Penicillin allergy and the heterogenous immune responses of man to benzylpenicillin.

A comparative study of the formation of chemically reactive drug metabolites by human liver microsomes.

“…According to the hapten hypothesis of drug hypersensitivity, drugs may become immunogenic once conjugated to a macromolecular carrier . This hypothesis was evolved largely from studies with penicillin antibiotics, which contain a ,-lactam nucleus that has inherent chemical reactivity towards nucleophilic groups on proteins (Levine et al, 1966). For a number of other drugs associated with hypersensitivity reactions in man it has been assumed that drug haptens are formed from chemically reactive metabolites, rather than parent drug but there is little or no experimental evidence for such a mechanism in most cases 14 N. R. Kitteringham et al…”

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.

“…A wide variety of methods have been used to measure serum antibodies directed against penicillin (de Weck, 1983) including the red celllinked antigen-antiglobulin reaction , haemagglutination (Thiel et al, 1964;Levine et al, 1966;Spath et al, 1971), radioimmunoassay (Lee et al, 1986), radioallergosorbent test (Kraft & Wide, 1976) However, because criteria for positive identification of drug-specific antibody activity are often poorly defined, it is difficult to determine objectively the prevalence of antibodies in patient and control groups in previous studies.…”

Hapten immunology and allergic reactions in humans

“…In addition, a short time later it was found that the antibodies present in the serum of individuals receiving pencillin were not directed toward penicillin itself, but to various breakdown products of penicillin, especially the penicilloyl group (13,28). Bernard Levine and his colleagues independently drew very similar conclusions (29)(30)(31)(32), and out of the work of the 2 laboratories practical procedures for the everyday diagnosis of human penicillin allergy were developed.…”

“…The pattern of allergic reactivity in penicillin allergy is actually rather complex in that penicillin is not only subject to direct aminolysis by protein lysyl groups to form penicilloyl groups but also gives rise to a variety of breakdown products with protein reactivity, including penicillenic acid, penicillamine, and penicilloic acid. Virtually everyone who is treated with penicillin develops an immune response to the penicilloyl group (8,28) but in addition antibodies are sometimes demonstrable to penicillenate (or its oxidation products), penicillamine, penamaldoyl, penicilloaldehyde, polymers of 6-aminopenicillanic acid, or other poorly characterized determinants (27,28,(32)(33)(34)(35). All of the penicillin determinants that have been identified have the capability of forming covalent bonds with proteins.…”