STUDIES OF THE SPECIFICITIES OF IGE ANTIBODIES FOUND IN SERA FROM SUBJECTS WITH ALLERGIC REACTIONS TO PENICILLINS

Penicillins are immunogenic when administered to humans and in some in stances they can also be allergenic, inducing specific IgE antibodies. Whilst the major haptenic group, the penicilloyl, is well characteris ed, less is known about the relative importance of the different parts of the structure for antibody binding and how this can influence the specificity of patients response. In order to investigate this further , sera from subjects who had suffered an IgE-mediated reaction to peni cillins were studied using the radioallergosorbent test (RAST) and RAS T inhibition. The assays employed reagents related to the penicillins causing the reaction. Using 173 sera, positive RAST results were only found with reagents based on benzyl penicillin (BP) and amoxicillin (A X). Fifty-three positive sera were selected for further studies and ca tegorized into three groups: (A) sera only RAST positive to AX, (B) se ra only positive to BP and (C) sera positive to both penicillins. RAST inhibition studies were then carried out using monomeric penicilloyl conjugates and compounds representing parts of the penicilloyl structu res of BP and AX. For all three groups, monomeric penicilloyl conjugat es were the most efficient inhibitors but there were differences for t he other compounds. Group A sera were also inhibited by the side chain of amoxicillin, whereas group B sera were poorly inhibited by all oth er inhibitors. Group C sera showed two patterns of inhibition, both co nsistent with their more cross-reactive profile. Some group C sera wer e similar to group B, showing inhibition with monomeric penicilloyl co njugates only, whilst others were similar to group A showing inhibitio n with side-chain-related compounds, although in these cases all the s ide chain compounds inhibited all the assays. We conclude that in sera from patients allergic to penicillins, IgE antibodies of different sp ecificities can be found reflecting the involvement of the penicillins in inducing the allergic reaction. Detailed inhibition analysis indic ates that two main groups of antibodies can be distinguished: one wher e the side chain contributes a unique specificity to the antigen bindi ng site and in which they are positive to AX, and another where most o f the structure is required for optimal inhibition. However, a conside rable variation in the pattern of recognition of the antigenic determi nant was seen. No coexisting antibodies of different specificities wer e detected in the same patient.