ABSTRACT
Assessing donor/recipient HLA compatibility at the eplet level requires second field DNA typings but these are not always available. These can be estimated from lower-resolution data either manually or with computational tools currently relying, at best, on data containing typing ambiguities. We gathered NGS typing data from 61,393 individuals in 17 French laboratories, for loci A, B, and C (100% of typings), DRB1 and DQB1 (95.5%), DQA1 (39.6%), DRB3/4/5, DPB1, and DPA1 (10.5%). We developed HaploSFHI, a modified iterative maximum likelihood algorithm, to impute second field HLA typings from low- or intermediate-resolution ones. Compared with the reference tools HaploStats, HLA-EMMA, and HLA-Upgrade, HaploSFHI provided more accurate predictions across all loci on two French test sets and four European-independent test sets. Only HaploSFHI could impute DQA1, and solely HaploSFHI and HaploStats provided DRB3/4/5 imputations. The improved performance of HaploSFHI was due to our local and nonambiguous data. We provided explanations for the most common imputation errors and pinpointed the variability of a low number of low-resolution haplotypes. We thus provided guidance to select individuals for whom sequencing would optimize incompatibility assessment and cost-effectiveness of HLA typing, considering not only well-imputed second field typing(s) but also well-imputed eplets.
Subject(s)
High-Throughput Nucleotide Sequencing , Tissue Donors , Humans , Alleles , Haplotypes , Histocompatibility Testing , HLA Antigens/genetics , Gene FrequencyABSTRACT
The selection of a donor is an essential element in allogeneic hematopoietic stem cell transplantation. In the absence of an HLA-matched related donor, the selection of an unrelated donor is considered, and is currently the most common type of allogenic donor used in practice. Many criteria are considered for the selection when multiple donors are available, particularly in case of partial match. The aim of this workshop is to assist in the selection of an unrelated donor, in keeping with recent data from the literature.
Subject(s)
Bone Marrow Transplantation , Hematopoietic Stem Cell Transplantation , Humans , Unrelated Donors , Donor Selection , Societies, MedicalABSTRACT
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients show lower humoral vaccine responsiveness than immunocompetent individuals. HLA diversity, measured by the HLA evolutionary divergence (HED) metrics, reflects the diversity of the antigenic repertoire presented to T cells, and has been shown to predict response to cancer immunotherapy. We retrospectively investigated the association of HED with humoral response to SARS-CoV-2 vaccine in allo-HSCT recipients. HED was calculated as pairwise genetic distance between alleles at HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci in recipients and their donors. Low anti-spike IgG levels (<30 BAU/mL) were associated with short time from allo-SCT and low donor DPB1-HED, mostly related to donor DPB1 homozygosity. The diversity of donor HLA-DP molecules, assessed by heterozygosity or sequence divergence, may thus impact the efficacy of donor-derived CD4 T cells to sustain vaccine-mediated antibody response in allo-HSCT recipients.
ABSTRACT
HLA-DQA1*01:81 differs from HLA-DQA1*01:02:01:01 by one nucleotide substitution in codon 153 in exon 3.
