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.
Bugelski
Peter J
PJ
Director of Experimental Pathology, Department of Toxicology and Investigational Pharmacology, Centocor Inc., 200 Great Valley Parkway, Malvern, Pennsylvania 19355, USA. pbugelsk@cntus.jnj.com
D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D007125:Immunogenetics; D018448:Models, Immunological