Extended HLA Haplotypes and Their Impact on DPB1 Matching of Unrelated Hematologic Stem Cell Transplant Donors

Linjama, Tiina; Räther, Caroline; Ritari, Jarmo; Peräsaari, Juha; Eberhard, Hans-Peter; Korhonen, Matti; Koskela, Satu

doi:10.1016/j.bbmt.2019.07.008

Cited by 11 publications

(12 citation statements)

References 44 publications

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“…However, when taking into account of matching for HLA-DPB1 loci, the likelihood of finding an available 10/10(DBP1) HLA matched donor is 20% while 55% for finding 9/10(DBP1) HLA matched donor. Similar finding was observed in a Finnish retrospective study in which only 32.6% of local donors or 19.3% of both local and foreign donors were HLA-DPB1 matched with HSCT patients (36). In our data, the matching probability increases to 38% when taking into account of the DPB1 T-cellepitope (TCE) permissive mismatching model.…”

Section: Resultssupporting

confidence: 90%

Revisit of Optimal Donor Number Estimation in the Hong Kong Bone Marrow Donor Registry

Cheung

Lui

et al. 2021

Front. Immunol.

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High resolution typing of the HLA-DPB1 locus for patient who requested for hematopoietic stem cell transplantation (HSCT) workup has recently become mandatory by the National Marrow Donor Program (NMDP) in order to facilitate matching between donors and recipients for better outcomes. The likelihood of identifying HLA matched donors in Hong Kong, on top of the existing HLA-A, -B, -C, and -DRB1 loci, is revisited in this study. HLA-A, -B, -C, -DRB1 and -DPB1 genotypes of 5,266 volunteer unrelated Chinese donors from the Hong Kong Bone Marrow Donor Registry (HKBMDR), were included in this study. Matching models were employed to determine the matching probabilities for 10/10(DPB1) and 9/10(DPB1) HLA match. The matching probabilities are 20% at 10/10(DPB1) HLA match and 55% at 9/10(DPB1) match, based on the existing 130,000 donors in the HKBMDR. The likelihoods of match become 27% and 65% respectively, by increasing the registry to 250,000. However, if DPB T-cell-epitope (TCE) model is considered in the matching, the probability will increase to 46% at 10/10 DPB1 permissive mismatching. Our findings provide vital information about the future planning on the targeted recruitment size, HLA typing and search strategies of the donor registry and arose the transplant physicians’ acceptability to 9/10(DBP1) or 10/10(DBP1) HLA match. Nevertheless, the marrow donor registry has planned for increasing the registry size and bringing down the age of recruited donors which will ultimately enhance patient outcome.

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Section: Resultssupporting

confidence: 90%

Revisit of Optimal Donor Number Estimation in the Hong Kong Bone Marrow Donor Registry

Cheung

Lui

et al. 2021

Front. Immunol.

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“…Extending the matching criteria to HLA-DPB1 may be challenging due to the recombination hot spot between HLA-DQB1 and HLA-DPB1 [10]. In the present study, HLA-A to HLA-DPB1 haplotypes and haplotype frequencies (Table 2) were equivalent to the HLA-A-DPB1 haplotypes identi ed earlier in the Finnish population [31].…”

Section: Discussionsupporting

confidence: 63%

“…The expected frequency refers to the calculated frequency (haplotype frequency p 2 ) of each homozygote based on haplotype frequencies of Linjama et al [31]. * = homozygosity of all the samples representing the haplotype con rmed by clinical grade HLA typing.…”

Section: Hla-bmentioning

confidence: 99%

Blood donor biobank and HLA imputation as a resource of HLA homozygous cells for therapeutic and research use

