Drug hypersensitivity and human leukocyte antigens of the major histocompatibility complex.
The human leukocyte antigen (HLA) genes are the most polymorphic in the human genome and are critical in regulating specific immunity, hence their historical discovery as "immune response" genes. HLA allotypes are also implicated in unwanted immune reactions, including drug hypersensitivity syndrome, in which small therapeutic drugs interact with antigenic peptides to drive T cell responses restricted by host HLA. Abacavir, allo-purinol, and carbamazepine are three commonly used drugs that cause a T cell-mediated hypersensitivity that is HLA linked, with each drug exhibiting striking specificity for presentation by defined HLA allotypes. Recent findings have begun to unearth the mechanistic basis for these HLA associations, and here we review recent advances in the field of HLA-associated drug hypersensitivities.
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia. mandvi@unimelb.edu.au
Mandvi
M
Bharadwaj
Patricia
P
Illing
Alex
A
Theodossis
Anthony W
AW
Purcell
Jamie
J
Rossjohn
James
J
McCluskey
D000483:Alleles; D000493:Allopurinol / Q000009:adverse effects; D002220:Carbamazepine / Q000009:adverse effects; D015224:Dideoxynucleosides / Q000009:adverse effects; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000099227:Abacavir
D000493:Allopurinol; D002220:Carbamazepine; D015224:Dideoxynucleosides; D006680:HLA Antigens; D000099227:Abacavir