title: Human leukocyte antigen-associated drug hypersensitivity.
abstract: A growing number of associations between adverse drug reactions and alleles of the human leukocyte antigen (HLA) genes are now known. Although several models have been proposed to explain these associations, an underlying molecular basis has only recently been described. The associations between HLA-B*57:01 and abacavir hypersensitivity syndrome, and HLA-B*15:02 and carbamazepine-induced bullous skin disease have provided new insights into the mechanism associated with hypersensitivity reactions to these drugs. Here we discuss recent evidence that small molecules can interact with specific HLA to distort self-peptide presentation leading to autoimmune-like drug hypersensitivities that potentially provide clues to the mechanisms underlying other immunopathologies.
authors.affiliation: Department of Microbiology & Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Patricia T
authors.initials: PT
authors.lastname: Illing
authors.forename: Julian P
authors.initials: JP
authors.lastname: Vivian
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D017951:Antigen Presentation / Q000187:drug effects; D001324:Autoantigens / Q000378:metabolism; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy*; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D000927:Anticonvulsants; D001324:Autoantigens; D002220:Carbamazepine; D015224:Dideoxynucleosides; D006680:HLA Antigens; D010446:Peptide Fragments; D000099227:Abacavir