HLA最新文献

HLA genes exhibit a high degree of polymorphism, contributing to genetic variability known to influence immune responses to infection. Here we investigate associations between HLA polymorphism and serological and T-lymphocyte responses to the BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines within a population receiving maintenance haemodialysis (HD) for End-Stage Renal Disease (ESRD). Our primary objective was to identify HLA alleles associated with diminished serological and T-cellular responsiveness to vaccination. As a secondary objective, the associations between HLA type and COVID-19 disease outcomes were investigated using an independent ESRD cohort (n = 327). This aimed to determine if the alleles associated with poor vaccine response were also linked to unfavourable infection outcomes. In the main study, serum from 225 SARS-CoV-2 infection-naïve patients was HLA-typed using high-resolution Next Generation Sequencing, and serological titres were analysed for the presence of SARS-CoV-2 spike glycoprotein-specific antibodies after two doses of vaccination. A subset of patients (n = 33) was also tested for a T-lymphocyte response. Overall, 89% (n = 200) of patients seroconverted, but only 18% (n = 6) of the cellular response subgroup had a positive T-lymphocyte response. The HLA class II alleles DPB1*104:01, DRB1*04:03 and DRB1*14:04 and HLA class I alleles B*08:01 and B*18:01 were found to significantly correlate with seronegativity, and DQB1*06:01 correlated with serological responsiveness. We were unable to analyse the effect of HLA on disease outcome and T-lymphocyte response due to sample size limitations. Our results suggest pathways for further research and begin to elucidate the relationship between HLA polymorphism and immune responses in the vulnerable ESRD population.

The bovine leukocyte antigen (BoLA) comprises four regions that contain a high density of polymorphic genes and frequently show gene copy number variations (CNV). Therefore, genotyping BoLA using genome-wide resequencing is difficult. This study aimed to develop four probe sets for resequencing of the BoLA region using a hybridization capture target next–generation sequencing (NGS) method. This proof of concept showed and discussed the several applications of the used strategy. DNAs from nine Japanese Black cows and one Holstein cow were genotyped for BoLA-DRB3 using PCR sequence-based typing (SBT). DNA libraries were constructed using the KAPA HyperPlus Kit, and BoLA DNA sequences were enriched using the SeqCap EZ kit and four custom-made probes. Based on preliminary results, the probe set BoLA2 was selected for further analysis. This analysis resulted in a mean coverage of 90.8% with an average depth of 108 reads. A total of 113,646 SNPs and 17,995 indels were detected, several of which have previously been described in the dbSNP database. This allowed the genotyping of class II genes, including BoLA-DRB3. A comparison between target resequencing and PCR-SBT assays did not show conflicts between the BoLA-DRB3 genotyping results. CNV analysis based on read number inferred that the BoLA-DQA1, BoLA-DQA2, BoLA-DQA5, and BoLA-DQB genes would be present in the homozygous or heterozygous states or absent, allowing for the definition of four class II and three class I haplotypes. In addition, CNV of non-classical class I genes were also observed. In conclusion, results show that approach used in this study is a cost–effective strategy for sequencing large samples for many research purposes.

HLA-DQA1*05:05:24 differs from HLA-DQA1*05:05:01 by one synonymous nucleotide in codon 27 in Exon 2.

The novel HLA-C*07:1145N allele was first described in a potential bone marrow donor from Brazil.

Identification of the novel HLA-B*58:01:51 allele in a Brazilian bone marrow donor.

HLA-A*03:01:130 differs from HLA-A*03:01:01:01 by one nucleotide substitution in codon 266 in exon 4.

HLA-DPB1*04:02:27 differs from HLA-DPB1*04:02:01:01 by one nucleotide substitution in codon 193 in exon 4.

The novel HLA-C*01:283 allele differs from C*01:02:01:01 by change of C → T in exon 4.