{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:24:03Z","timestamp":1780590243577,"version":"3.54.1"},"reference-count":100,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2015,6,26]],"date-time":"2015-06-26T00:00:00Z","timestamp":1435276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI103348"],"award-info":[{"award-number":["R01 AI103348"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5R01AI103348-02"],"award-info":[{"award-number":["5R01AI103348-02"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jacionline.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Allergy and Clinical Immunology"],"published-print":{"date-parts":[[2015,8]]},"DOI":"10.1016\/j.jaci.2015.06.022","type":"journal-article","created":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T13:10:54Z","timestamp":1438866654000},"page":"236-244","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":85,"title":["New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity"],"prefix":"10.1016","volume":"136","author":[{"given":"Munir","family":"Pirmohamed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Ostrov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Kevin","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jaci.2015.06.022_bib1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1136\/bmj.329.7456.15","article-title":"Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients","volume":"329","author":"Pirmohamed","year":"2004","journal-title":"BMJ"},{"key":"10.1016\/j.jaci.2015.06.022_bib2","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1021\/tx980058f","article-title":"Role of drug disposition in drug hypersensitivity: a chemical, molecular, and clinical perspective","volume":"11","author":"Park","year":"1998","journal-title":"Chem Res Toxicol"},{"key":"10.1016\/j.jaci.2015.06.022_bib3","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1124\/pr.113.007450","article-title":"Idiosyncratic adverse drug reactions: current concepts","volume":"65","author":"Uetrecht","year":"2013","journal-title":"Pharmacol Rev"},{"key":"10.1016\/j.jaci.2015.06.022_bib4","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1146\/annurev-med-050913-022745","article-title":"T cell-mediated hypersensitivity reactions to drugs","volume":"66","author":"Pavlos","year":"2015","journal-title":"Annu Rev Med"},{"key":"10.1016\/j.jaci.2015.06.022_bib5","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1146\/annurev-genom-090413-025419","article-title":"Personalized pharmacogenomics: predicting efficacy and adverse drug reactions","volume":"15","author":"Pirmohamed","year":"2014","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"10.1016\/j.jaci.2015.06.022_bib6","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1002\/acr.21671","article-title":"Increased frequency of DRB1*11:01 in anti-hydroxymethylglutaryl-coenzyme A\u00a0reductase-associated autoimmune myopathy","volume":"64","author":"Mammen","year":"2012","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"10.1016\/j.jaci.2015.06.022_bib7","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.1038\/ncomms5757","article-title":"Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles","volume":"5","author":"Goldstein","year":"2014","journal-title":"Nat Commun"},{"key":"10.1016\/j.jaci.2015.06.022_bib8","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/clpt.2012.189","article-title":"HLA genotype and carbamazepine-induced cutaneous adverse drug reactions: a systematic review","volume":"92","author":"Yip","year":"2012","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.jaci.2015.06.022_bib9","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/sj.tpj.6500356","article-title":"A marker for Stevens-Johnson syndrome\u2026: ethnicity matters","volume":"6","author":"Lonjou","year":"2006","journal-title":"Pharmacogenomics J"},{"key":"10.1016\/j.jaci.2015.06.022_bib10","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1056\/NEJMoa0706135","article-title":"HLA-B*5701 screening for hypersensitivity to abacavir","volume":"358","author":"Mallal","year":"2008","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jaci.2015.06.022_bib11","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/ng.379","article-title":"HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin","volume":"41","author":"Daly","year":"2009","journal-title":"Nat Genet"},{"key":"10.1016\/j.jaci.2015.06.022_bib12","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/ng.632","article-title":"A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury","volume":"42","author":"Singer","year":"2010","journal-title":"Nat