Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort.
Adult
Anti-Bacterial Agents
/ adverse effects
Cephalosporins
/ adverse effects
Cohort Studies
Drug Hypersensitivity
/ genetics
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
HLA-DQ alpha-Chains
/ genetics
HLA-DRB1 Chains
/ genetics
Humans
Hypersensitivity, Immediate
/ chemically induced
Male
Middle Aged
Penicillins
/ adverse effects
Phenotype
Polymorphism, Single Nucleotide
Type I hypersensitivity
allergy
anaphylaxis
cephalosporins
penicillins
pharmacogenomics
β-lactams
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
09
06
2020
revised:
27
09
2020
accepted:
05
10
2020
pubmed:
16
10
2020
medline:
25
9
2021
entrez:
15
10
2020
Statut:
ppublish
Résumé
β-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (type I) reactions mediated by antigen-specific IgE. We sought to identify genetic predisposing factors for immediate reactions to β-lactam antibiotics. Patients with a clinical history of immediate hypersensitivity reactions to either penicillins or cephalosporins, which were immunologically confirmed, were recruited from allergy clinics. A genome-wide association study was conducted on 662 patients (the discovery cohort) with a diagnosis of immediate hypersensitivity and the main finding was replicated in a cohort of 98 Spanish cases, recruited using the same diagnostic criteria as the discovery cohort. Genome-wide association study identified rs71542416 within the Class II HLA region as the top hit (P = 2 × 10 HLA-DRB1∗10:01 predisposed to immediate hypersensitivity reactions to penicillins. Further work to identify other predisposing HLA and non-HLA loci is required.
Sections du résumé
BACKGROUND
β-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (type I) reactions mediated by antigen-specific IgE.
OBJECTIVE
We sought to identify genetic predisposing factors for immediate reactions to β-lactam antibiotics.
METHODS
Patients with a clinical history of immediate hypersensitivity reactions to either penicillins or cephalosporins, which were immunologically confirmed, were recruited from allergy clinics. A genome-wide association study was conducted on 662 patients (the discovery cohort) with a diagnosis of immediate hypersensitivity and the main finding was replicated in a cohort of 98 Spanish cases, recruited using the same diagnostic criteria as the discovery cohort.
RESULTS
Genome-wide association study identified rs71542416 within the Class II HLA region as the top hit (P = 2 × 10
CONCLUSIONS
HLA-DRB1∗10:01 predisposed to immediate hypersensitivity reactions to penicillins. Further work to identify other predisposing HLA and non-HLA loci is required.
Identifiants
pubmed: 33058932
pii: S0091-6749(20)31405-6
doi: 10.1016/j.jaci.2020.10.004
pmc: PMC8100096
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Cephalosporins
0
HLA-DQ alpha-Chains
0
HLA-DQA1 antigen
0
HLA-DRB1 Chains
0
Penicillins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1830-1837.e15Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG010863
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM115305
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI139021
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R34 AI136815
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L006758/1
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
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