T细胞表位模型和表达模型对非亲缘造血干细胞移植供受者HLA-DPB1基因错配风险的预测功能评估  

Risk prediction and function evaluation by T-cell epitope model and expression model of HLA-DPB1 mismatching in unrelated-donor hematopoietic stem cell transplantations

作　　者：齐珺[1] 王天菊[1] 王满妮[1] 尚利侠 陈乐 王小芳[1] 李昱辉 徐华[1] 马超锋 Qi Jun;Wang Tianju;Wang Manni;Shang Lixia;Chen Le;Wang Xiaofang;Li Yuhui;Xu Hua;Ma Chaofeng(Blood Center of Shaanxi Province,Institute of Xi′an Blood Bank,Xi′an 710061,China)

机构地区：[1]陕西省血液中心,西安710061

出　　处：《中华医学杂志》2024年第11期850-856,共7页National Medical Journal of China

基　　金：中国输血协会威高科研基金(CSBT-WG-2017-06);陕西省重点研发计划一般项目(2022SF-098)

摘　　要：目的评估T细胞表位(TCE)模型和表达模型对人类白细胞抗原(HLA)相合非亲缘造血干细胞移植(MUD-HSCT)供受者HLA-DPB1基因错配风险的预测功能。方法回顾性分析2016至2019年陕西省血液中心进行HLA高分辨分型确认的MUD-HSCT供受者364例(182对)。182例受者中,男121例,女61例,年龄(26.3±14.2)岁;182例供者中,男148例,女34例,年龄(33.7±7.5)岁。应用聚合酶链反应-测序分型(PCR-SBT)、下一代测序(NGS)技术和基于LABScan^(■)3D平台的聚合酶链反应-序列特异寡核苷酸探针技术(PCR-SSO)等进行HLA-A、B、C、DRB1、DQB1、DPB1基因高分辨分型,采用PCR-SBT进行单核苷酸多态性(SNP)分型,运用TCE模型和表达模型评估MUD-HSCT供受者HLA-DPB1基因错配模式和急性移植物抗宿主病(aGVHD)风险。结果检出26种HLA-DPB1等位基因及其3′-UTR rs9277534 SNP基因型,发现并正式命名2个新等位基因HLA-DPB1^(*)1052∶01和HLA-DPB1^(*)1119∶01。HLA-DPB1基因总错配率达90.66%(165/182),TCE模型允许错配占47.80%(87/182),不允许错配占42.86%(78/182);移植物抗宿主(GvH)方向的不允许错配为13.73%(25/182),宿主抗移植物(HvG)方向的不允许错配为29.12%(53/182)。TCE模型中共有73对供受者符合表达模型评估标准,其中TCE允许错配组的受者DP5错配占34.25%(25/73),根据表达模型预测其移植后aGVHD风险为高风险;TCE不允许错配组的受者DP2错配占6.85%(5/73),受者DP5错配占10.86%(8/73),均被预测为aGVHD高风险。两种模型之间的整体一致性为27.27%,不一致性为16.97%。结论TCE模型和表达模型是预测MUD-HSCT供受者HLA-DPB1基因错配风险的有效工具,综合应用两种模型有助于移植风险分层评估。Objective To evaluate the risk prediction and assessment function of HLA-DPB1 T-cell epitope(TCE)model and expression model in human leukocyte antigen(HLA)-matched unrelated hematopoietic stem cell transplantation(MUD-HSCT)with HLA-DPB1 mismatching.Methods A total of 364(182 pairs)potential MUD-HSCT donors and recipients confirmed by HLA high-resolution typing in Shaanxi Blood Center from 2016 to 2019 were analyzed retrospectively.Of the 182 recipients,there were 121 males and 61 females with an average age of(26.3±14.2)years.Of the 182 donors,there were 148 males and 34 females with an average age of(33.7±7.5)years.Polymerase chain reaction-sequence-based typing(PCR-SBT),next-generation sequencing(NGS)and polymerase chain reaction-sequence specific oligonucleotide probe(PCR-SSO)based on LABScan^(■)3D platform were used for high-resolution typing of HLA-A,B,C,DRB1,DQB1,DPB1 gene,and PCR-SBT was used for single nucleotide polymorphism(SNP)typing.TCE model and expression model were used to predict and evaluate the HLA-DPB1 mismatch pattern and acute graft-versus-host-disease(aGVHD)risk.Results A total of 26 HLA-DPB1 alleles and their 3′-UTR rs9277534 SNP genotypes were detected in this study population,and two new alleles HLA-DPB1^(*)1052∶01 and HLA-DPB1^(*)1119∶01 were found and officially named.The overall mismatch rate of HLA-DPB1 in MUD-HSCT donors and recipients was 90.66%(165/182).In TCE model,the HLA-DPB1 mismatch rates of permissible mismatch(PM)and non-permissible mismatch(non-PM)were 47.80%(87/182)and 42.86%(78/182),respectively.The non-PM in GvH direction was 13.73%(25/182),and which in HvG direction was 29.12%(53/182).A total of 73 pairs of donors and recipients in TCE model met the evaluation criteria of expression model.Among of TCE PM group,recipient DP5 mismatches accounted for 34.25%(25/73)were predicted as aGVHD high risk according to expression model.For the TCE non-PM group,both the recipient DP2 mismatches of 6.85%(5/73)and recipient DP5 mismatches of 10.86%(8/73)were predicted to be

关 键 词：人类白细胞抗原 T细胞表位 表达水平 单核苷酸多态性 造血干细胞移植 允许错配 不允许错配 

分 类 号：R457.7[医药卫生—治疗学]