Genet"},{"key":"10.1016\/j.jaci.2015.06.022_bib13","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1053\/j.gastro.2011.04.001","article-title":"Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles","volume":"141","author":"Lucena","year":"2011","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jaci.2015.06.022_bib14","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/gene.2013.2","article-title":"A PheWAS approach in studying HLA-DRB1*1501","volume":"14","author":"Hebbring","year":"2013","journal-title":"Genes Immun"},{"key":"10.1016\/j.jaci.2015.06.022_bib15","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2165\/00023210-199707020-00005","article-title":"Mechanism of clozapine-induced agranulocytosis: current status of research and implications for drug development","volume":"7","author":"Pirmohamed","year":"1997","journal-title":"CNS Drugs"},{"key":"10.1016\/j.jaci.2015.06.022_bib16","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/S0149-2918(02)80057-1","article-title":"The abacavir hypersensitivity reaction: a review","volume":"24","author":"Clay","year":"2002","journal-title":"Clin Ther"},{"key":"10.1016\/j.jaci.2015.06.022_bib17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.jaci.2014.07.047","article-title":"HLA-DRA variants predict penicillin allergy in genome-wide fine-mapping genotyping","volume":"135","author":"Gueant","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib18","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1136\/bmj.1.6127.1583","article-title":"High incidence of a concentration-dependent skin reaction in children treated with phenytoin","volume":"1","author":"Wilson","year":"1978","journal-title":"BMJ"},{"key":"10.1016\/j.jaci.2015.06.022_bib19","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/j.1365-2125.1992.tb04079.x","article-title":"Sodium valproate acutely inhibits lamotrigine metabolism","volume":"33","author":"Yuen","year":"1992","journal-title":"Br J Clin Pharmacol"},{"key":"10.1016\/j.jaci.2015.06.022_bib20","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1345\/aph.18422","article-title":"Factors influencing the incidence of lamotrigine-related skin rash","volume":"33","author":"Wong","year":"1999","journal-title":"Ann Pharmacother"},{"key":"10.1016\/j.jaci.2015.06.022_bib21","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1159\/000335613","article-title":"Genetics and the potential for predictive tests in adverse drug reactions","volume":"97","author":"Pirmohamed","year":"2012","journal-title":"Chem Immunol Allergy"},{"key":"10.1016\/j.jaci.2015.06.022_bib22","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1001\/jama.2014.7859","article-title":"Genetic variants associated with phenytoin-related severe cutaneous adverse reactions","volume":"312","author":"Chung","year":"2014","journal-title":"JAMA"},{"key":"10.1016\/j.jaci.2015.06.022_bib23","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1046\/j.1468-1293.2003.00166.x","article-title":"Epidemiological risk factors for hypersensitivity reactions to abacavir","volume":"4","author":"Easterbrook","year":"2003","journal-title":"HIV Med"},{"key":"10.1016\/j.jaci.2015.06.022_bib24","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1097\/00002030-200211080-00017","article-title":"Utility of patch testing in patients with hypersensitivity syndromes associated with abacavir","volume":"16","author":"Phillips","year":"2002","journal-title":"AIDS"},{"key":"10.1016\/j.jaci.2015.06.022_bib25","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0140-6736(02)07873-X","article-title":"Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir","volume":"359","author":"Mallal","year":"2002","journal-title":"Lancet"},{"key":"10.1016\/j.jaci.2015.06.022_bib26","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0140-6736(02)08158-8","article-title":"Genetic variations in HLA-B region and hypersensitivity reactions to abacavir","volume":"359","author":"Hetherington","year":"2002","journal-title":"Lancet"},{"key":"10.1016\/j.jaci.2015.06.022_bib27","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1097\/00008571-200406000-00002","article-title":"Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity","volume":"14","author":"Hughes","year":"2004","journal-title":"Pharmacogenetics"},{"key":"10.1016\/j.jaci.2015.06.022_bib28","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.2165\/11535540-000000000-00000","article-title":"Economic efficiency of genetic screening to inform the use of abacavir sulfate in the treatment of HIV","volume":"28","author":"Kauf","year":"2010","journal-title":"Pharmacoeconomics"},{"key":"10.1016\/j.jaci.2015.06.022_bib29","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.eimc.2009.09.010","article-title":"Cost-effectiveness