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

Nicoletti, Paola, Carr, Daniel F, Barrett, Sarah, McEvoy, Laurence ORCID: 0000-0002-2169-6735, Friedmann, Peter S, Shear, Neil H, Nelson, Matthew R, Chiriac, Anca M, Blanca-López, Natalia, Cornejo, Jose A
et al (show 13 more authors) (2021) Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort. Journal of Allergy and Clinical Immunology, 147 (5). 1830-+.

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<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 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.<h4>Results</h4>Genome-wide association study identified rs71542416 within the Class II HLA region as the top hit (P = 2 × 10<sup>-14</sup>); this was in linkage disequilibrium with HLA-DRB1∗10:01 (odds ratio, 2.93; P = 5.4 × 10<sup>-7</sup>) and HLA-DQA1∗01:05 (odds ratio, 2.93, P = 5.4 × 10<sup>-7</sup>). 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<sup>-9</sup>). No association with HLA-DRB1∗10:01 was identified in 268 patients with delayed hypersensitivity reactions to β-lactams.<h4>Conclusions</h4>HLA-DRB1∗10:01 predisposed to immediate hypersensitivity reactions to penicillins. Further work to identify other predisposing HLA and non-HLA loci is required.

Item Type: Article
Uncontrolled Keywords: Type I hypersensitivity, beta-lactams, penicillins, cephalo-sporins, allergy, anaphylaxis, pharmacogenomics
Depositing User: Symplectic Admin
Date Deposited: 13 Oct 2020 15:28
Last Modified: 18 Jan 2023 23:28
DOI: 10.1016/j.jaci.2020.10.004
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