Dataset Information

Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort.

ABSTRACT:

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^-14); this was in linkage disequilibrium with HLA-DRB1∗10:01 (odds ratio, 2.93; P = 5.4 × 10^-7) and HLA-DQA1∗01:05 (odds ratio, 2.93, P = 5.4 × 10^-7). Haplotype analysis identified that HLA-DRB1∗10:01 was a risk factor even without the HLA-DQA1∗01:05 allele. The association with HLA-DRB1∗10:01 was replicated in another cohort, with the meta-analysis of the discovery and replication cohorts showing that HLA-DRB1∗10:01 increased the risk of immediate hypersensitivity at a genome-wide level (odds ratio, 2.96; P = 4.1 × 10^-9). No association with HLA-DRB1∗10:01 was identified in 268 patients with delayed hypersensitivity reactions to β-lactams.

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.

SUBMITTER: Nicoletti P

PROVIDER: S-EPMC8100096 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort.

Nicoletti Paola P Carr Daniel F DF Barrett Sarah S McEvoy Laurence L Friedmann Peter S PS Shear Neil H NH Nelson Matthew R MR Chiriac Anca M AM Blanca-López Natalia N Cornejo-García José A JA Gaeta Francesco F Nakonechna Alla A Torres Maria J MJ Caruso Cristiano C Valluzzi Rocco L RL Floratos Aris A Shen Yufeng Y Pavlos Rebecca K RK Phillips Elizabeth J EJ Demoly Pascal P Romano Antonino A Blanca Miguel M Pirmohamed Munir M

The Journal of allergy and clinical immunology 20201013 5

<h4>Background</h4>β-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (type I) reactions mediated by antigen-specific IgE.<h4>Objective</h4>We sought to identify genetic predisposing factors for immediate reactions to β-lactam antibiotics.<h4>Methods</h4>Patients with a clinical history of immediate hypersensitivity reactions to either penicillins or cephalosporins, which were immunologically confirmed, were recruited from all ...[more]

PMID: 33058932

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Dataset Information

Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort.

Background

Objective

Methods

Results

Conclusions

Publications

Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort.

Similar Datasets

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