方法对318份HLA-A、B和DRBl基因低分辨相合的无关供／受者对标本进行HLA测序分型，从高分辨水平统计和分析HLA各基因座匹配的比例和特点，以及HLA系统中6个等位基因（HLA-A、HIA-B和HLA-DRB1位点）、8个等位基因（HLA-A、HLA-B、HLA-Cw和HIJA．DRB1位点）、10个等位基因（HLA-A、HLA—B、HIJA-Cw、HLA-DRB1和HLA-DQB1位点）的匹配性。结果单个HLA位点完全相合的比例为HLA-B[79．9％（254／318）]〉HIJA．DRB1[64．8％（206／318）]〉HLA-DQB1[62．3％（134／215）]=HLA-A[62．3％（198／318）]〉HLA-Cw[55．3％（119／215）]。6个等位基因完全相合的比例为36．2％（115／318），8个等位基因完全相合的比例下降为21．9％（47／215），10个等位基因完全相合的比例为20．5％（44／215）。在76份HLA-A、HIJA-B和HLA-DRBl等位基因6／6相合的样本中，等位基因8／8相合及10／10相合的比例分别为63．2％（48／76）和57．9％（44／76）；但其中1～2个HLA-Cw等位基因不相合的比例为36．8％（28／76），且主要为抗原水平不相合。结论实现HLA-A、HLA-B、HLA-DRBI的高分辨分型数据入库虽有助于提高无关供／受者对与HLA高分辨配型检索的成功率，但HLA-Cw抗原水平的不相合不能被忽视，建议将HLA-Cw基因分型纳入骨髓库骨髓志愿捐献者HLA入库数据的常规检测。

Objective To analyze and evaluate the high-resolution HLA matching status for the unrelated donor-receipt pairs who were matched at low-resolution for HLA-A, HLA-B and HLA- DRB1. Methods A total of 318 samples from Chinese Marrow Donor Program （CMDP） unrelated donor- receipt pairs matched at low-resolution for HLA-A, HLA-B and HLA-DRB1 were subjected to HLA sequence-based typing （SBT）. HLA matching status at each locus, as well as 6 alleles matching status for HLA-A, HLA-B and HLA-DRB1, 8 alleles matching status for HLA-A, HLA-B, HLA-Cw and HLA-DRB1 and 10 alleles matching status for HLA-A, HLA-B, HLA-Cw, HLA-DRB1 and HLA-DQB1 were analyzed. Results The ratio for high-resolution HLA comprehensive matching at each locus were ranked as ： HLA-B[79.9% （254/318） ] 〉 HLA-DRB1 [ 64. 8% （ 206/318 ） ] 〉 HLA-DQB1 [ 62. 3% （ 134/215 ） ] = HLA-A[62. 3% （198/318） ]〉 HLA-Cw[55.3% （119/215） ]. The ratio for HLA comprehensive matching at 6 alleles, 8 alleles and 10 alleles were 36. 2% （ 115/318）, 21.9% （47/215） and 20. 5% （44/215）, respectively. In the 76 unrelated donor-receipt pairs matching at high-resolution for HLA-A, HLA-B and HLA-DRB1, the ratio for donor-receipt pair allele full matching at 8/8 and 10/10 were 63.2% （48/76） and 57.9% （44/76） , respectively. However, 36. 8% （28/76） of them were found to carry single or two HLA- Cw alleles mismatching and predominately showed HLA-Cw antigen level mismatching. Conclusions HLA-A, HLA-B and HLA-DRB1 high-resolution genotyping for unrelated marrow donor will help improving thepercentage of HLA allele full matching for unrelated donor-receipt pairs. However, HLA-Cw mismatching at antigen level could no longer be ignored. The results indicated that HLA-Cw genotyping should be incorporated into future CMDP unrelated marrow donor routine HLA test.