Human leukocyte antigen-associated drug hypersensitivity

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.

► Associations between the human leukocyte antigen (HLA) and adverse drug reactions are discussed.
► We discuss evidence that interaction of HLA-B*57:01 and abacavir leads to T cell responses.
► Mechanisms of interactions between carbamazepine and HLA-B*15:02 and HLA-A*31:01 are discussed.
► We discuss evidence of other small molecules influencing peptide presentation by HLA.