Zusammenfassung
Die Assoziation von Anti-Galactose-α-1,3-Galactose (α-Gal)-IgE mit Anaphylaxie wurde erstmals nach schweren Überempfindlichkeitsreaktionen auf Cetuximab, einem chimären monoklonalen IgG-1-Antikörper zur Therapie von Kolon- sowie Plattenepithelkarzinomen des Kopfes und des Halses, beschrieben. α-Gal ist eine ubiquitäre Zuckerstruktur auf Zellen und Geweben aller Säugetiere, die keine Primaten sind. Da dieses Epitop beim Menschen nicht vorkommt, ist es für diesen hoch immunogen. α-Gal liegt auf der Fab-Portion von Cetuximab und somit auf dem murinen Anteil dieses chimären Antikörpers. Die anaphylaktischen Reaktionen auf den Therapieantikörper waren IgE-vermittelt, wobei diese IgE α-Gal-spezifisch waren. Anti-α-Gal-IgE wurden in Seren von Patienten aus dem Südosten der USA gefunden und waren reaktiv auf ein breites Spektrum von Säugetierallergenen. Aufgrund der geografischen Verteilung wurde auf Zeckenstiche und parasitäre Infektionen als mögliche Sensibilisierungswege untersucht. Anti-α-Gal-IgE scheinen pathophysiologische Bedeutung bei Allergien auf rotes Fleisch/Innereien sowie für das „Cat-Pork-Syndrom“ zu haben. Zusätzlich fiel auf, dass Anti-α-Gal-IgE mit der ungewöhnlichen Form einer verzögerten Anaphylaxie, welche 3–6 h nach dem Genuss von Säugetierfleisch (Rind, Schwein oder Lamm) auftritt, assoziiert sind, ein Phänomen, das pathophysiologisch noch ungeklärt ist. Viele dieser Patienten hätten zudem mit konventionellen Pricktestextrakten nicht diagnostiziert werden können.
Abstract
The association between the carbohydrate galactose-[alpha]-1,3-galactose (α-Gal) and anaphylaxis was first documented after severe hypersensitivity reactions to cetuximab, a chimeric mouse-human IgG1 monoclonal antibody approved for targeted therapy of carcinomas of colon, as well as of the head and neck region. α-Gal is a ubiquitous glycan moiety expressed on cells and tissue of non-primate mammals. Since this epitope is not expressed in humans, it is very immunogenic for them. α-Gal is located on the Fab portion of cetuximab and thus on the murine part of the chimera. The anaphylactic reactions to the antibody were mediated by IgE specific for α-Gal. Anti-α-Gal-IgE were first detected in sera of patients from the southeastern U.S. and reacted with a wide range of mammalian allergens. The geographic distribution prompted investigations of sensitization routes apart from the ingestion of red meat, such as tick bites und parasitic infections. Anti-α-Gal-IgE seems to be of clinical relevance for allergy to red meat and for the pork-cat syndrome. It is also associated with a novel form of delayed anaphylaxis, which appears more than 3 hours following the ingestion of red meat (beef, pork and lamb), a phenomenon which is still to be elucidated. For most of these patients conventional skin prick tests with commercial reagents proved insufficient for diagnosis.
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Jappe, U. Allergie auf Säugetierfleisch. Hautarzt 63, 299–306 (2012). https://doi.org/10.1007/s00105-011-2266-y
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DOI: https://doi.org/10.1007/s00105-011-2266-y