%0 Journal Article
%A Nicoletti, Paola
%A Carr, Daniel F
%A Barrett, Sarah
%A McEvoy, Laurence
%A Friedmann, Peter S
%A Shear, Neil H
%A Nelson, Matthew R
%A Chiriac, Anca M
%A Blanca-Lopez, Natalia
%A Cornejo-Garcia, Jose A
%A Gaeta, Francesco
%A Nakonechna, Alla
%A Torres, Maria J
%A Caruso, Cristiano
%A Valluzzi, Rocco L
%A Floratos, Aris
%A Shen, Yufeng
%A Pavlos, Rebecca K
%A Phillips, Elizabeth J
%A Demoly, Pascal
%A Romano, Antonino
%A Blanca, Miguel
%A Pirmohamed, Munir
%T Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort.
%D 2020
%U http://hdl.handle.net/10668/16426
%X 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 × 10-14); 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. HLA-DRB1∗10:01 predisposed to immediate hypersensitivity reactions to penicillins. Further work to identify other predisposing HLA and non-HLA loci is required.
%K Type I hypersensitivity
%K Allergy
%K Anaphylaxis
%K Cephalosporins
%K Penicillins
%K Pharmacogenomics
%K β-lactams
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