Predicting HLA-DPB1 permissive probabilities through a DPB1 prediction service towards the optimization of HCT donor selection

Sajulga, Ray; Madbouly, Abeer; Fingerson, Stephanie; Gragert, Loren; Bashyal, Pradeep; Bolon, Yung–Tsi; Maiers, Martin

doi:10.1016/j.humimm.2021.06.010

Cited by 6 publications

(2 citation statements)

References 29 publications

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“…While DPB1 epitope status is provided when donors are high resolution typed for DPB1, there are no probabilistic estimates to guide their search when the typing is missing or ambiguous. Therefore, confirmatory typing at the DPB1 typing locus had not been informed by immunogenetics reference data until 2021 when NMDP released a prototype tool for DPB1 match predictions 19 .…”

Section: Introductionmentioning

confidence: 99%

“…In this study we present HLA match likelihoods for patients searching the US unrelated stem cell donor registry for a more optimal donor with A, B, C, DRB1 high resolution allele matching and TCE permissive mismatching at DPB1. We also sought to analyze linkage disequilibrium patterns between HLA loci to understand why DPB1 TCE categories are often highly predictable when the other HLA loci are typed 19 . We hypothesized that if tools for prioritizing donors for additional typing based on likelihood of match at DPB1 were available, better results could be achieved with reduced time and cost.…”

Section: Introductionmentioning

confidence: 99%

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Unrelated Stem Cell Donor HLA Match Likelihoods in the US Registry Incorporating HLA-DPB1 Permissive Mismatching

Gragert

Spellman

Shaw

et al. 2022

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Donor-recipient HLA matching at the DPB1 locus improves the outcomes of hematopoietic cell transplantation (HCT). Retrospective outcomes studies found that in transplants matched for all 8 alleles of the A, B, C, and DRB1 loci at high resolution (8-of-8 match), few transplants were also allele-matched at the DPB1 locus. DPB1 allele matching was thought to be logistically impractical, however a DPB1-permissive mismatch model based on T-cell epitope (TCE) reactivity expands the proportion of suitable donors. To understand the likelihood of success for finding a DPB1-permissive donor, we sought to expand population genetic match likelihood models for the US unrelated donor registry, National Marrow Donor Program (NMDP). After extending HLA haplotype frequency estimates to include the DPB1 locus, our models found that the likelihood of having a DPB1-permissive donor was not much lower than the 8-of-8 match likelihoods. A maximum of 5 additional donors would need to be typed to find a more optimal DPB1-permissive donor at least 90% of the time. Linkage disequilibrium patterns between the DPB1 locus and other classical HLA loci varied markedly by haplotype and population, indicating that the known recombination hotspot between DQ and DP gene complexes has not had uniform impact, thus DPB1-permissive donors are easier to identify within minority populations. DPB1 TCE categories were highly predictable from HLA typing at other loci when imputed with extended haplotype frequency data. Our overall results indicate that registry search strategies that seek a more optimally matched HCT donor encompassing HLA-DPB1 permissibility are likely to be highly productive.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%