Predictive drug allergy testing: an alternative viewpoint.
T- and B-cells recognise drugs when bound as haptens to carrier molecules. Recent studies suggest that drugs might also bind in a non-covalent form to MHC-peptide complexes and T cell receptors, and are thereby able to stimulate T cells. This has, however, only been shown for drug-specific T cell clones. Functional analysis revealed that drug-reactive T cells secrete high amounts of IL-5 and are cytotoxic. Cytotoxicity is mediated by drug-specific CD4(+) and CD8(+) cells and, as revealed by the immunohistochemical analysis of drug-induced exanthems, might be involved in the killing of keratinocytes thus explaining the drug-induced exanthem. Further work is needed to clarify the type and exact location of the rather labile drug binding to MHC and T cell receptors, and to evaluate what drug allergies might be caused by such an unusual presentation and immune stimulation. This new model as well as findings from the analysis of clinical drug allergies may have major implications on how to test and predict the allergenic potential of drugs. A change and expansion of currently performed test procedures is required to predict the allergenic potential of drugs.
Pichler
W J
WJ
Division of Allergology, Clinic for Rheumatology and Clinical Immunology/Allergology Inselspital, University of Bern, CH 3010, Bern, Switzerland. werner.pichler@insel.ch
D000826:Animal Testing Alternatives; D000818:Animals; D002478:Cells, Cultured; D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D064420:Drug-Related Side Effects and Adverse Reactions; D006680:HLA Antigens / Q000502:physiology; D006241:Haptens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011237:Predictive Value of Tests; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D006680:HLA Antigens; D006241:Haptens; D004364:Pharmaceutical Preparations; D011948:Receptors, Antigen, T-Cell