RT Journal Article
T1 Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort.
A1 Nicoletti, Paola
A1 Carr, Daniel F
A1 Barrett, Sarah
A1 McEvoy, Laurence
A1 Friedmann, Peter S
A1 Shear, Neil H
A1 Nelson, Matthew R
A1 Chiriac, Anca M
A1 Blanca-Lopez, Natalia
A1 Cornejo-Garcia, Jose A
A1 Gaeta, Francesco
A1 Nakonechna, Alla
A1 Torres, Maria J
A1 Caruso, Cristiano
A1 Valluzzi, Rocco L
A1 Floratos, Aris
A1 Shen, Yufeng
A1 Pavlos, Rebecca K
A1 Phillips, Elizabeth J
A1 Demoly, Pascal
A1 Romano, Antonino
A1 Blanca, Miguel
A1 Pirmohamed, Munir
K1 Type I hypersensitivity
K1 Allergy
K1 Anaphylaxis
K1 Cephalosporins
K1 Penicillins
K1 Pharmacogenomics
K1 β-lactams
AB 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.
PB Elsevier
YR 2020
FD 2020-10-05
LK http://hdl.handle.net/10668/16426
UL http://hdl.handle.net/10668/16426
LA en
NO Nicoletti P, Carr DF, Barrett S, McEvoy L, Friedmann PS, Shear NH, et al. Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort. J Allergy Clin Immunol. 2021 May;147(5):1830-1837.e15
NO Thank the Medical Research Council (MRC) Centre for Drug Safety Science for support (MR/L006758/1). P.N.was supported by the iSAEC. E.J.P. receives funding from the National Institutes of Health (grants 1P50GM115305-01, R21AI139021, R34AI136815, and 1 R01 HG010863-01) and the National Health and Medical Research Council of Australia.
DS RISalud
RD Apr 4, 2025