{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:59:09Z","timestamp":1783702749891,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T00:00:00Z","timestamp":1636848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nonimmediate (delayed)\u2010allergic reactions to penicillins are common and some of them can be life\u2010threatening. 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using next\u2010generation 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 <jats:italic>in silico<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u201323.32; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.0001). The haplotype (ACAA) from rs9268835, rs6923504, rs6903608, and rs9268838\u00a0genetic variants of the HLA\u2010DRB3\u00a0genomic region was significantly associated with an increased risk of delayed hypersensitivity to penicillins (OR, 1.7; 95% CI: 1.06\u20131.92; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.001), but not immediate hypersensitivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We showed that the <jats:italic>HLA<\/jats:italic>\u2010<jats:italic>DRB3<\/jats:italic>\u00a0locus is strongly associated with an increased risk of delayed penicillin hypersensitivity, at least in Southwestern Europe. The determination of <jats:italic>HLA<\/jats:italic>\u2010<jats:italic>DRB3*02<\/jats:italic>:<jats:italic>02<\/jats:italic> alleles in the risk management of severe delayed hypersensitivity to penicillins should be evaluated further in larger population samples of different origins.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15147","type":"journal-article","created":{"date-parts":[[2021,10,23]],"date-time":"2021-10-23T09:30:38Z","timestamp":1634981438000},"page":"1827-1834","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Next\u2010generation sequencing and genotype association studies reveal the association of <i>HLA\u2010DRB3*02:02<\/i> with delayed hypersensitivity to penicillins"],"prefix":"10.1111","volume":"77","author":[{"given":"Antonino","family":"Romano","sequence":"first","affiliation":[{"name":"INSERM UMR_S 1256 Nutrition, Genetics, and Environmental Risk Exposure (NGERE) Faculty of Medicine of Nancy University of Lorraine  Nancy France"},{"name":"Oasi Research Institute\u2010IRCCS  Troina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9731-4529","authenticated-orcid":false,"given":"Abderrahim","family":"Oussalah","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1256 Nutrition, Genetics, and Environmental Risk Exposure (NGERE) Faculty of Medicine of Nancy University of Lorraine  Nancy France"},{"name":"Department of Molecular Medicine Division of Biochemistry, Molecular Biology, and Nutrition University Hospital of Nancy  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Chery","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1256 Nutrition, Genetics, and Environmental Risk Exposure (NGERE) Faculty of Medicine of Nancy University of Lorraine  Nancy France"},{"name":"Department of Molecular Medicine Division of Biochemistry, Molecular Biology, and Nutrition University Hospital of Nancy  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa\u2010Maria","family":"Gu\u00e9ant\u2010Rodriguez","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1256 Nutrition, Genetics, and Environmental Risk Exposure (NGERE) Faculty of Medicine of Nancy University of Lorraine  Nancy France"},{"name":"Department of Molecular Medicine Division of Biochemistry, Molecular Biology, and Nutrition University Hospital of Nancy  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Gaeta","sequence":"additional","affiliation":[{"name":"Allergy Unit Columbus Hospital Fondazione Policlinico A. Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-8735","authenticated-orcid":false,"given":"Jose\u2010Antonio","family":"Cornejo\u2010Garcia","sequence":"additional","affiliation":[{"name":"Allergy Unit Hospital Regional Universitario de M\u00e1laga\u2010UMA\u2010ARADyAL  Malaga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Rouyer","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1256 Nutrition, Genetics, and Environmental Risk Exposure (NGERE) Faculty of Medicine of Nancy University of Lorraine  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Josse","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Division of Biochemistry, Molecular Biology, and Nutrition University Hospital of Nancy  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8852-8077","authenticated-orcid":false,"given":"Cristobalina","family":"Mayorga","sequence":"additional","affiliation":[{"name":"Allergy Unit Hospital Regional Universitario de M\u00e1laga\u2010UMA\u2010ARADyAL  Malaga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-471X","authenticated-orcid":false,"given":"Maria\u2010Jose","family":"Torres","sequence":"additional","affiliation":[{"name":"Allergy Unit Hospital Regional Universitario de M\u00e1laga\u2010UMA\u2010ARADyAL  Malaga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5067-042X","authenticated-orcid":false,"given":"Jean\u2010Louis","family":"Gu\u00e9ant","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1256 Nutrition, Genetics, and Environmental Risk Exposure (NGERE) Faculty of Medicine of Nancy 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