Overview of the study design
We performed NGS-based HLA typing to assess potentially enriched HLA alleles in patients with thoroughly documented delayed hypersensitivity to penicillins. We also performed the HLA-based typing to assess the potentially enriched HLA-DRB3alleles in 20 patients with documented immediate hypersensitivity to penicillins. We compared the delayed-hypersensitivity cases with the immediate ones to estimate the risk of nonimmediate reactions related toHLA-DRB3 among patients with hypersensitivity to penicillins. Finally, we replicated the results using GWAS data from our previous study of a large Spanish population.11 We performed per-variant and per-haplotype association studies on the haplotype and variants significantly associated with the risk of delayed hypersensitivity.