analysis of HLA-B*5701 typing in the prevention of hypersensitivity to abacavir in HIV+ patients in Spain","volume":"28","author":"Nieves Calatrava","year":"2010","journal-title":"Enferm Infecc Microbiol Clin"},{"key":"10.1016\/j.jaci.2015.06.022_bib30","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1097\/QAD.0b013e3283103ce6","article-title":"The cost-effectiveness of HLA-B*5701 genetic screening to guide initial antiretroviral therapy for HIV","volume":"22","author":"Schackman","year":"2008","journal-title":"AIDS"},{"key":"10.1016\/j.jaci.2015.06.022_bib31","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1086\/504874","article-title":"Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study","volume":"43","author":"Rauch","year":"2006","journal-title":"Clin Infect Dis"},{"key":"10.1016\/j.jaci.2015.06.022_bib32","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1097\/QAD.0b013e328273bc07","article-title":"Prospective HLA-B*5701 screening and abacavir hypersensitivity: a single centre experience","volume":"21","author":"Waters","year":"2007","journal-title":"AIDS"},{"key":"10.1016\/j.jaci.2015.06.022_bib33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/QAI.0b013e318046ea31","article-title":"Prospective screening for human leukocyte antigen-B*5701 avoids abacavir hypersensitivity reaction in the ethnically mixed French HIV population","volume":"45","author":"Zucman","year":"2007","journal-title":"J Acquir Immune Defic Syndr"},{"key":"10.1016\/j.jaci.2015.06.022_bib34","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jaci.2015.05.050","article-title":"Evolving models of the immunopathogenesis of T-cell mediated drug allergy: the role of host, pathogens, and drug response","volume":"136","author":"White","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib35","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/428486a","article-title":"Medical genetics: a marker for Stevens-Johnson syndrome","volume":"428","author":"Chung","year":"2004","journal-title":"Nature"},{"key":"10.1016\/j.jaci.2015.06.022_bib36","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1097\/01.fpc.0000199500.46842.4a","article-title":"Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions","volume":"16","author":"Hung","year":"2006","journal-title":"Pharmacogenet Genomics"},{"key":"10.1016\/j.jaci.2015.06.022_bib37","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1111\/j.1528-1167.2007.01022.x","article-title":"Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese","volume":"48","author":"Man","year":"2007","journal-title":"Epilepsia"},{"key":"10.1016\/j.jaci.2015.06.022_bib38","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1111\/j.1528-1167.2008.01719.x","article-title":"Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population","volume":"49","author":"Locharernkul","year":"2008","journal-title":"Epilepsia"},{"key":"10.1016\/j.jaci.2015.06.022_bib39","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1111\/j.1528-1167.2010.02533.x","article-title":"Association between HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population","volume":"51","author":"Tassaneeyakul","year":"2010","journal-title":"Epilepsia"},{"key":"10.1016\/j.jaci.2015.06.022_bib40","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1111\/j.1365-4632.2010.04481.x","article-title":"Cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia","volume":"49","author":"Ding","year":"2010","journal-title":"Int J Dermatol"},{"key":"10.1016\/j.jaci.2015.06.022_bib41","doi-asserted-by":"crossref","first-page":"579","DOI":"10.4103\/0378-6323.57718","article-title":"Association of HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome among Indians","volume":"75","author":"Mehta","year":"2009","journal-title":"Indian J Dermatol Venereol Leprol"},{"key":"10.1016\/j.jaci.2015.06.022_bib42","doi-asserted-by":"crossref","first-page":"813","DOI":"10.2217\/14622416.7.6.813","article-title":"HLA-B locus in Caucasian patients with carbamazepine hypersensitivity","volume":"7","author":"Alfirevic","year":"2006","journal-title":"Pharmacogenomics"},{"key":"10.1016\/j.jaci.2015.06.022_bib43","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/FPC.0b013e3282f3ef9c","article-title":"A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs","volume":"18","author":"Lonjou","year":"2008","journal-title":"Pharmacogenet Genomics"},{"key":"10.1016\/j.jaci.2015.06.022_bib44","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1528-1167.2009.02269.x","article-title":"HLA class I markers in Japanese patients with carbamazepine-induced cutaneous adverse