Next‐generation sequencing and genotype association studies reveal the association of HLA‐DRB302:02 with delayed hypersensitivity to penicillins

Background Nonimmediate (delayed)‐allergic reactions to penicillins are common and some of them can be life‐threatening. The genetic factors influencing these reactions are unknown/poorly known/poorly understood. We assessed the genetic predictors of a delayed penicillin allergy that cover the HLA l...

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Published in:Allergy (Copenhagen) 2022-06, Vol.77 (6), p.1827-1834
Main Authors: Romano, Antonino, Oussalah, Abderrahim, Chery, Celine, Guéant‐Rodriguez, Rosa‐Maria, Gaeta, Francesco, Cornejo‐Garcia, Jose‐Antonio, Rouyer, Pierre, Josse, Thomas, Mayorga, Cristobalina, Torres, Maria‐Jose, Guéant, Jean‐Louis
Format: Article
Language:English
Subjects:
Alleles
amoxicillin
Antibiotics
beta‐lactams
drug allergy
Drug Hypersensitivity - epidemiology
Gene frequency
Genetic diversity
Genetic factors
genome‐wide association
Genotype
Genotypes
Genotyping
Haplotypes
High-Throughput Nucleotide Sequencing
Histocompatibility antigen HLA
HLA-DRB3 Chains - genetics
HLA‐DRB3
Humans
Hypersensitivity (delayed)
Hypersensitivity (immediate)
Hypersensitivity, Delayed - chemically induced
Hypersensitivity, Delayed - genetics
Hypersensitivity, Immediate - complications
Major histocompatibility complex
nonimmediate reactions
Penicillin
penicillins
Penicillins - adverse effects
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Summary:Background Nonimmediate (delayed)‐allergic reactions to penicillins are common and some of them can be life‐threatening. The genetic factors influencing these reactions are unknown/poorly known/poorly understood. We assessed the genetic predictors of a delayed penicillin allergy that cover the HLA loci. Methods Using next‐generation sequencing (NGS), we genotyped the MHC region in 24 patients with delayed hypersensitivity compared with 20 patients with documented immediate hypersensitivity to penicillins recruited in Italy. Subsequently, we analyzed in silico Illumina Immunochip genotyping data that covered the HLA loci in 98 Spanish patients with delayed hypersensitivity and 315 with immediate hypersensitivity compared to 1,308 controls. Results The two alleles DRB3*02:02:01:02 and DRB3*02:02:01:01 were reported in twenty cases with delayed reactions (83%) and ten cases with immediate reactions (50%), but not in the Allele Frequency Net Database. Bearing at least one of the two alleles increased the risk of delayed reactions compared to immediate reactions, with an OR of 8.88 (95% CI, 3.37–23.32; p 
ISSN:0105-4538
1398-9995
DOI:10.1111/all.15147