Immunochemical particularities of anaphylactic reactions to compounds used in anaesthesia

Abstract

The main compounds causing anaphylactic reactions in anaesthesia are myorelaxants, opiate or barbiturate derivatives or natural allergens (latex). While the latex-derived allergens are of sizeable molecular weight and behave as regular complete allergens, most of the other compounds are low molecular weight molecules behaving as incomplete allergens or haptens. For these, the sensitization process usually encompasses direct reaction (conjugation) with cellular surface proteins (e.g. histocompatibility antigens) of an antigen-presenting cells and ensuing formation of hapten-specific IgE antibodies. Since many patients experience igE-mediated anaphylactic reactions upon first contact with a myorelaxant, a previous latent sensitivity to some cross-reactive epitope (e.g. quaternary ammonium group) must be postulated. In sensitized individuals possessing drug-specific IgE antibodies, the elicitation of anaphylactic reactions classically requires bridging on the surface of IgE loaded mast cells/basophils by allergens which are functionally at least bivalent (two or more reactive epitopes by allergen molecule). In some cases, myorelaxant molecules, chemically appearing as mirror molecules may be functionally bivalent and elicit anaphylactic reactions apparently directly. In most instances, however, when the responsible drug only contains one reactive epitope per molecule, alternative mechanisms and rapid formation of functionally polyvalent drug allergens in tissue have to be postulated in order to explain the rapid elicitation of anaphylactic reactions by molecules which appear to be immunologically monovalent in vitro. Indeed, in most instances, monovalent haptens and drugs appear to be inhibitors rather than elicitors of IgE-mediated reactions.