A survey of the prevalence of penicillin‐specific IgG, IgM and IgE antibodies detected by ELISA and defined by hapten inhibition, in patients with suspected penicillin allergy and in healthy volunteers.

Abstract

1. IgG, IgM and IgE anti‐benzylpenicilloyl (BPO) antibody activities were determined by enzyme‐linked immunosorbent assay (ELISA) in sera from 100 patients who claimed to be allergic to penicillin, and from 50 healthy volunteers. Continuous frequency distributions for all three classes of anti‐BPO antibody, defined as differential binding (delta OD) to BPO‐human serum albumin (HSA) and HSA, were obtained for both groups. 2. For IgM and IgE classes the anti‐BPO activities were slightly but statistically significantly higher in the patient group compared with the volunteer group. 3. Hapten inhibition ELISAs were performed to confirm specificity for the BPO determinant. On the basis of antibody activities (delta OD values) greater than or equal to 0.3 and 50% inhibition of binding in the presence of 100 micrograms ml‐1 BPO‐caproate, BPO‐specific IgG antibody was identified in 4/100 of the patients' sera and in 1/50 of the volunteers' sera; BPO‐specific IgM was identified in 7/100 patients' sera and 1/50 volunteers' sera; and BPO‐specific IgE in 5/100 patients' sera and 1/50 volunteers' sera. 4. Not all sera with differential antibody binding to BPO‐HSA/HSA were inhibited by the BPO hapten. Hence, hapten inhibition assays are essential for the unambiguous demonstration of drug specific antibodies.

Idiosyncratic Adverse Drug Reactions: Current Concepts

“…They influence the T-cell response by enhancing antigen capture and delivery by modulating processing pathways, thus suppressing the generation of dominant antigenic determinants and by preventing processing (Watts and Lanzavecchia, 1993). We and others have used drug-protein conjugates to detect anti-drug antibodies in certain tolerant and allergic patients (de Haan et al, 1986;Christie et al, 1988;Daftarian et al, 1995;Torres et al, 1997). However, the dynamics of the drug antigen-specific humoral response and the kinetics of antibody production have not been defined.…”

“…It is possible that this pathway of drug-specific T-cell activation is an in vitro artifact mimicking the action of processed haptenmodified peptides. Importantly, several groups have used b-lactam albumin conjugates to detect antidrug antibodies in tolerant and allergic patients (de Haan et al, 1986;Christie et al, 1988;Torres et al, 1997). Thus, hapten theory is thought to accurately describe the drug-specific activation of B cells that recognize protein antigens directly through their B cell receptor.…”

Immunogenicity of Amodiaquine in the Rat

“…This is, therefore, an expression of specific (amodiaquine inhibitable) antibody. Thus we have adopted the criterion, similar to previous studies [11], that a AOD>0.2 at a serum dilution of 1 in 30 designates a positive re sponse.…”

Disposition and Immunogenicity of Penicillin in the Rabbit

“…Penicillin has become accepted as the classical ex ample of drug-induced hypersensitivity and has been used as a model for understanding hypersensitivity in man, because of its ability to induce the formation of drug-specific antibodies in patients [1]. In accordance with the hapten hypothesis of drug hypersensitivity, it has been shown that the induction of a drug-specific antibody response is dependent upon irreversible binding of penicillin to macromolecular carriers.…”

“…The immune re sponse was clearly dose-dependent, since an intra muscular dose of 27 pmol/kg did not ellicit a detec table antibody response. The IgG anti-BPO response was measured by a specific and sensitive ELISA and defined by hapten inhibition, which has been shown to be essential for the definition of a drug-specific re sponse in humans [1] and rats [2]. The immune re sponse to BP in the rabbit showed considerable inter animal variation ( fig.…”