A novel HLA‐B variant, <i>HLA‐B*14:02:16</i>, discovered by amplicon‐based next‐generation sequencing

Balz, Vera; Fischer, Johannes C.; Krause, Stefan W.; Enczmann, Juergen

doi:10.1111/tan.13384

Cited by 4 publications

(3 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intriguingly, “in silico” analyses assign high cumulative calculated HLA-allele affinity scores to the three protective HLA alleles identified by the current study, adding to the biological plausibility of the association observed. The identification of protective alleles belonging to both HLA class I and class II is in line with the general immune-mechanistic concept that both CD4 helper cells (interacting via HLA class II with antigen presenting cells) and CD8 cytotoxic cells (interacting via HLA class I) play important roles in SARS-CoV-2 antiviral immune responses [ 18 ]. Of note, we did not find any similar association of COVID-19 duration (or severity) with class I HLA alleles (C2, Bw4) binding to distinct killer-cell immunoglobulin-like receptors thought to play key roles in the first-line innate antiviral immune response.…”

Section: Discussionmentioning

confidence: 85%

“…An amplicon-based next generation sequencing (NGS) approach was used as described before [ 18 , 19 ]. Briefly, amplification of exons 2, 3, and 4 of HLA class I and HLA-DPB1 genes, and exons 2 and 3 of HLA-DRB1 and HLA-DQB1 (in parallel with selected exons of the blood group system genes AB0 and Rh as well as exon 3 of the CCR5 gene for detection of CCR5 wt or CCR5 del32 or other mutations causing a truncated CC chemokine receptor type 5) were carried out in six multiplex polymerase chain reactions (PCRs).…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background COVID-19, the pandemic disease caused by infection with SARS-CoV-2, may take highly variable clinical courses, ranging from symptom-free and pauci-symptomatic to fatal disease. The goal of the current study was to assess the association of COVID-19 clinical courses controlled by patients’ adaptive immune responses without progression to severe disease with patients’ Human Leukocyte Antigen (HLA) genetics, AB0 blood group antigens, and the presence or absence of near-loss-of-function delta 32 deletion mutant of the C–C chemokine receptor type 5 (CCR5). Patient and methods An exploratory observational study including 157 adult COVID-19 convalescent patients was performed with a median follow-up of 250 days. The impact of different HLA genotypes, AB0 blood group antigens, and the CCR5 mutant CD195 were investigated for their role in the clinical course of COVID-19. In addition, this study addressed levels of severity and morbidity of COVID-19. The association of the immunogenetic background parameters were further related to patients’ humoral antiviral immune response patterns by longitudinal observation. Results Univariate HLA analyses identified putatively protective HLA alleles (HLA class II DRB1*01:01 and HLA class I B*35:01, with a trend for DRB1*03:01). They were associated with reduced durations of disease instead decreased (rather than increased) total anti-S IgG levels. They had a higher virus neutralizing capacity compared to non-carriers. Conversely, analyses also identified HLA alleles (HLA class II DQB1*03:02 und HLA class I B*15:01) not associated with such benefit in the patient cohort of this study. Hierarchical testing by Cox regression analyses confirmed the significance of the protective effect of the HLA alleles identified (when assessed in composite) in terms of disease duration, whereas AB0 blood group antigen heterozygosity was found to be significantly associated with disease severity (rather than duration) in our cohort. A suggestive association of a heterozygous CCR5 delta 32 mutation status with prolonged disease duration was implied by univariate analyses but could not be confirmed by hierarchical multivariate testing. Conclusion The current study shows that the presence of HLA class II DRB1*01:01 and HLA class I B*35:01 is of even stronger association with reduced disease duration in mild and moderate COVID-19 than age or any other potential risk factor assessed. Prospective studies in larger patient populations also including novel SARS-CoV-2 variants will be required to assess the impact of HLA genetics on the capacity of mounting protective vaccination responses in the future.

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Patients Materials and Methodsmentioning

confidence: 99%

Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Further, differences in vaccine types, SARS-CoV-2 variants, genotyping methods, and algorithms for predicting HLA haplotype may also impact results [95,96]. For instance, a range of sequencing or genotyping technologies were used, including Ion GeneStudio [97], PacBio [98], Illumina, and Affymetrix [99][100][101]. The targeted next-generation sequencing panels and/or differences in the PCR techniques applied had different levels of resolution for HLA calling.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

HLA Variation and SARS-CoV-2 Specific Antibody Response

Wolday

Fung

Morgan

et al. 2023

Viruses

View full text Add to dashboard Cite

Differences in SARS-CoV-2-specific immune responses have been observed between individuals following natural infection or vaccination. In addition to already known factors, such as age, sex, COVID-19 severity, comorbidity, vaccination status, hybrid immunity, and duration of infection, inter-individual variations in SARS-CoV-2 immune responses may, in part, be explained by structural differences brought about by genetic variation in the human leukocyte antigen (HLA) molecules responsible for the presentation of SARS-CoV-2 antigens to T effector cells. While dendritic cells present peptides with HLA class I molecules to CD8+ T cells to induce cytotoxic T lymphocyte responses (CTLs), they present peptides with HLA class II molecules to T follicular helper cells to induce B cell differentiation followed by memory B cell and plasma cell maturation. Plasma cells then produce SARS-CoV-2-specific antibodies. Here, we review published data linking HLA genetic variation or polymorphisms with differences in SARS-CoV-2-specific antibody responses. While there is evidence that heterogeneity in antibody response might be related to HLA variation, there are conflicting findings due in part to differences in study designs. We provide insight into why more research is needed in this area. Elucidating the genetic basis of variability in the SARS-CoV-2 immune response will help to optimize diagnostic tools and lead to the development of new vaccines and therapeutics against SARS-CoV-2 and other infectious diseases.

show abstract

Nomenclature for factors of the HLA system, update October, November, and December 2018

Marsh

2019

Int J Immunogenetics

View full text Add to dashboard Cite

A novel HLA‐B variant, HLA‐B14:02:16*, discovered by amplicon‐based next‐generation sequencing

Abstract: HLA-B14:02:16 differs from B14:02:01:01 by a synonymous nucleotide substitution in codon 141.

Cited by 4 publications

References 3 publications

Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19

Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19

HLA Variation and SARS-CoV-2 Specific Antibody Response

Nomenclature for factors of the HLA system, update October, November, and December 2018

Contact Info

Product

Resources

About

A novel HLA‐B variant, HLA‐B*14:02:16, discovered by amplicon‐based next‐generation sequencing

Abstract: HLA-B*14:02:16 differs from B*14:02:01:01 by a synonymous nucleotide substitution in codon 141.

Cited by 4 publications

References 3 publications

Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19

Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19

HLA Variation and SARS-CoV-2 Specific Antibody Response

Nomenclature for factors of the HLA system, update October, November, and December 2018

Contact Info

Product

Resources

About

A novel HLA‐B variant, HLA‐B14:02:16*, discovered by amplicon‐based next‐generation sequencing

Abstract: HLA-B14:02:16 differs from B14:02:01:01 by a synonymous nucleotide substitution in codon 141.