reactions","volume":"51","author":"Ikeda","year":"2010","journal-title":"Epilepsia"},{"key":"10.1016\/j.jaci.2015.06.022_bib45","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.2217\/14622416.9.11.1617","article-title":"HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis","volume":"9","author":"Kaniwa","year":"2008","journal-title":"Pharmacogenomics"},{"key":"10.1016\/j.jaci.2015.06.022_bib46","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1056\/NEJMoa1009717","article-title":"Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan","volume":"364","author":"Chen","year":"2011","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jaci.2015.06.022_bib47","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1212\/WNL.0000000000001034","article-title":"Effects of a HLA-B*15:02 screening policy on antiepileptic drug use and severe skin reactions","volume":"83","author":"Chen","year":"2014","journal-title":"Neurology"},{"key":"10.1016\/j.jaci.2015.06.022_bib48","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/tpj.2013.40","article-title":"HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis","volume":"14","author":"Genin","year":"2014","journal-title":"Pharmacogenomics J"},{"key":"10.1016\/j.jaci.2015.06.022_bib49","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1056\/NEJMoa1013297","article-title":"HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans","volume":"364","author":"McCormack","year":"2011","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jaci.2015.06.022_bib50","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1093\/hmg\/ddq537","article-title":"Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population","volume":"20","author":"Ozeki","year":"2011","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.jaci.2015.06.022_bib51","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/epi.12937","article-title":"Cost-effectiveness of screening for HLA-A*31:01 prior to initiation of carbamazepine in epilepsy","volume":"56","author":"Plumpton","year":"2015","journal-title":"Epilepsia"},{"key":"10.1016\/j.jaci.2015.06.022_bib52","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1021\/tx400460w","article-title":"HLA restriction of carbamazepine-specific T-Cell clones from an HLA-A*31:01-positive hypersensitive patient","volume":"27","author":"Lichtenfels","year":"2014","journal-title":"Chem Res Toxicol"},{"key":"10.1016\/j.jaci.2015.06.022_bib53","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1084\/jem.61.5.643","article-title":"Studies on the sensitization of animals with simple chemical compounds","volume":"61","author":"Landsteiner","year":"1935","journal-title":"J Exp Med"},{"key":"10.1016\/j.jaci.2015.06.022_bib54","doi-asserted-by":"crossref","first-page":"e41340","DOI":"10.1371\/journal.pone.0041340","article-title":"Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation","volume":"7","author":"Esser","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.jaci.2015.06.022_bib55","first-page":"709","article-title":"Quantitative relationships between sensitizing dose of DNCB and reactivity in normal subjects","volume":"53","author":"Friedmann","year":"1983","journal-title":"Clin Exp Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib56","doi-asserted-by":"crossref","first-page":"7576","DOI":"10.4049\/jimmunol.0901064","article-title":"The cutaneous biochemical redox barrier: a component of the innate immune defenses against sensitization by highly reactive environmental xenobiotics","volume":"183","author":"Pickard","year":"2009","journal-title":"J Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib57","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/sj.jid.5700581","article-title":"Investigation of mechanisms underlying the T-cell response to the hapten 2,4-dinitrochlorobenzene","volume":"127","author":"Pickard","year":"2007","journal-title":"J Invest Dermatol"},{"key":"10.1016\/j.jaci.2015.06.022_bib58","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1002\/prca.200800222","article-title":"Characterisation of flucloxacillin and 5-hydroxymethyl flucloxacillin haptenated HSA in\u00a0vitro and in\u00a0vivo","volume":"3","author":"Jenkins","year":"2009","journal-title":"Proteomics Clin Appl"},{"key":"10.1016\/j.jaci.2015.06.022_bib59","doi-asserted-by":"crossref","first-page":"200","DOI":"10.4049\/jimmunol.1100647","article-title":"Mass spectrometric characterization of circulating and functional antigens derived from piperacillin in patients with cystic fibrosis","volume":"187","author":"Whitaker","year":"2011","journal-title":"J Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib60","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/206362a0","article-title":"Penicillin