Detection and side-chain specificity of IgE antibodies to flucloxacillin in allergic subjects

Unlike studies on the antigenicity of penicillins in laboratory animals, limited information is available on the allergenicity of penicillins in man, especially with regard to fine structural allergenic differences between the many different penicillins. Inconsistent with the earlier conclusions of others, our studies suggest that side-chain structures on the penicillin molecule are the major allergenic determinants in many reactions. Immediate allergic reactions to flucloxacillin were observed in a number of patients where diagnosis was confirmed by skin testing and detection of flucloxacillin-reactive IgE antibodies. Quantitative hapten inhibition studies revealed potent inhibition by flucloxacillin and three structurally related penicillins: oxacillin, cloxacillin and dicloxacillin. Analysis of the inhibition results showed that the side-chain group of flucloxacillin, 3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolyl, is recognized by some antibodies and that the 5-methyl-3-phenyl-4-isoxazolyl group, with or without halogen substituents, accounts for the reactivity of other antibodies and for the cross-reactions seen with some other penicillins. Since it is the side-chain group that distinguishes the many different penicillins, and since the side-chain groups are recognized by IgE antibodies in many of the allergic reactions, it is becoming clear that specific assays are required for the detection of IgE antibodies to each of the different penicillins.