Hypersensitivity to Penicillenic Acid Derivatives in Human Beings With Penicillin Allergy

Abstract

In this paper we are concerned with the following question: Are the benzylpenicilloyl and the benzylpenicillenate groups specific determinants of allergic reactions to benzylpenicillin in man? 1 Since simple organic molecules combine covalently with proteins as a preliminary step in the induction of the hypersensitive state, it seems clear that penicillin itself, which is incapable of reacting in the required manner with protein, must be regarded as a precursor of some derivative which possesses this necessary capacity. Penicillenic acid could well be the derivative in question since it forms spontaneously and readily from penicillin in neutral aqueous solution and is a highly reactive molecule capable of coupling with protein sulfhydryl and amino groups forming S-penicillenate and N-penicilloyl substituents, respectively (1, 2). Moreover, penicillenate-and penicilloyl-protein conjugates, prepared in vitro and injected into experimental animals, have been shown to be potent antigens (1). Elicitation of whealand-erythema responses in humans with well documented histories of penicillin hypersensitivity seemed to offer the most direct means for evaluating the determinant role of penicillenate and penicilloyl groups. Our preliminary studies in man using penicilloyl-and penicillenate-proteins as test reagents showed an encouraging correlation between positive wheal-and-erythema responses and a *

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

“…The materials were nonirritating as used. Previous studies showed these reagents and the 2 IgG antibodies are 7 S (molecular weight about 160,-000), and IgM antibodies are 19 S (molecular weight about 1,000,000). Skin-sensitizing antibodies appear to be neither IgM nor IgG antibodies.…”

Studies on Artificial Antigens

“…On the evidence presented, the role of a high degree of conjugation decreasing antigenicity might also explain the absence of immune response observed by these investigators. The antigenicity in guinea pigs of DNP conjugates of polylysine averaging only 20 lysyl residues warrants caution in the use of such polymers conjugated with benzyl penicilloyl in human penicillin sensitivity studies as it has been suggested (25).…”

Fixation of penicilloyl groups to albumin and appearance of anti-penicilloyl antibodies in penicillin-treated patients.

“…Furthermore, many authors have long suspected BPO groups to be involved in the pathogenesis of penicillin allergy (6)(7)(8).…”