allergy: the formation of the penicilloyl determinant","volume":"206","author":"Batchelor","year":"1965","journal-title":"Nature"},{"key":"10.1016\/j.jaci.2015.06.022_bib61","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/j.1365-2125.1988.tb03317.x","article-title":"A survey of the prevalence of penicillin-specific IgG, IgM and IgE antibodies detected by ELISA and defined by hapten inhibition, in patients with suspected penicillin allergy and in healthy volunteers","volume":"25","author":"Christie","year":"1988","journal-title":"Br J Clin Pharmacol"},{"key":"10.1016\/j.jaci.2015.06.022_bib62","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1084\/jem.114.6.875","article-title":"Studies on the mechanism of the formation of the penicillin antigen. III. The N-(D-alpha-benzylpenicilloyl) group as an antigenic determinant responsible for hypersensitivity to penicillin G","volume":"114","author":"Levine","year":"1961","journal-title":"J Exp Med"},{"key":"10.1016\/j.jaci.2015.06.022_bib63","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1126\/science.127.3306.1118","article-title":"Circulating antibody directed against penicillin","volume":"127","author":"Ley","year":"1958","journal-title":"Science"},{"key":"10.1016\/j.jaci.2015.06.022_bib64","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.4049\/jimmunol.155.5.2670","article-title":"Heterogeneous T cell responses to beta-lactam-modified self-structures are observed in penicillin-allergic individuals","volume":"155","author":"Brander","year":"1995","journal-title":"J Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib65","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1124\/jpet.111.190900","article-title":"Characterization of the antigen specificity of T-cell clones from piperacillin-hypersensitive patients with cystic fibrosis","volume":"341","author":"El-Ghaiesh","year":"2012","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.jaci.2015.06.022_bib66","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1124\/jpet.111.183871","article-title":"Direct evidence for the formation of diastereoisomeric benzylpenicilloyl haptens from benzylpenicillin and benzylpenicillenic acid in patients","volume":"338","author":"Meng","year":"2011","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.jaci.2015.06.022_bib67","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.tox.2005.07.015","article-title":"Immunochemical detection of flucloxacillin adduct formation in livers of treated rats","volume":"216","author":"Carey","year":"2005","journal-title":"Toxicology"},{"key":"10.1016\/j.jaci.2015.06.022_bib68","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.tox.2008.08.009","article-title":"Flucloxacillin-induced liver injury","volume":"254","author":"Andrews","year":"2008","journal-title":"Toxicology"},{"key":"10.1016\/j.jaci.2015.06.022_bib69","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/nrd3408","article-title":"Managing the challenge of chemically reactive metabolites in drug development","volume":"10","author":"Park","year":"2011","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.jaci.2015.06.022_bib70","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1002\/hep.20205","article-title":"Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxicity","volume":"39","author":"Aithal","year":"2004","journal-title":"Hepatology"},{"key":"10.1016\/j.jaci.2015.06.022_bib71","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0026-895X(25)09316-2","article-title":"Cytochrome P450 2E1 is a cell surface autoantigen in halothane hepatitis","volume":"50","author":"Eliasson","year":"1996","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.jaci.2015.06.022_bib72","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1002\/hep.26564","article-title":"Detection of anti-isoniazid and anti-cytochrome P450 antibodies in patients with isoniazid-induced liver failure","volume":"59","author":"Metushi","year":"2014","journal-title":"Hepatology"},{"key":"10.1016\/j.jaci.2015.06.022_bib73","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1124\/dmd.113.054817","article-title":"Studies on the role of metabolic activation in tyrosine kinase inhibitor-dependent hepatotoxicity: induction of CYP3A4 enhances the cytotoxicity of lapatinib in HepaRG cells","volume":"42","author":"Hardy","year":"2014","journal-title":"Drug Metab Dispos"},{"key":"10.1016\/j.jaci.2015.06.022_bib74","doi-asserted-by":"crossref","first-page":"683","DOI":"10.7326\/0003-4819-139-8-200310210-00012","article-title":"Delayed drug hypersensitivity reactions","volume":"139","author":"Pichler","year":"2003","journal-title":"Ann