血小板输注无效患者HLA等位基因特异性抗体及其表位的分析

Analysis of HLA allele-specific antibodies and Eplets in patients with platelet transfusion refractoriness

目的分析血小板输注无效(PTR)患者中HLA等位基因特异性抗体的特异性和表位情况。方法采用PCR-SBT方法检测患者HLA-A、B基因型,Luminex单抗原微珠包被法检测患者血清中HLA-Ⅰ类抗体。采用HLA比对软件寻找等位基因特异性抗体存在的差异氨基酸,HLA Eplet数据库分析注册表位。结果在82例PTR患者中发现12例患者存在HLA等位基因特异性抗体。经序列比对,共发现了19E>19K、166D>116E、167G>167W等18个差异氨基酸。在这些差异氨基酸中,检索到19E>19K、95I>95L、113YD>113HD等16个注册表位,另有166DG>166EW、70Q>70H、67S>67Y、94I>94T、82LR>82RG、211G>211A可能为尚未注册的新表位。A11、A24、B15、B27、B38等抗原可以进一步细分为HLA窄特异性抗原。结论发现PTR患者存在HLA等位基因特异性抗体,提示PTR的HLA配合性输注中宜对这类患者和血小板捐献者进行HLA-A、-B位点高分辨分型。

Objective To analyze the specificity and Eplets of HLA allele-specific antibody in patients with platelet transfusion refractoriness(PTR).Methods HLA-A and B genotypes were detected by PCR-SBT,and HLA-Ⅰantibodies in patients'serum were detected by Luminex single antigen beads coating method.IPD-IMGT/HLA Database was used to find the differential amino acids of allele-specific antibodies,and HLA Eplet database was used to analyze the registry Eplets.Results HLA allele-specific antibodies were found in 12 out of 82 patients with PTR.After sequence alignment,a total of 18 differenti-al amino acids were found,such as 19E>19K,166D>116E,167G>167W and so on.Among these differential amino acids,16 registry Eplets were retrieved such as 19E>19K,95I>95L,113YD>113HD and so on.The amino acid substitution of 166DG>166EW,70Q>70H,67S>67Y,94I>94T,82LR>82RG,and 211G>211A may form new Eplets that have not been registered.The antigens of A11,A24,B15,B27 and B38 can be further subdivided into HLA narrow specific antigens.Conclusion It was found that there were HLA allele-specific antibodies in patients with PTR,suggesting that high-resolution typing of HLAA,B should be carried out for these patients and platelet donors in HLA compatible transfusion of PTR.