Genetic aspects of immune-mediated adverse drug effects.

Adverse drug effects (ADEs) are of great importance in medicine and account for up to 5% of all hospital admissions. ADEs can arise from several mechanisms and a wide range of drugs can cause immune-mediated ADEs (IMADEs). For a drug to elicit an IMADE, it must be both immunogenic (that is, able to sensitize the immune system) and antigenic (that is, able to evoke a response from a sensitized immune system). Unlike protein therapeutics, small-molecule drugs (or xenobiotics) are usually neither immunogenic nor antigenic. IMADEs are therefore the result of complex interactions between drug-metabolizing enzymes, immune sensitization and immune effectors. The genetic aspects of this interplay are discussed in this review.