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Although HLA-DPB1 has long been considered of lesser importance in the selection of an unrelated donor (URD) hematologic stem cell transplantation, currently in many instances the DPB1 type of the donor is relevant or even critical. At present, however, only a minority of registry donors are DPB1 typed. It is also unclear to what extent the DPB1 alleles are linked to the 5-locus HLA-A-, B-, C-, DRB1, -DQB1 haplotypes. We sought to study whether there is such a linkage by using donors in the Finnish Stem Cell Registry as the study population. The 6-locus HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 haplotype frequencies were estimated from a group of 43,365 Finnish registry donors using the German National Bone Marrow Registry algorithm. Five-locus haplotype (HLA-A, -B, -C, -DRB1, -DQB1) and HLA-DPB1 allele frequencies were calculated as marginal frequencies of the estimated 6-locus haplotype frequencies. The Finnish average frequency of individual DPB1 alleles was compared with their respective frequencies in association with individual 5-locus HLA haplotypes (haplotype-specific frequencies). Finally, the probability of DPB1 matching in 10/10 matched URD transplants was assessed. Haplotype-specific DPB1 frequencies differed significantly from the average DPB1 frequencies in 81 of 100 most frequent Finnish 5-locus HLA haplotypes, including some infrequent DPB1 alleles that were associated almost exclusively with certain individual 5-locus haplotypes. Five-locus haplotypes that are enriched in Finland but rare among other Europeans carried stronger DPB1 associations than haplotypes that are frequent European-wide. Finally, 10/10 matched transplants from domestic registry donors were significantly more likely to also be DPB1 matched than those from foreign donors. The results indicate an extension of linkage disequilibrium in the MHC complex in the Finnish population. With continuing upfront DPB1 typing of registry donors, it will be possible to perform similar extended 6-locus haplotype frequency estimations also in other registries. The associations are likely to be population specific but may be weaker in more heterogeneous populations. In the future the results might be used to predict the probability of DPB1 match or permissive/nonpermissive DPB1 mismatch for non-DPB1 typed donors in registry donor searches., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Europeans have often been considered a homogenous group in registry donor match predictions, but it is now evident that HLA haplotype frequencies vary across the European continent. Earlier studies have indicated that Finns in northeastern Europe have unique HLA characteristics, and the increasing availability of high-resolution registry donor data is now making more detailed comparisons possible. In the first phase of the present study, estimated HLA haplotype frequencies in stem cell donor registries of Finland and its neighbors Sweden and Russia were calculated using the algorithm of the German National Bone Marrow Donor Registry (ZKRD) and their frequencies were compared with one another and also with that of Germany. Virtual donor searches for 1492 high-resolution typed Finnish patients in the Finnish, Swedish and German registries were then performed, using individual match predictions for each registry. In the last phase, the impact of specifically Finnish-enriched HLA haplotypes on Finnish patients and the use of Finnish registry donors was assessed by analyzing 647 consecutive hematopoietic stem cell transplantation (HSCT) donor searches and 40 exported Finnish HSCTs. The Finnish HLA landscape was more homogenous than the 3 other studied populations, but also genetically distinct from them. The match predictions found a probable 10/10 match for 71%, 41%, and 31% of the Finnish patients in the German, Finnish, and Swedish registries, respectively. Thirty-four of Finland's 100 most frequent HLA haplotypes were represented with a frequency of <.0003 in Germany, and with an 8- to 3262-fold greater frequency in Finland than in Germany. Patients carrying these Finnish-enriched haplotypes were less likely to receive a matched HSCT but more likely to receive it from a domestic donor. Registry donors carrying them were more likely to donate stem cells, both nationally and internationally. The Finnish HLA isolate has a significant impact on both Finnish patients and registry donors, explaining the high use of national registry donors for Finnish patients. Haplotype frequency estimations are an important tool for small registries as well, to help optimize donor match predictions and the size of individual registries., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)