Clancy

Hyvärinen

Ritari

et al. 2022

Preprint

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BackgroundAllogeneic therapeutic cells may be rejected if they express HLA alleles not found in the recipient. As finding cell donors with a full HLA match to a recipient requires vast donor pools, use of HLA homozygous cells has been suggested as an alternative. HLA homozygous cells should be well tolerated by those who carry at least one copy of donor HLA alleles. HLA-A-B homozygotes could be valuable for HLA-matched thrombocyte products. We evaluated the feasibility of blood donor biobank and HLA imputation for identification of potential cell donors homozygous for HLA alleles.MethodsWe imputed HLA-A, - B, -C, -DRB1, -DQA1, -DQB1, and -DPB1 alleles from genotypes of 20,737 Finnish blood donors in the Blood Service Biobank. We confirmed homozygosity by sequencing HLA alleles in 30 samples and by examining 36,161 MHC-located polymorphic DNA markers. Results317 individuals (1.5%), representing 41 different haplotypes, were found to be homozygous for HLA-A, -B, -C, -DRB1, -DQA1 and -DQB1 alleles. Ten most frequent haplotypes homozygous for HLA-A to -DQB1 were HLA-compatible to 49.5% and three most frequent homozygotes to 30.4% of the Finnish population. Ten most frequent HLA-A-B homozygotes were compatible to 75.3% and three most frequent haplotypes to 42.6% of the Finnish population. HLA homozygotes had a low level of heterozygosity in MHC-located DNA markers, in particular in HLA haplotypes enriched in Finland.ConclusionsThe present study shows that HLA imputation in a blood donor biobank of reasonable size can be used to identify HLA homozygous blood donors suitable for cell therapy, HLA-typed thrombocytes and research. The homozygotes were HLA-compatible to a large fraction of the Finnish population. Regular blood donors reported to have positive attitude to research donation appear a good option for these purposes. Differences in population frequencies of HLA haplotypes emphasize the need for population specific collections of HLA homozygous samples.

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“…N Number of individuals homozygous for the haplotype. The expected frequency refers to the calculated frequency (haplotype frequency p 2 ) of each homozygote based on haplotype frequencies of Linjama et al [ 37 ]. Heterozygous markers % refers to the average percentage of heterozygous markers found in the MHC region by haplotype.…”

Section: Methodsmentioning

confidence: 99%

Blood donor biobank and HLA imputation as a resource for HLA homozygous cells for therapeutic and research use

et al. 2022

Self Cite

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Background Allogeneic therapeutic cells may be rejected if they express HLA alleles not found in the recipient. As finding cell donors with a full HLA match to a recipient requires vast donor pools, the use of HLA homozygous cells has been suggested as an alternative. HLA homozygous cells should be well tolerated by those who carry at least one copy of donor HLA alleles. HLA-A-B homozygotes could be valuable for HLA-matched thrombocyte products. We evaluated the feasibility of blood donor biobank and HLA imputation for the identification of potential cell donors homozygous for HLA alleles. Methods We imputed HLA-A, -B, -C, -DRB1, -DQA1, -DQB1 and -DPB1 alleles from genotypes of 20,737 Finnish blood donors in the Blood Service Biobank. We confirmed homozygosity by sequencing HLA alleles in 30 samples and by examining 36,161 MHC-located polymorphic DNA markers. Results Three hundred and seventeen individuals (1.5%), representing 41 different haplotypes, were found to be homozygous for HLA-A, -B, -C, -DRB1, -DQA1 and -DQB1 alleles. Ten most frequent haplotypes homozygous for HLA-A to -DQB1 were HLA-compatible with 49.5%, and three most frequent homozygotes to 30.4% of the Finnish population. Ten most frequent HLA-A-B homozygotes were compatible with 75.3%, and three most frequent haplotypes to 42.6% of the Finnish population. HLA homozygotes had a low level of heterozygosity in MHC-located DNA markers, in particular in HLA haplotypes enriched in Finland. Conclusions The present study shows that HLA imputation in a blood donor biobank of reasonable size can be used to identify HLA homozygous blood donors suitable for cell therapy, HLA-typed thrombocytes and research. The homozygotes were HLA-compatible with a large fraction of the Finnish population. Regular blood donors reported to have positive attitude to research donation appear a good option for these purposes. Differences in population frequencies of HLA haplotypes emphasize the need for population-specific collections of HLA homozygous samples.

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Extended HLA Haplotypes and Their Impact on DPB1 Matching of Unrelated Hematologic Stem Cell Transplant Donors

Cited by 11 publications

References 44 publications

Revisit of Optimal Donor Number Estimation in the Hong Kong Bone Marrow Donor Registry

Revisit of Optimal Donor Number Estimation in the Hong Kong Bone Marrow Donor Registry

Blood donor biobank and HLA imputation as a resource of HLA homozygous cells for therapeutic and research use

Blood donor biobank and HLA imputation as a resource for HLA homozygous cells for therapeutic and research use

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