HLA-E typing of more than 2.5 million potential hematopoietic stem cell donors: Methods and population-specific allele frequencies.

We developed a cost-efficient workflow for genotyping HLA-E by NGS and applied it for genotyping more than 2.5 million potential stem cell donors. The data obtained were used to determine HLA-E allele frequency distributions for 104 populations. Our results confirm the known dominance of the alleles E*01:01 and E*01:03, which have a combined frequency of more than 0.99 in 97 of the 104 populations. E*01:01 is more frequent in Africa and the western part of South America, E*01:03 in Southeast and East Asia. E*01:03 shows a pronounced regional substructure at the high-resolution level with E*01:03:01G being particularly common in a large connected region extending from Turkey to China, E*01:03:02G in Northwestern Europe and E*01:03:03 in Central and Eastern Europe as well as Central Asia. The presented results are relevant both as a basis for further population genetics studies and for optimizing stem cell donor searches.

A comparative reference study for the validation of HLA-matching algorithms in the search for allogeneic hematopoietic stem cell donors and cord blood units.

The accuracy of human leukocyte antigen (HLA)-matching algorithms is a prerequisite for the correct and efficient identification of optimal unrelated donors for patients requiring hematopoietic stem cell transplantation. The goal of this World Marrow Donor Association study was to validate established matching algorithms from different international donor registries by challenging them with simulated input data and subsequently comparing the output. This experiment addressed three specific aspects of HLA matching using different data sets for tasks of increasing complexity. The first two tasks targeted the traditional matching approach identifying discrepancies between patient and donor HLA genotypes by counting antigen and allele differences. Contemporary matching procedures predicting the probability for HLA identity using haplotype frequencies were addressed by the third task. In each task, the identified disparities between the results of the participating computer programs were analyzed, classified and quantified. This study led to a deep understanding of the algorithms participating and finally produced virtually identical results. The unresolved discrepancies total to less than 1%, 4% and 2% for the three tasks and are mostly because of individual decisions in the design of the programs. Based on these findings, reference results for the three input data sets were compiled that can be used to validate future matching algorithms and thus improve the quality of the global donor search process.

An update to the HLA Nomenclature Guidelines of the World Marrow Donor Association, 2012.

For more than two decades, international cooperation and information technology have been playing key roles in the identification of suitable unrelated donors and cord blood units for hematopoietic SCT. To ensure consistent coding and interpretation of HLA data among the linked computer systems, the World Marrow Donor Association has standardized the extensions of the World Health Organization (WHO) Nomenclature for factors of the HLA system applied in practice. The first version of this report published in 2007 has become the reference for the technical validation of HLA information on donors and patients in the context of search and matching and is used by registries of volunteer unrelated hematopoietic stem cell donors and umbilical cord blood banks throughout the world. The present update became necessary after the major revision of the WHO HLA nomenclature in April 2010. It now covers issues arising when alleles are withdrawn or renamed because of the continuous updating of the WHO HLA nomenclature. In addition, formal validation and interpretation rules for the so-called 'multiple allele codes' have been added.