HLA binding-groove motifs are associated with myocarditis induction after Pfizer-BioNTech BNT162b2 vaccination.
Pfizer-BioNTech BNT162b2 vaccination
human leukocyte antigens
myocarditis
Journal
European journal of clinical investigation
ISSN: 1365-2362
Titre abrégé: Eur J Clin Invest
Pays: England
ID NLM: 0245331
Informations de publication
Date de publication:
09 Dec 2023
09 Dec 2023
Historique:
revised:
16
11
2023
received:
31
08
2023
accepted:
25
11
2023
medline:
10
12
2023
pubmed:
10
12
2023
entrez:
10
12
2023
Statut:
aheadofprint
Résumé
We found a higher incidence of myocarditis in young males who had received at least two Pfizer-BioNTech BNT162b2 vaccinations. The human leukocyte antigens (HLA) are known to play an important role in infectious and autoinflammatory diseases. We hypothesized that certain HLA alleles might be associated with vaccination-induced myocarditis. HLA typing was performed using next-generation sequencing technology with the Illumina Iseq100 platform. HLA class I and II loci were genotyped in 29 patients with post-vaccination myocarditis and compared with HLA data from 300 healthy controls. We demonstrate that the DRB1*14:01, DRB1*15:03 alleles and the motifs in HLA-A - Leu62 and Gln63, which are part of binding pocket B and HLA-DR Tyr47, His60, Arg70 and Glu74, which are part of binding pockets P4, P7 and P9, were significantly associated with disease susceptibility. Our findings suggest that immunogenetic fingerprints in HLA peptide-binding grooves may affect the presentation of peptides derived from the Pfizer-BioNTech BNT162b2 vaccination to T cells and induce an inflammatory process that results in myocarditis.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
We found a higher incidence of myocarditis in young males who had received at least two Pfizer-BioNTech BNT162b2 vaccinations. The human leukocyte antigens (HLA) are known to play an important role in infectious and autoinflammatory diseases. We hypothesized that certain HLA alleles might be associated with vaccination-induced myocarditis.
METHODS
METHODS
HLA typing was performed using next-generation sequencing technology with the Illumina Iseq100 platform. HLA class I and II loci were genotyped in 29 patients with post-vaccination myocarditis and compared with HLA data from 300 healthy controls.
RESULTS
RESULTS
We demonstrate that the DRB1*14:01, DRB1*15:03 alleles and the motifs in HLA-A - Leu62 and Gln63, which are part of binding pocket B and HLA-DR Tyr47, His60, Arg70 and Glu74, which are part of binding pockets P4, P7 and P9, were significantly associated with disease susceptibility.
CONCLUSIONS
CONCLUSIONS
Our findings suggest that immunogenetic fingerprints in HLA peptide-binding grooves may affect the presentation of peptides derived from the Pfizer-BioNTech BNT162b2 vaccination to T cells and induce an inflammatory process that results in myocarditis.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14142Subventions
Organisme : Israel Science Foundation
ID : 3048/22
Organisme : Jewish Community Federation and Endowment Fund
ID : 20220747/21293816
Informations de copyright
© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.
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