There are many studies on the polymorphism of the HLA system in healthy donor populations, such as registries of unrelated bone marrow donors. Investigations on the characterization of the HLA complex in hematopoietic stem cell transplant (HSCT) patients, however, are scarce, at least in the Spanish population. This study presents a large‐scale analysis of allelic diversity and HLA distribution at a high‐resolution level in 2886 patients undergoing HSCT in Spanish centres of the “Grupo Español de Trasplante Hematopoyético y Terapia Celular” during a period of 11 years. Allelic diversity analysis identified 67 HLA‐A, 133 HLA‐B, 60 HLA‐C, 63 HLA‐DRB1, 24 HLA‐DQB1 and 27 HLA‐DPB1 different alleles. Rare alleles were detected among which 33 alleles had not been reported in the European catalog of common and well‐documented HLA alleles. Regarding the distribution of five genes‐haplotypes, it was observed that the five most frequent extended haplotypes found in our population were between the most common in other Spanish populations, both in patients and in healthy subjects. However, some particular haplotypes were also detected. Bilocus associations HLA‐C ~ B and ‐DRB1 ~ DQB1 were analyzed in order to predict the probability of finding 10/10 matched donors in registries. We found HLA‐B alleles showing a great diversity of combinations with HLA‐C alleles and unusual associations involving a negative predicting factor. In the field of adoptive therapies, our work supports the necessity to expand further research of TCR‐engineered cells, adoptive transfer of virus‐specific T‐cells and vaccines to target HLA alleles other than A*02:01. HLA alleles such as A*01:01, A*03:01, A*24:02, B*44:03, B*07:02 or B*51:01, might be considered new targets due to its high frequency in our population.

中文翻译：

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西班牙同种异体造血干细胞移植受者：人类白细胞抗原特性和多样性的高分辨率分析

在健康供体人群中，例如无关的骨髓供体的注册表中，有许多关于HLA系统多态性的研究。然而，对于造血干细胞移植（HSCT）患者中HLA复合物的表征研究很少，至少在西班牙人群中很少。这项研究在西班牙中心的“ GrupoEspañolde TrasplanteHematopoyéticoy Terapia Celular ”西班牙中心接受HSCT的2886位患者进行了高分辨率的大规模等位基因多样性和HLA分布分析在11年的时间里。等位基因多样性分析确定了67个HLA-A，133个HLA-B，60个HLA-C，63个HLA-DRB1、24个HLA-DQB1和27个HLA-DPB1不同等位基因。在欧洲常见和有据可查的HLA等位基因目录中未检出稀有等位基因，其中33个等位基因尚未报告。关于五种基因单倍型的分布，据观察，在我们的人群中发现的五种最常见的扩展单倍型在患者和健康受试者中在其他西班牙人群中最常见。但是，也检测到一些特定的单倍型。分析Bilocus关联HLA-C〜B和‐DRB1〜DQB1，以预测在注册表中找到10/10匹配供体的可能性。我们发现HLA-B等位基因与HLA-C等位基因的组合表现出极大的多样性，并且涉及负预测因子的异常关联。在过继疗法领域，我们的工作支持以下方面的必要性：扩大对TCR工程化细胞的进一步研究，病毒特异性T细胞和疫苗的过继转移以靶向除HLA等位基因以外的其他目标A * 02：01。HLA等位基因如A * 01：01，A * 03：01，A * 24：02，B * 44：03，B * 07：02或B * 51：01可能由于其高频率而被认为是新的靶标在我们的人口中。