HLA-DQA103:02-DQB103:03 is the Dominant Immunogenic Heterodimer for Posttransplant HLA-DQ De Novo DSA Development in a Cohort of Chinese Kidney Transplant Patients.

IF 5 2区医学 Q1 IMMUNOLOGY

Transplantation Pub Date : 2025-08-26 DOI:10.1097/TP.0000000000005445

Zhaoru Huang, Yonghua Feng, Xiangjun Liu, Xiaobo Li, Jinfeng Li, Lei Liu, Hongchang Xie, Zhigang Wang, Junxiang Wang, Yongchuang Yan, Frans H J Claas, Guiwen Feng, Wenjun Shang

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引用次数: 0

Abstract

Background: Eplets, acting as specificity determinants on donor HLA antigen molecules, may induce the formation of de novo donor-specific antibodies (dnDSAs) by the recipient's B cells posttransplantation. HLA-DQ DSAs are the most common type of DSAs that target mismatched donor HLA-DQ antigens. The HLA-DQ protein exists as a heterodimer, consisting of HLA-DQA1 and HLA-DQB1 molecules. The specific risk of each mismatched HLA-DQ dimer contributing to dnDSA formation remains underexplored.

Methods: A total of 434 kidney transplant donor/recipient pairs from Zheng Zhou University First Affiliated Hospital, who underwent the transplant procedure between September 2016 and November 2020, were included in this analysis. All were DSA-negative pretransplant. For each HLA-DQ heterodimer, the total incidence of dnDSA, alpha chain-specific dnDSA, and beta chain-specific dnDSA after kidney transplant was analyzed. The dnDSA formation rates of different mismatched HLA-DQ dimers were compared and their haplotype association with specific HLA-DRB1 protein were determined.

Results: In this study, 38 HLA-DQ dnDSAs were detected, with 28 to HLA-DQB1 and 10 to HLA-DQA1. HLA-DQA1*03:02-DQB1*03:03 dimer had the highest dnDSA formation rate of 28.3%. The HLA-DQA1*05:xx-DQB1*03:01 and HLA-DQA1*05:xx-DQB1*02:xx, which are known for their high immunogenicity in previous studies, showed a relatively low DSA formation rate of 4.3%. The common DQB1*01:xx-DQB1*05:xx and DQA1*01:xx-DQB1*06:xx dimers had DSA formation rates of 1.8% and 3.9%, respectively. The high immunogenic HLA-DQA1*03:02-DQB1*03:03 dimer formed haplotype with DRB1*09:01 (98%), whereas the low immunogenic HLA-DQA1*02:01-DQB1*03:03 dimer formed exclusively haplotype with DRB1*07:01.

Conclusions: The DQA1*03:02-DQB1*03:03 dimer and the HLA-DRB1*09:01-HLA-DQA1*03:02-DQB1*03:03 haplotype turned out to be the most immunogenic in inducing HLA-DQ dnDSA in this Northern Han Chinese cohort.

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HLA-DQA1*03:02-DQB1*03:03是中国肾移植患者移植后HLA-DQ De Novo DSA发展的显性免疫原性异二聚体。

背景：Eplets作为供者HLA抗原分子的特异性决定因素，可能诱导受体B细胞在移植后形成新的供者特异性抗体（ddnsa）。HLA-DQ dsa是针对不匹配供体HLA-DQ抗原的最常见的dsa类型。HLA-DQ蛋白以异源二聚体形式存在，由HLA-DQA1和HLA-DQB1分子组成。每种不匹配的HLA-DQ二聚体对dnDSA形成的具体风险仍未得到充分研究。方法：将2016年9月至2020年11月期间在郑州大学第一附属医院接受肾移植手术的434对肾移植供体/受体纳入分析。移植前均为dsa阴性。分析各HLA-DQ异源二聚体肾移植后dnDSA、α链特异性dnDSA和β链特异性dnDSA的总发生率。比较不同错配HLA-DQ二聚体的dnDSA形成率，并测定其与特异性HLA-DRB1蛋白的单倍型关联。结果：本研究共检测到38个HLA-DQ ddsa，其中28个为HLA-DQB1, 10个为HLA-DQA1。HLA-DQA1*03:02-DQB1*03:03二聚体的dnDSA形成率最高，为28.3%。HLA-DQA1*05:xx- dqb1 *03:01和HLA-DQA1*05:xx- dqb1 *02:xx在既往研究中具有较高的免疫原性，其DSA形成率相对较低，为4.3%。常见二聚体DQB1*01:xx-DQB1*05:xx和DQA1*01:xx-DQB1*06:xx的DSA形成率分别为1.8%和3.9%。高免疫原性HLA-DQA1*03:02-DQB1*03:03二聚体与DRB1*09:01（98%）形成单倍型，低免疫原性HLA-DQA1*02:01-DQB1*03:03二聚体与DRB1*07:01形成单倍型。结论：DQA1*03:02-DQB1*03:03二聚体和HLA-DRB1*09:01-HLA-DQA1*03:02-DQB1*03:03单倍型在该北方汉族人群中诱导HLA-DQ dnDSA的免疫原性最强。

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来源期刊

Transplantation 医学-免疫学

CiteScore

8.50

自引率

11.30%

发文量

1906

审稿时长

1 months

期刊介绍： The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year. Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal. Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed. The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.