Allotype specific interactions of drugs and HLA molecules in hypersensitivity reactions.
It is hypothesised that associations between adverse drug reactions and specific alleles of the human leukocyte antigens arise due to specific interactions between the human leukocyte antigen molecules and the causative drug that stimulate immune responses targeting drug exposed tissues. To date this has only been definitively demonstrated for abacavir, an antiretroviral that causes a systemic adverse drug reaction, abacavir hypersensitivity syndrome, solely in HLA-B*57:01+individuals. Whilst this has informed the modification of abacavir to remove immunogenicity, there remains an imperative to define other interactions between drugs and specific HLA in order to understand the scope of interactions that can drive T cell mediated drug hypersensitivity. Here we review the current state of understanding of these interactions.
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Victoria, Australia. Electronic address: patricia.illing@monash.edu.
Patricia T
PT
Illing
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Victoria, Australia.
Nicole A
NA
Mifsud
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Victoria, Australia.
Anthony W
AW
Purcell
D000483:Alleles; D015224:Dideoxynucleosides; D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D015235:HLA-B Antigens; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology*; D000099227:Abacavir
D015224:Dideoxynucleosides; D006680:HLA Antigens; D015235:HLA-B Antigens; D000099227:Abacavir; C484830:HLA-B*57:01 antigen