HLA-DPB1 TCE错配及表达模型在同胞相合造血干细胞移植中的评估  

Assessment study of HLA-DPB1 TCE mismatching and expression model in 10/10 HLA-matched sibling-hematopoietic cell transplantations

作　　者：齐珺[1] 王天菊[1] 郝剑 尚利侠 王满妮[1] 武君华[1] 陈乐 王小芳[1] 房婕[1] 李恒新 QI Jun;WANG Tianju;HAO Jian;SHANG Lixia;WANG Manni;WU Junhua;CHEN Le;WANG Xiaofang;FANG Jie;LI Hengxin(High-resolution HLA Typing Laboratory of the Chinese Marrow Donor Program,Shaanxi Blood Center,Institute of Xi′an Blood Bank,Xi'an 710061,China)

机构地区：[1]陕西省血液中心西安市中心血站中华骨髓库HLA高分辨分型确认实验室,陕西西安710061

出　　处：《中国输血杂志》2020年第9期876-880,共5页Chinese Journal of Blood Transfusion

基　　金：中国输血协会威高科研基金(CSBT-WG-2017-06);西安市卫生健康委员会科研项目Ⅰ类(J201701003)。

摘　　要：目的回顾性调查陕西籍汉族同胞相合造血干细胞移植(HSCT)供受者HLA-DPB1配合情况以及HLA-DPB1 3′-UTR rs9277534分型,运用TCE(T-cell epitope)和表达模型进行风险评估。方法应用聚合酶链反应-测序分型(PCR-SBT)、下一代测序(NGS-ION S5TM)技术、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)等方法对64对HLA-A,B,C,DRB1,DQB1 10/10相合的同胞供受者进行HLA-DPB1基因分型和新等位基因的确证,对DPB1错配供受者rs9277534 SNP位点进行测序,依据DPB1 T-Cell Epitope Algorithm version 3.0和rs9277534基因型进行TCE模型和表达模型预测。结果在64例HSCT受者中共计检出14种DPB1等位基因,其中DPB1*05∶01∶01G、DPB1*02∶01和DPB1*04∶01∶01G频率分布最高,分别占31.25%、20.31%和16.41%;发现新等位基因1例,于2020年6月26日被正式命名为HLA-DPB1*1120∶01;检出的3对错配供受者均为单一DPB1位点不合,DPB1座位热点交换率为4.69%,且均为不允许错配(non-PM);rs9277534基因型分别为AG/AG、AG/GG和AA/AG,供受对1较供受对2和3可能存在更高发生急性移植物抗宿主病(aGVHD)的风险。结论同胞相合HSCT中仍需关注HLA-DPB1呈现的TCE不允许错配及表达模型所预示的移植后风险。Objective To retrospectively investigate HLA-DPB1 mismatching and the DPB1 3′-UTR rs9277534 typing in 10/10 HLA-matched sibling-hematopoietic cell transplantation(HSCT) of the Han ethnic in Shaanxi, and use TCE(T-cell epitope) and expression models for risk assessment.Methods The HLA-DPB1 genes and identification of a novel allele from 64 pairs of HLA-A,B,C,DRB1,DQB1 10/10 matched sibling recipients and donors were retrospectively genotyped using polymerase chain reaction-sequence-based typing(PCR-SBT), next-generation sequencing(NGS) with Ion Torrent S5 platform and sequence specific oligonueleotide probes(SSO) with LABScan■ 3 D platform.The rs9277534 SNP of DPB1-mismatched donors and recipients were sequenced, and TCE and expression models were assessed according to DPB1 T-Cell Epitope Algorithm version 3.0 and rs9277534 genotype. Results A total of 14 DPB1 alleles were detected in 64 HSCT recipients, among which DPB1~*05∶01∶01G, DPB1~*02∶01 and DPB1~*04∶01∶01G had the three highest frequency with 31.25%, 20.31% and 16.41%, respectively. The official name HLA-DPB1~*1120∶01 assigned by WHO HLA Nomenclature Committee on June 26, 2020. The detected three pairs of mismatches with a single DPB1 allele were all non-permissive mismatches(non-PM). The recombination hotspot occurred with a rate of 4.69%. The rs9277534 genotypes were AG/AG, AG/GG and AA/AG in recipient-donor(RD) 1—3, respectively. RD1 might have a higher risk of developing acute graft-versus-host disease(aGVHD) than RD2 and RD3.Conclusion It still needs to pay attention to the post-transplant risks predicted by HLA-DPB1 TCE and expression models in HLA-matched sibling HSCT.

关 键 词：造血干细胞移植 HLA-DPB1 T细胞表位 rs9277534 急性移植物抗宿主病 

分 类 号：R457.1[医药卫生—治疗学] S723.3[医药卫生—临床医学]