STRUCTURE-ACTIVITY STUDIES ON DRUG-INDUCED ANAPHYLACTIC REACTIONS

As a result of recent research and development, an expanding range of in vitro assays for the detection of drug-reactive IgE antibodies is now available for the diagnosis of individual drug allergies. Continuing immunochemical studies on drugs implicated in allergic reactions via further development of specific immunoassays and production of drug-protein conjugates will allow us to build up a picture of the repertoire of drug and drug-derived B-cell allergenic determinant structures and to identify and predict cross-reactivities. Although we have made good progress in identifying some drug B-cell determinants, we remain ignorant of drug T-cell determinants and, indeed, of the nature of T-cell recognition of all nonpeptide molecules. Demonstration that drugs specifically recognize T-cells from drug-allergic patients may reveal associations with HLA phenotypes, the nature and location of interaction between drug and MHC molecules, and the nature and identity of drug or drug-derived T-cell antigens. A knowledge of the molecular nature of T-cell determinants inducing allergic responses is fundamental to therapeutic attempts to modulate these deleterious reactions. The possibility now exists for the allergenic screening of drugs as part of their toxicological evaluation, and identification of allergenic structures on drugs also has implications for the testing of the allergenic activity and sensitizing potential of other chemicals in our environment. Obvious and important areas for the application of our methods and findings are the pharmaceutical and cosmetic industries. © 1994, American Chemical Society. All rights reserved.