HLA-A、-B功能表位错配对血液病患者血小板输注效果的影响分析

Effect of HLA-A,-B functional epitope mismatch on platelet transfusions in patients with hematological diseases

目的探究HLA抗原(human leukocyte antigen,HLA)功能表位错配(epitope mismatch,EM)对血液病患者血小板输注有效性的影响。方法对血小板供者和2021年6月—2023年6月间申请血小板血清学交叉配型和HLA基因配型的血液病患者,用PCR-SBT法进行HLA基因分型,HLA基因配型是基于CREG的原则为患者选择供者。对患者临床血小板输注资料进行回顾性分析,使用HLA Matchmaker 4.0软件分析供体-受体HLA EM信息,并从国际HLA表位注册网站(www.Epregistry.com.br)中查询相关HLA功能表位(Eplets)的表达量、基因分布等信息。评价HLA EM对血小板输注效果的影响。结果血液病患者血小板的输注有效性与患者性别、年龄无关,而与患者的血小板配型策略相关。当HLA EM总数在20以下时,供受者HLA EM总数越低的分组,其血小板输注有效率越高(χ^(2)=19.311,P=0.001),24 h血小板计数(Plt)增量校正值(CCI)平均数也越高(F=7.737,P<0.001)。供受者HLA EM总数与24 h CCI实际值呈负相关(Rho=-0.322,P<0.001)。进一步统计分析发现17个与血小板的输注有效性有关的Eplets,其基因位点分布可能是HLA-A(17.6%)或-B位点(64.7%)独有,或者是HLA-A和-B位点共享(17.6%);且其表达量可能是高表达(58.8%),或者是中等表达(41.2%)。结论HLA EM的总数是影响血小板输注有效性的重要因素;发现若干与血小板的输注有效性相关的HLA Eplets。

Objective To investigate the impact of human leukocyte antigen(HLA)functional epitope mismatch(EM)on the efficacy of platelet transfusion in patients with hematological diseases.Methods HLA genotyping was performed on platelet donors and patients with hematological diseases who applied for platelet serological cross-matching and HLA antigen matching from June 2021 to June 2023 by PCR-SBT method.HLA platelet matching was based on the principle of CREG to select donors for patients.HLA Matchmaker 4.0 software was used to analyze donor-recipient HLA EM information.The expression level and gene distribution of related HLA functional epitope(Eplet)were searched from the international HLA Epitope registry website(www.Epregistry.com.br).Retrospective analysis was conducted on clinical platelet transfusion data to evaluate the impact of HLA EM on platelet transfusion effectiveness.Results Platelet transfusion efficacy showed no correlation with gender and age,but it was associated with platelet matching strategy.When the total number of HLA EMs was less than 20,a lower total number of donor-recipient HLA EMs resulted in higher platelet transfusion efficiency(χ^(2)=19.311,P=0.001)and higher average value of 24 h corrected count increment(CCI)(F=7.737,P<0.001).The total number of donor-recipient HLA EMs had negative correlation with actual 24 h CCI(Rho=-0.322,P<0.001).Further statistical analysis revealed that 17 Eplets were related to the effectiveness of platelet transfusion.The locus distribution of 17 Eplets might be unique to HLA-A(17.6%)or-B(64.7%)or shared between HLA-A and-B(17.6%),and its expression may be high(58.8%)or intermediate(41.2%).Conclusion The total number of donor-recipient HLA EMs is a crucial factor influencing platelet transfusion effectiveness,and several HLA Eplets associated with this effectiveness have been identified.