T cell-mediated hypersensitivity reactions to drugs.
The immunological mechanisms driving delayed hypersensitivity reactions (HSRs) to drugs mediated by drug-reactive T lymphocytes are exemplified by several key examples and their human leukocyte antigen (HLA) associations: abacavir and HLA-B*57:01, carbamazepine and HLA-B*15:02, allo-purinol and HLA-B*58:01, and both amoxicillin-clavulanate and nevirapine with multiple class I and II alleles. For HLA-restricted drug HSRs, specific class I and/or II HLA alleles are necessary but not sufficient for tissue specificity and the clinical syndrome. Several models have been proposed to explain the immunopathogenesis of severe T cell-mediated drug HSRs, and our increased understanding of the risk factors and mechanisms involved in the development of these reactions will further the development of sensitive and specific strategies for preclinical screening that will lead to safer and more cost-effective drug design.
Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, 6150; email: e.phillips@iiid.com.au.
Rebecca
R
Pavlos
Simon
S
Mallal
David
D
Ostrov
Soren
S
Buus
Imir
I
Metushi
Bjoern
B
Peters
Elizabeth
E
Phillips
D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology*; D063926:Drug Hypersensitivity Syndrome / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology*; D013262:Stevens-Johnson Syndrome / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D006680:HLA Antigens
Stevens-Johnson syndrome; altered peptide; human leukocyte antigen; major histocompatibility complex; pharmacogenomics; toxic epidermal necrolysis