Summary
The results revealed the presence of high molecular weight impurities in commercially available penicillins, measured with a radioimmuno assay. The impurities had penicilloyl specificity and induced antibody formation in mice when the contaminated penicillin was administered in 50 mg/kg body weight daily for ten day periods with a 20 to 30 day interval. Penicillin of high purity similarly administered produced very few antibodies. Furthermore, experimentally contaminated penicillin given according to the same schedule caused IgE antibody formation against the penicilloyl moiety, while pure penicillin did not. These findings were explained by the weak immunogenicity of isologous penicilloylated serum albumin in rabbits both regarding the IgE and the IgG/IgM antibody formation compared to the immunogenicity of heterologous bovine serum albumin similarly penicilloylated.
Zusammenfassung
Die mit dem Radioimmunoassay gewonnenen Untersuchungsergebnisse deckten die Anwesenheit von hochmolekularen Verunreinigungen in kommerziell erhältlichen Penicillinen auf. Diese Verunreinigungen waren Penicilloyl-artige Substanzen und induzierten bei Mäusen die Bildung von Antikörpern, wenn das kontaminierte Penicillin in Dosen von 50 mg/kg Körpergewicht und Tag zehn Tage lang in Zeitintervallen von 20 bis 30 Tagen verabreicht wurde. Penicillin von hohem Reinheitsgrad, das in ähnlicher Weise gegeben wurde, verursachte nur eine geringe Antikörperbildung. Darüber hinaus führte experimentell kontaminiertes Penicillin, das nach demselben Schema verabreicht wurde, zur Bildung von IgE Antikörpern gegen den Penicilloyl-Anteil, während reines Penicillin das niemals tat. Diese Befunde wurden durch die im Vergleich zur Immunogenität von in ähnlicher Weise an heterologes Rinder-Serumalbumin gebundenem Penicilloyls, schwache Immunogenität von an homologem Serumalbumin gebundenes Penicilloyl im Kaninchen, sowohl bezüglich der IgE-als auch der IgG/IgM-Antikörper-Bildung, erklärt.
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Literatur
Idøse, O., Guthe, T., Willcox, R. R., Weck, A. L. Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bull. W. H. O. 38 (1968) 159–188.
Croydon, E. A. P., Wheeler, A. W., Grimshaw, J. J., Atkins, W., Cowan, M. A., Geddes, A. M., Jain, S., Yassa, J. G., Beveridge, G. W., Murdoch, J. Mc. C., Pullen, H., Rowell, N. R., Steenson, J. Prospective study of ampicillin rash — report of a collaborative study group. Br. Med. J. 1 (1973) 7–9.
Kristofferson, A., Ahlstedt, S., Pettersson, E., Svärd, P. O. Antigens in penicillin allergy. I. A radioimmunoassay for detection of penicilloylated protein contaminants in penicillin preparations. Int. Arch. Allergy Appl. Immun. 55 (1977) 13–22.
Parker, C. W.: Conjugation of penicillin and its derivatives: In:Williams, Chase, Methods in immunology and immunochemistry, Vol. I. New York, London, 1976 p. 133–143.
Ahlstedt, S., Kristofferson, A., Pettersson, E.: Antigens in penicillin allergy. III. Antigen and antibody levels in mice treated with pure and contaminated penicillins. Int. Arch. Allergy Appl. Immun. (1978) in press.
Kristoffersson, A., Ahlstedt, S., Hall E.: Antigens in penicillin allergy IV. IgE antibody response in mice after daily treatment with pure or contaminated penicillin. Int. Arch. Allergy Appl. Immun. (in press).
Rodell, A. K., Ahlstedt, S., Olsson, T. K., Svärd, P. O. Formation of homocytotropic antibodies with penicilloyl specificity in the rabbit. Int. Arch. Allergy Appl. Immun. 51 (1976) 156–167.
Ahlstedt, S., Kristoffersson, A., Pettersson, E., Svärd, P. O. The binding properties of rabbit antibodies against various penicillins as studied by immunoprecipitation, indirect haemagglutination and radiometric immunoassay. Int. Arch. Allergy Appl. Immun. 51 (1976) 145–155.
Batchelor, F. R., Dewdney, J. M., Feinberg, J. G., Weston, R. D.: A penicilloylated protein impurity as a source of allergy to benzylpenicillin and 6-aminopenicillanic acid. Lancet I (1967) 1175–1177.
Ottens, H., de Haan, E., Sengers, C. H. J. A search for high molecular impuritis in penicillin G. Int. Arch. Allergy Appl. Immun. 41 (1971) 575–591.
Weidenmüller, H.-L., Ziegler, W. On the proteinaccous impurity of penicillin. Arzneim.-Forsch. 4 (1970) 585–586.
Bundgaard, H. Penicillin allergy. Kinetics of penicilloylation of serum albumin by various penicillins. Acta Pharm. Suec. 14 (1977) 391.
Levine, B. B., Ovary, Z. Studies on the mechanism of the formation of the penicillin antigen. III. The N-(D-α-benzylpenicilloyl) group as an antigenic determinant responsible for hypersensitivity to penicillin G. J. Exp. Med. 114 (1961) 875–904.
Ahlstedt, S., Svärd, P. O., Kristofferson, A., Ekström, B., Sjöberg, B., Örtengren, B.: New insights into antigens in penicillin allergy. Crit. Rev. Toxicol. (In press).
Brummer, E. Immunoglobulin E antibody formation in response to homologous rabbit albumin heavily substituted with dinitropenol: Effect of adjuvant. Infect. Immun. 11 (1975) 955–961.
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Ahlstedt, S., Kristofferson, A. Experimental evidence of a decreased incidence of penicillin allergy through use of pure penicillins. Infection 7 (Suppl 5), S499–S502 (1979). https://doi.org/10.1007/BF01659783
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DOI: https://doi.org/10.1007/BF01659783