Intern Med"},{"key":"10.1016\/j.jaci.2015.06.022_bib75","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1111\/all.12008","article-title":"Human leukocyte antigens (HLA) associated drug hypersensitivity: consequences of drug binding to HLA","volume":"67","author":"Yun","year":"2012","journal-title":"Allergy"},{"key":"10.1016\/j.jaci.2015.06.022_bib76","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1111\/j.1365-2125.2010.03764.x","article-title":"Delayed drug hypersensitivity: models of T-cell stimulation","volume":"71","author":"Adam","year":"2011","journal-title":"Br J Clin Pharmacol"},{"key":"10.1016\/j.jaci.2015.06.022_bib77","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/S0960-894X(96)00260-0","article-title":"Synthesis and reactions of nitroso sulphamethoxazole with biological nucleophiles: implications for immune mediated toxicity","volume":"6","author":"Naisbitt","year":"1996","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.jaci.2015.06.022_bib78","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1038\/sj.bjp.0702453","article-title":"Cellular disposition of sulphamethoxazole and its metabolites: implications for hypersensitivity","volume":"126","author":"Naisbitt","year":"1999","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.jaci.2015.06.022_bib79","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1046\/j.1365-2125.1996.40110.x","article-title":"The effect of fluconazole and ketoconazole on the metabolism of sulphamethoxazole","volume":"42","author":"Gill","year":"1996","journal-title":"Br J Clin Pharmacol"},{"key":"10.1016\/j.jaci.2015.06.022_bib80","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1021\/tx900034r","article-title":"Multiple adduction reactions of nitroso sulfamethoxazole with cysteinyl residues of peptides and proteins: implications for hapten formation","volume":"22","author":"Callan","year":"2009","journal-title":"Chem Res Toxicol"},{"key":"10.1016\/j.jaci.2015.06.022_bib81","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/sj.bjp.0704074","article-title":"Antigenicity and immunogenicity of sulphamethoxazole: demonstration of metabolism-dependent haptenation and T-cell proliferation in\u00a0vivo","volume":"133","author":"Naisbitt","year":"2001","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.jaci.2015.06.022_bib82","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1021\/tx500458k","article-title":"Characterization of peroxidases expressed in human antigen presenting cells and analysis of the covalent binding of nitroso sulfamethoxazole to myeloperoxidase","volume":"28","author":"Ogese","year":"2015","journal-title":"Chem Res Toxicol"},{"key":"10.1016\/j.jaci.2015.06.022_bib83","doi-asserted-by":"crossref","first-page":"6448","DOI":"10.4049\/jimmunol.1000889","article-title":"Drug antigenicity, immunogenicity, and costimulatory signaling: evidence for formation of a functional antigen through immune cell metabolism","volume":"185","author":"Elsheikh","year":"2010","journal-title":"J Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib84","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1124\/mol.62.3.628","article-title":"Covalent binding of the nitroso metabolite of sulfamethoxazole leads to toxicity and major histocompatibility complex-restricted antigen presentation","volume":"62","author":"Naisbitt","year":"2002","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.jaci.2015.06.022_bib85","doi-asserted-by":"crossref","first-page":"5533","DOI":"10.4049\/jimmunol.178.9.5533","article-title":"Sulfamethoxazole and its metabolite nitroso sulfamethoxazole stimulate dendritic cell costimulatory signaling","volume":"178","author":"Sanderson","year":"2007","journal-title":"J Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib86","doi-asserted-by":"crossref","first-page":"531","DOI":"10.2217\/pgs.09.6","article-title":"TNF, LTA, HSPA1L and HLA-DR gene polymorphisms in HIV-positive patients with hypersensitivity to cotrimoxazole","volume":"10","author":"Alfirevic","year":"2009","journal-title":"Pharmacogenomics"},{"key":"10.1016\/j.jaci.2015.06.022_bib87","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/sj.bjp.0703845","article-title":"Influence of reduced glutathione on the proliferative response of sulfamethoxazole-specific and sulfamethoxazole-metabolite-specific human CD4+ T-cells","volume":"132","author":"Burkhart","year":"2001","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.jaci.2015.06.022_bib88","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.jaci.2009.10.031","article-title":"Stimulation of human T cells with sulfonamides and sulfonamide