HLA测序技术在非亲缘性脐血移植应用价值探讨

1998年6月至2004年7月，广州脐血库向国内21家移植中心54例患者提供了非亲缘性异基因脐血。为了探讨非亲缘性脐血移植供／受者HLA等位基因及其亚型与脐血移植GVHD发生率的关系，对54例非亲缘性脐血移植病例中，半年后有反馈随访资料的48例，利用盐析或柱提法提取移植的非亲缘性脐血的DNA及移植病例的全血DNA，采用HLA—SBT方法分别对HLA—A、B、DRB1位点进行了高分辨分型，并与我库脐血收集常规采用的HLA—SSP（HLA—Sequencing specific primers）低分辨结果进行了比较分析。结果发现，HLA不合位点不多于2个和HLA不合位点不少于3个的病例GVHD的发生率具有统计学显著性差异（P〈0．05）。在对HLA—A、B、DRB1等位基因高分辨单因素分型结果中，HLA—B和HLA-DRB1等位基因匹配全相合的病例GVHD发生率显著低于不完全相合病例GVHD的发生率（P=0．000，P=0．005）。结论：PCR—SBT技术在非亲缘性脐血移植HLA配型方面具有重要的临床应用价值。

Clinical Application of HLA Sequencing in Unrelated Umbilical Cord Blood Transplantation

From June 1998 to July 2004, Guangzhou umbilical cord blood bank provided unrelated umbilical cord blood for 54 patients to more than 21 transplantation centers. HLA sequencing-based typing (SBT) was used to re-analyze the results of HLA antigens and alleles so as to investigate the relationship between HLA alleles and GVHD. The information about 48 out of 54 patients was obtained after 6 months of follow up. SBT was used to identify HLA-A, B, DRB1 alleles in 48 patients received the unrelated umbilical cord blood units, and the obtained results were compared with the results of HLA-SSP Low Resolution Typing. The results showed that the difference of GVHD incidence between less than 2 mismatched HLA sites and less than 3 sites was statistically significant (P<0.05). In the results from single factor analysis and high-resolution typing of HLA-A,B and DRB1 alleles, the mismatch between HLA-B and HLA-DRB1 alleles was found to be a significant factor for the occurence of GVHD. It is concluded that SBT plays an important role in umbilical cord blood transplantation, and the incidence of GVHD is higher in the transplantation with HLA-DRB1 alleles mismatching.