Allele‐level HLA compatibility in cord blood transplantation has been associated with better transplant outcomes and is recommended as a selection criterion. It is also a crucial aspect for other therapeutic applications involving cord blood‐derived cells. Determination of high‐resolution HLA frequencies is an important step towards improving the quality of cord blood banks. We analyzed HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 allele frequencies in 5458 high‐quality cord blood units from the Barcelona Cord Blood Bank and identified 275 class I and 121 class II HLA alleles. A*02:01, B*44:03, C*07:01, DRB1*07:01 and DQB1*03:01 were the most frequent alleles at each locus. We detected 26 novel alleles and were able to determine the presence or absence of some null alleles, including C*04:09N, in a large number of units. We also analyzed maternal HLA typing information for 1877 units to determine real haplotype frequencies and linkage disequilibrium. A*29:02‐B*44:03‐C*16:01‐DRB1*07:01‐DQB1*02:02 was the most frequent HLA haplotype and the DRB1‐DQB1 gene pair contained the two‐locus haplotypes with the strongest linkage disequilibrium values. Four of the 11 unique haplotypes identified in the HLA‐homozygous cord blood units were the top‐ranking haplotypes identified and were present in 18% of the cohort. This is the first study to report on HLA allele and haplotype frequencies for umbilical cord blood units from the Barcelona Cord Blood Bank and the largest study to date involving two fields of HLA resolution typing of Spanish registry data.
Aims
Cell therapy can be used to repair functionally impaired organs and tissues in humans. Although autologous cells have an immunological advantage, it is difficult to obtain high cell numbers for therapy. Well‐characterized banks of cells with human leukocyte antigens (HLA) that are representative of a given population are thus needed. The present study investigates the HLA allele and haplotype frequencies in a cohort of heart failure (HF) patients.
Methods and results
We carried out the HLA typing and the allele and haplotype frequency analysis in 247 ambulatory HF patients. We determined HLA class I (A, B, and C) and class II (DRB1 and DQB1) using next‐generation sequencing technology. The allele frequencies were obtained using Python for Population Genomics (PyPop) software, and HLA haplotypes were estimated using HaploStats. A total of 30 HLA‐A, 56 HLA‐B, 23 HLA‐C, 36 HLA‐DRB1, and 15 HLA‐DQB1 distinct alleles were identified within the studied cohort. The genotype frequencies of all five HLA loci were in Hardy–Weinberg equilibrium. We detected differences in HLA allele frequencies among patients when the etiological cause of HF was considered. There were a total of 494 five‐loci haplotypes, five of which were present six or more times. Moreover, the most common estimated HLA haplotype was HLA‐A*01:01, HLA‐B*08:01, HLA‐C*07:01, HLA‐DRB1*03:01, and HLA‐DQB1*02:01 (6.07% haplotype frequency per patient). Remarkably, the 11 most frequent haplotypes would cover 31.17% of the patients of the cohort in need of allogeneic cell therapy.
Conclusions
Our findings could be useful for improving allogeneic cell administration outcomes without concomitant immunosuppression.
We report here the identification of a novel DQB1*06 allele, DQB1*0618, found in a bone marrow donor. The new allele was detected during routine DNA-based HLA typing by an ambiguous pattern of probe hybridization, obtained by polymerase chain reaction using sequence-specific oligonucleotides (PCR-SSO). Molecular cloning and sequencing confirmed that the new allele is identical to DQB1*0609 at exon 2 except for 3 nucleotide substitutions at positions 353, 356 and 367, also found in other alleles. These nucleotide changes may explain its anomalous reactivity.
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