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We characterized 549 new human leukocyte antigen (HLA) class I and class II alleles found in newly registered stem cell donors as a result of high-throughput HLA typing. New alleles include 101 HLA-A, 132 HLA-B, 105 HLA-C, 2 HLA-DRB1, 89 HLA-DQB1 and 120 HLA-DPB1 alleles. Mainly, new alleles comprised single nucleotide variations when compared with homologous sequences. We identified nonsynonymous nucleotide mutations in 70.7% of all new alleles, synonymous variations in 26.4% and nonsense substitutions in 2.9% (null alleles). Some new alleles (55, 10.0%) were found multiple times, HLA-DPB1 alleles being the most frequent among these. Furthermore, as several new alleles were identified in individuals from ethnic minority groups, the relevance of recruiting donors belonging to such groups and the importance of ethnicity data collection in donor centers and registries is highlighted. [ABSTRACT FROM AUTHOR]

How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design., (© 2024. The Author(s).)

Background: Although there are many possible causes for cervical dystonia (CD), a specific etiology cannot be identified in most cases. Prior studies have suggested a relationship between autoimmune disease and some cases of CD, pointing to possible immunological mechanisms., Objective: The goal was to explore the potential role of multiple different immunological mechanisms in CD., Methods: First, a broad screening test compared neuronal antibodies in controls and CD. Second, unbiased blood plasma proteomics provided a broad screen for potential biologic differences between controls and CD. Third, a multiplex immunoassay compared 37 markers associated with immunological processes in controls and CD. Fourth, relative immune cell frequencies were investigated in blood samples of controls and CD. Finally, sequencing studies investigated the association of HLA DQB1 and DRB1 alleles in controls versus CD., Results: Screens for anti-neuronal antibodies did not reveal any obvious abnormalities. Plasma proteomics pointed towards certain abnormalities of immune mechanisms, and the multiplex assay pointed more specifically towards abnormalities in T lymphocytes. Abnormal immune cell frequencies were identified for some CD cases, and these cases clustered together as a potential subgroup. Studies of HLA alleles indicated a possible association between CD and DRB1*15:03, which is reported to mediate the penetrance of autoimmune disorders., Conclusions: Altogether, the association of CD with multiple different blood-based immune measures point to abnormalities in cell-mediated immunity that may play a pathogenic role for a subgroup of individuals with CD., Competing Interests: Declaration of competing interest NO COI., (Copyright © 2024. Published by Elsevier Ltd.)

The HLA-B*53:69 allele differs from HLA-B*53:01:01:01 by two nucleotide changes in exon 3., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Between January 2018 and June 2021, the Ezer Mizion recruited 223,960 donors. All donors were typed for their HLA class I and II alleles at high resolution by Next Generation Sequencing techniques. Comparison between the sequences obtained from these donors and those in the IPD-IMGT/HLA Database, revealed 122 Novel HLA alleles that were found in 133 donors. Most of the alleles, 94 (77%) were identified in the HLA class I genes (30, 35, and 29 in HLA-A, -B, and -C, respectively), and 28 (23%) were detected in the HLA class II genes (9 in HLA-DRB1 and -DQB1 and 10 in -DPB1). Most of these novel alleles, 106 (86.9%) comprised single nucleotide variation (SNV), 9 (7.4%) present multiple amino acids variation, 4 and 3 were generated because of deletions and insertions, respectively. Ten of these novel alleles were seen to be null alleles., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A nucleotide mutation in codon 75 of HLA-C*04:01:01:01 results in a novel allele HLA-C*04:279N., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The identity of histocompatibility loci, besides human leukocyte antigen (HLA), remains elusive. The major histocompatibility complex (MHC) class I MICA gene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45-3.11; P < 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94-7.39; P < 0.001; HR, 9.92; 95% CI: 7.43-13.20; P < 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31-199.41; P = 0.002; HR, 82.67; 95% CI: 33.67-202.97; P < 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05-1.58; P = 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02-2.86; P = 0.041). In conclusion, assessment of MICA matching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted., (© 2022. The Author(s).)

One nucleotide substitution in Codon 58 of HLA-C*06:02:01:01 results in a novel allele, HLA-C*06:195., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One nucleotide substitution in codon 112 of HLA-B*15:349:01 results in a novel allele, HLA-B*15:349:02., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One nucleotide substitution in codon 73 of HLA-A*01:01:01:01 results in a novel allele, HLA-A*01:211., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-A*68:227 differs from HLA-A*68:84 by two single nucleotide substitutions in codon 10 and 90., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-DPB1*10:01:05 differs from HLA-DPB1*10:01:01:01 by a single synonymous nucleotide substitution in exon 2, 38 G>A., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One nucleotide substitution in codon 89 of HLA-B*38:02:01:01 results in a novel allele, HLA-B*38:64., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One nucleotide substitution in codon 85 of HLA-DPB1*04:01:01:01 results in a novel allele, HLA-DPB1*454:01., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Nucleotide substitutions in codon 38 of HLA-DQB1*05:03:01:01 result in a novel allele, HLA-DQB1*05:66:01., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One nucleotide substitution in codon 38 of HLA-DQB1*06:01:01:01 results in a novel allele, HLA-DQB1*06:132., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One nucleotide substitution in codon 87 of HLA-DQB1*05:02:01:01 results in a novel allele, HLA-DQB1*05:116., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One nucleotide substitution in codon 84 of HLA-DPB1*02:01:02:01 results in a novel allele, HLA-DPB1*526:01., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

DNA substitutions from codons 69 to 71 of HLA-B*35:05:01:01 result in a novel allele, HLA-B*35:368., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Novel allele HLA-DPB1*906:01 is possibly a recombinant between DPB1*04:02:01:01 and DPB1*06:01:01:01., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well-documented (≥5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole., (© 2020 The Authors. HLA published by John Wiley & Sons Ltd.)

Between 2008 and April 2018, we recruited more than 37 000 potential Arab donors to the Hadassah Bone Marrow Donor Registry, all of whom were typed for high resolution HLA-A, -B, and -DRB1. In addition, more than 22% of them were also typed for their HLA-C and -DQB1 alleles. A comparison of the sequences obtained from these donors with the IPD-IMGT/HLA Database showed 33 novel alleles from five loci (HLA-A, -B, -C, -DR, -DQ). All of these novel HLA alleles were detected in the local Arab communities; 79% of these alleles have not been described in other groups yet and remain unique to the local Arab communities., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Summary: HLA*LA implements a new graph alignment model for human leukocyte antigen (HLA) type inference, based on the projection of linear alignments onto a variation graph. It enables accurate HLA type inference from whole-genome (99% accuracy) and whole-exome (93% accuracy) Illumina data; from long-read Oxford Nanopore and Pacific Biosciences data (98% accuracy for whole-genome and targeted data) and from genome assemblies. Computational requirements for a typical sample vary between 0.7 and 14 CPU hours per sample., Availability and Implementation: HLA*LA is implemented in C++ and Perl and freely available as a bioconda package or from https://github.com/DiltheyLab/HLA-LA (GPL v3)., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2019. Published by Oxford University Press.)

One nucleotide substitution in codon 46 of HLA-DQB1*05:01:01:01 results in a new allele, HLA-DQB1*05:115., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-DPB1*417:01:02 differs from HLA-DPB1*417:01:01 by a synonymous nucleotide substitution at codon 43., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One nucleotide replacement in codon 50 of HLA-C*07:02:01:01 results in a novel allele, HLA-C*07:465., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Nucleotide substitutions at residues 105 and 106 of HLA-B*58:01:01:01 result in a novel allele, HLA-B*58:74., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)