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Determination of HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in heart failure patients.
ESC Heart Failure 2019 January 24
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.
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.
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