Antigens in Penicillin Allergy

Abstract

The present communication reveals a relationship between the epitope density of penicilloylated protein antigens and their antigenic activities in a radioimmunoassay (RIA), in passive cutaneous anaphylaxis (PCA) and in inducing antibody formation in mice. In the RIA and PCA a critical number of 2–4 penicilloyl residues per protein molecule was noted. At this level small changes in the number of substituents considerably influenced the antigenic activities. The molecular weight and the nature of the carrier proteins, myoglobin, bovine serum albumin (BSA) and dimeric BSA also affected the threshold concentration for efficient antigenic activity. The results with the RIA and PCA were significantly correlated to each other. Using penicilloylated BSA as immunizing antigen in mice it was found that an epitope number higher than 11 penicilloyl residues per protein molecule induced significant antibody formation after a single injection. Antigens with a lower degree of penicilloyl substitution were less immunogenic. An antigen carrying 0.6 penicilloyl residues per BSA molecule did not induce penicilloyl-specific antibodies even after three injections. The capacity of heavily penicilloylated proteins to induce and elicit penicillin allergy as revealed by the present results stresses the importance of limiting their presence in penicillin preparations.

Toward an in Vitro Test for the Diagnosis of Allergy to Penicillins. Synthesis, Characterization, and Use of β-Lactam and β-Lactam Metabolite Poly-l-lysines Which Recognize Human IgE Antibodies

“…It has been pointed out that a too low percent haptenization of the protein carrier lowers the effectiveness of the conjugate in eliciting Wheal-and-Flare in penicillinsensitized human subjects (34). Using penicilloylated bovine serum albumin (BSA) as the immunizing antigen in mice, it was found that an epitope number higher than 11 penicilloyl residues/protein molecule induces significant antibody formation after a single injection, whereas 0.6 penicilloyl residues/BSA molecule do not induce penicilloyl-specific antibodies (35).…”

Synthesis and characterization of a penicillin-poly(L-lysine) which is recognized by human IgE anti-penicillin antibodies

“…It has been pointed out that a too low percent haptenization of the protein carrier lowers the effectiveness of the conjugate in eliciting wheal and flare in penicillin-sensitized human subjects (20). Using penicilloylated BSA as the immunizing antigen in mice, it was found that an epitope number higher than 11 penicilloyl residues per protein molecule induces significant antibody formation after a single injection, whereas 0.6 penicilloyl residues per BSA molecule do not induce penicilloyl-specific antibodies (21).…”

Penicillin Hypersensitivity — Is Milk a Significant Hazard?: A Review

“…Numerous studies have shown that lightly substituted conjugates are very poorly, if at all, immunogenic with respect to responses specific for the hapten group. Kristofferson et al (1977), for example, found that the epitope density of a variety of penicilloyl protein conjugates had a very significant influence on immunogenicity. Conjugates carrying an average 0.6 penicilloyl residues per protein molecule failed to induce penicilloyl-specific antibody whereas those of higher levels of substitution did so readily.…”

“…The extremely low level of hapten substitution likely to be generated means that the number of even monosubstituted proteins is low and of multisubstituted, orders of magnitude lower. A minimum of disubstitution is a general requirement for a challenging antigen (Levine 1965, Kristofferson et al 1977 and, in these circumstances, is not achieved.…”