Human leukocyte antigens and drug hypersensitivity. 2007

Wen-Hung Chung, and Shuen-Iu Hung, and Yuan-Tsong Chen
Molecular Medicine Program of Taiwan International Graduate Program, Institute of Biomedical Sciences, Academia Sinica and School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.

OBJECTIVE The present article reviews the recent literature on the identification of human leukocyte antigen (HLA) alleles as major susceptible genes for drug hypersensitivity and discusses the clinical implications. RESULTS Several recent studies have reported strong genetic associations between HLA alleles and susceptibility to drug hypersensitivity. The genetic associations can be drug specific, such as HLA-B*1502 being associated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), HLA-B*5701 with abacavir hypersensitivity and HLA-B*5801 with allopurinol-induced severe cutaneous adverse reactions. A genetic association can also be phenotype-specific, as B*1502 is associated solely with carbamazepine-SJS/TEN, and not with either maculopapular eruption or hypersensitivity syndrome. Furthermore, a genetic association can also be ethnicity specific; carbamazepine-SJS/TEN associated with B*1502 is seen in south-east Asians but not in whites, which may be explained by the different allele frequencies. CONCLUSIONS The strong genetic association suggests a direct involvement of HLA in the pathogenesis of drug hypersensitivity when the HLA molecule presents an antigenic drug for T cell activation. The high sensitivity/specificity of some markers provides a plausible basis for developing tests to identify individuals at risk for drug hypersensitivity. Application of HLA-B*1502 genotyping as a screening tool before prescribing carbamazepine could be a valuable tool in preventing carbamazepine-induced SJS/TEN in south-east Asian countries.

UI MeSH Term Description Entries
D010597 Pharmacogenetics A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION). Pharmacogenomics
D002220 Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties. Amizepine,Carbamazepine Acetate,Carbamazepine Anhydrous,Carbamazepine Dihydrate,Carbamazepine Hydrochloride,Carbamazepine L-Tartrate (4:1),Carbamazepine Phosphate,Carbamazepine Sulfate (2:1),Carbazepin,Epitol,Finlepsin,Neurotol,Tegretol
D003875 Drug Eruptions Adverse cutaneous reactions caused by ingestion, parenteral use, or local application of a drug. These may assume various morphologic patterns and produce various types of lesions. Dermatitis Medicamentosa,Dermatitis, Adverse Drug Reaction,Maculopapular Drug Eruption,Maculopapular Exanthem,Morbilliform Drug Reaction,Morbilliform Exanthem,Drug Eruption,Drug Eruption, Maculopapular,Drug Eruptions, Maculopapular,Drug Reaction, Morbilliform,Drug Reactions, Morbilliform,Eruption, Drug,Eruption, Maculopapular Drug,Eruptions, Drug,Eruptions, Maculopapular Drug,Exanthem, Maculopapular,Exanthem, Morbilliform,Exanthems, Maculopapular,Exanthems, Morbilliform,Maculopapular Drug Eruptions,Maculopapular Exanthems,Morbilliform Drug Reactions,Morbilliform Exanthems,Reaction, Morbilliform Drug,Reactions, Morbilliform Drug
D004342 Drug Hypersensitivity Immunologically mediated adverse reactions to medicinal substances used legally or illegally. Allergy, Drug,Hypersensitivity, Drug,Drug Allergy,Allergies, Drug,Drug Allergies,Drug Hypersensitivities,Hypersensitivities, Drug
D006680 HLA Antigens Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases. Human Leukocyte Antigen,Human Leukocyte Antigens,Leukocyte Antigens,HL-A Antigens,Antigen, Human Leukocyte,Antigens, HL-A,Antigens, HLA,Antigens, Human Leukocyte,Antigens, Leukocyte,HL A Antigens,Leukocyte Antigen, Human,Leukocyte Antigens, Human
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000493 Allopurinol A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms. Allohexal,Allohexan,Alloprin,Allopurin,Allorin,Allpargin,Allural,Apulonga,Apurin,Atisuril,Bleminol,Caplenal,Capurate,Cellidrin,Embarin,Foligan,Hamarin,Jenapurinol,Lopurin,Lysuron,Milurit,Milurite,Novopurol,Pan Quimica,Progout,Pureduct,Purinol,Remid,Rimapurinol,Roucol,Suspendol,Tipuric,Uribenz,Uridocid,Uripurinol,Urosin,Urtias,Xanthomax,Xanturic,Zygout,Zyloprim,Zyloric
D013262 Stevens-Johnson Syndrome Rare cutaneous eruption characterized by extensive KERATINOCYTE apoptosis resulting in skin detachment with mucosal involvement. It is often provoked by the use of drugs (e.g., antibiotics and anticonvulsants) or associated with PNEUMONIA, MYCOPLASMA. It is considered a continuum of Toxic Epidermal Necrolysis. Drug-Induced Stevens Johnson Syndrome,Drug-Induced Stevens-Johnson Syndrome,Epidermal Necrolysis, Toxic,Lyell's Syndrome,Mycoplasma-Induced Stevens Johnson Syndrome,Mycoplasma-Induced Stevens-Johnson Syndrome,Nonstaphylococcal Scalded Skin Syndrome,Scalded Skin Syndrome, Nonstaphylococcal,Stevens Johnson Syndrome Toxic Epidermal Necrolysis,Stevens Johnson Syndrome Toxic Epidermal Necrolysis Spectrum,Stevens-Johnson Syndrome Toxic Epidermal Necrolysis,Stevens-Johnson Syndrome Toxic Epidermal Necrolysis Spectrum,Toxic Epidermal Necrolysis,Toxic Epidermal Necrolysis Stevens Johnson Syndrome,Toxic Epidermal Necrolysis Stevens Johnson Syndrome Spectrum,Toxic Epidermal Necrolysis Stevens-Johnson Syndrome,Toxic Epidermal Necrolysis Stevens-Johnson Syndrome Spectrum,Drug Induced Stevens Johnson Syndrome,Drug-Induced Stevens-Johnson Syndromes,Epidermal Necrolyses, Toxic,Lyell Syndrome,Lyell's Syndromes,Mycoplasma Induced Stevens Johnson Syndrome,Necrolyses, Toxic Epidermal,Necrolysis, Toxic Epidermal,Stevens Johnson Syndrome,Stevens-Johnson Syndrome, Drug-Induced,Stevens-Johnson Syndrome, Mycoplasma-Induced,Stevens-Johnson Syndromes, Drug-Induced,Syndrome, Lyell's,Syndrome, Mycoplasma-Induced Stevens-Johnson,Syndromes, Lyell's,Toxic Epidermal Necrolyses
D015224 Dideoxynucleosides Nucleosides that have two hydroxy groups removed from the sugar moiety. The majority of these compounds have broad-spectrum antiretroviral activity due to their action as antimetabolites. The nucleosides are phosphorylated intracellularly to their 5'-triphosphates and act as chain-terminating inhibitors of viral reverse transcription. 2',3'-Dideoxynucleosides,Dideoxyribonucleosides,ddNus,2',3' Dideoxynucleosides
D015235 HLA-B Antigens Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes. Antigens, HLA-B,HLA-B Antigen,HLA-B,Antigen, HLA-B,Antigens, HLA B,HLA B Antigen,HLA B Antigens

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