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抗体验证的表位错配负荷估计,在一个大型欧洲供者队列中 2 字段 HLA 分辨率与推断比较。

Estimation of Antibody-Verified Eplet Mismatch Load, 2-Field HLA Resolution vs Imputation in a Large Cohort of European Donors.

机构信息

Immunology Department, Marqués de Valdecilla University Hospital, Santander, Spain; Autoimmunity and Transplantation Research Group, Research Institute "Marqués de Valdecilla" (IDIVAL), Santander, Spain.

Josep Carreras Foundation, Barcelona, Spain.

出版信息

Transplant Proc. 2022 Nov;54(9):2414-2418. doi: 10.1016/j.transproceed.2022.09.011. Epub 2022 Nov 1.

DOI:10.1016/j.transproceed.2022.09.011
PMID:36333253
Abstract

BACKGROUND

The assessment of class II eplet mismatch load is useful to determine the risk of chronic rejection in solid organ transplantation. However, high-resolution (2-field) HLA typing is mandatory to accurately define eplet mismatches. The imputation of the most frequent allele has been used in retrospective studies. Here, we sought to investigate the concordant of antibody-verified (AbV) eplet load in different class II alelles between real 2-field HLA typing and HLA imputed by most frequent allele in a large White cohort.

MATERIALS AND METHODS

The allelic frequency of the different HLA class II loci was calculated using a database of high-resolution typing of 23,628 voluntary Spanish bone marrow donors obtained from the Spanish Registry of Bone Marrow Donors, managed by the Josep Carreras Foundation. The AbV eplet count in the different class II alleles was performed using the HLA-Matchmaker v3.1 algorithm.

RESULTS

The probability of imputing the correct allele compared to the most frequent for DRB1 and DQB1 loci was 69.3% and 53.0%, respectively. However, studying the less frequent alleles, the same AbV eplet load was observed in 82.22% and 76.15%, respectively.

CONCLUSIONS

Our data show that despite the potential error in the imputation of class II HLA typing, the number of AbV eplets is not significantly over- or underestimated in our population. Until high-resolution typing is widely established for solid organ transplantation, retrospective studies of AbV eplet mismatch load with imputed high-resolution types provide an acceptable outcome in White people.

摘要

背景

评估 II 类 eplet 错配负荷对于确定实体器官移植中慢性排斥的风险很有用。然而,要准确定义 eplet 错配,必须进行高分辨率(2 字段)HLA 分型。在回顾性研究中,已使用最常见等位基因的推断。在这里,我们试图研究在一个大型白人队列中,真实 2 字段 HLA 分型和 HLA 最常见等位基因推断之间不同 II 类等位基因中抗体验证(AbV)eplet 负荷的一致性。

材料和方法

使用从西班牙骨髓捐赠者登记处管理的由 Josep Carreras 基金会管理的 23628 名自愿西班牙骨髓捐赠者的高分辨率 2 字段 HLA 分型数据库计算不同 HLA II 类基因座的等位基因频率。使用 HLA-Matchmaker v3.1 算法在不同的 II 类等位基因中进行 AbV eplet 计数。

结果

与最常见的 DRB1 和 DQB1 基因座相比,正确推断等位基因的概率分别为 69.3%和 53.0%。然而,研究较少的等位基因时,相同的 AbV eplet 负荷分别在 82.22%和 76.15%中观察到。

结论

我们的数据表明,尽管 II 类 HLA 分型推断存在潜在误差,但在我们的人群中,AbV eplet 的数量不会被显著高估或低估。在高分辨率分型广泛应用于实体器官移植之前,使用推断的高分辨率类型进行 AbV eplet 错配负荷的回顾性研究在白人中提供了可接受的结果。

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