metabolites","volume":"125","author":"Castrejon","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib89","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.jaci.2004.07.047","article-title":"Toxic epidermal necrolysis: effector cells are drug-specific cytotoxic T cells","volume":"114","author":"Nassif","year":"2004","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib90","doi-asserted-by":"crossref","first-page":"6647","DOI":"10.4049\/jimmunol.164.12.6647","article-title":"Recognition of sulfamethoxazole and its reactive metabolites by drug-specific CD4+ T cells from allergic individuals","volume":"164","author":"Schnyder","year":"2000","journal-title":"J Immunol"},{"issue":"suppl","key":"10.1016\/j.jaci.2015.06.022_bib91","doi-asserted-by":"crossref","first-page":"S74","DOI":"10.1016\/j.jaci.2010.11.048","article-title":"Immune pathomechanism of drug hypersensitivity reactions","volume":"127","author":"Pichler","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib92","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2174\/1573395510666140407212357","article-title":"Interaction of small molecules with specific immune receptors: the p-i concept and its consequences","volume":"10","author":"Pichler","year":"2014","journal-title":"Curr Immunol Rev"},{"key":"10.1016\/j.jaci.2015.06.022_bib93","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1093\/toxsci\/kfs080","article-title":"The development of in\u00a0vitro culture methods to characterize primary T-cell responses to drugs","volume":"127","author":"Faulkner","year":"2012","journal-title":"Toxicol Sci"},{"key":"10.1016\/j.jaci.2015.06.022_bib94","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.4049\/jimmunol.1302720","article-title":"Negative regulation by PD-L1 during drug-specific priming of IL-22-secreting T cells and the influence of PD-1 on effector T cell function","volume":"192","author":"Gibson","year":"2014","journal-title":"J Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib95","doi-asserted-by":"crossref","first-page":"9959","DOI":"10.1073\/pnas.1207934109","article-title":"Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire","volume":"109","author":"Ostrov","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jaci.2015.06.022_bib96","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/nature11147","article-title":"Immune self-reactivity triggered by drug-modified HLA-peptide repertoire","volume":"486","author":"Illing","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.jaci.2015.06.022_bib97","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1038\/ni1516","article-title":"Recent advances in antigen processing and presentation","volume":"8","author":"Jensen","year":"2007","journal-title":"Nat Immunol"},{"key":"10.1016\/j.jaci.2015.06.022_bib98","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nchembio.1391","article-title":"A peptide's perspective on antigen presentation to the immune system","volume":"9","author":"Neefjes","year":"2013","journal-title":"Nat Chem Biol"},{"key":"10.1016\/j.jaci.2015.06.022_bib99","doi-asserted-by":"crossref","first-page":"e95339","DOI":"10.1371\/journal.pone.0095339","article-title":"Abacavir induced T cell reactivity from drug naive individuals shares features of allo-immune responses","volume":"9","author":"Adam","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.jaci.2015.06.022_bib100","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1021\/tx400406p","article-title":"Abacavir forms novel cross-linking abacavir protein adducts in patients","volume":"27","author":"Meng","year":"2014","journal-title":"Chem Res Toxicol"}],"container-title":["Journal of Allergy and Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S009167491500874X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S009167491500874X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T08:52:28Z","timestamp":1758790348000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S009167491500874X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8]]},"references-count":100,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["S009167491500874X"],"URL":"https:\/\/doi.org\/10.1016\/j.jaci.2015.06.022","relation":{},"ISSN":["0091-6749"],"issn-type":[{"value":"0091-6749","type":"print"}],"subject":[],"published":{"date-parts":[[2015,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity","name":"articletitle","label":"Article Title"},{"value":"Journal of Allergy and Clinical Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jaci.2015.06.022","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2015 The Authors. Published by Mosby, Inc.","name":"copyright","label":"Copyright"}]}}