Der Hautarzt

, Volume 63, Issue 4, pp 299–306 | Cite as

Allergie auf Säugetierfleisch

α-Gal: Neues Epitop, neue Entität?
Leitthema

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.

Schlüsselwörter

Fleischallergie Cetuximab Galactose-α-1,3-Galactose Kohlenhydratepitope Verzögerte Anaphylaxie 

Update on meat allergy

α-Gal: a new epitope, a new entity?

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.

Keywords

Meat allergy Cetuximab Galactose-α-1,3-galactose  Carbohydrate epitope Delayed Anaphylaxis 

Literatur

  1. 1.
    Adeodoyin J, Grönlund H, Öman H et al (2007) Cat IgA, representative of new carbohydrate cross-reactive allergens. J Allergy Clin Immunol 119: 640–645CrossRefGoogle Scholar
  2. 2.
    Arkestål K, Sibanda E, Thors C et al (2011) Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-α 1,3-galactose. J Allergy Clin Immunol 127:1024–1028PubMedCrossRefGoogle Scholar
  3. 3.
    Ayuso R, Lehrer SB, Tanaka L et al (1999) IgE antibody response to vertebrate meat proteins including tropomyosin. Ann Allergy Asthma Immunol 83:399–405PubMedCrossRefGoogle Scholar
  4. 4.
    Ayuso R, Lehrer SB, Lopez M et al (2000) Identification of bovine IgG as a major cross-reactive vertebrate meat allergen. Allergy 55:348–354PubMedCrossRefGoogle Scholar
  5. 5.
    Chung CH, Mirakhur B, Chan E et al (2008) Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 358:1109–117PubMedCrossRefGoogle Scholar
  6. 6.
    Commins SP, Satinover SM, Hosen J et al (2009) Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J Allergy Clin Immunol 123:426–433PubMedCrossRefGoogle Scholar
  7. 7.
    Commins SP, Platts-Mills TA (2009) Anaphylaxis syndromes related to a new mammalian cross-reactive carbohydrate determinant. J Allergy Clin Immunol 124:652–657PubMedCrossRefGoogle Scholar
  8. 8.
    Commins SP, James HR, Kelly LA et al (2011) The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose. J Allergy Clin Immunol 127:1286–1293.e6PubMedCrossRefGoogle Scholar
  9. 9.
    Drouet M, Sabbah A, Le Sellin J et al (2001) Fatal anaphylaxis after eating wild boar meat in a patient with pork-cat syndrome. Allerg Immunol (Paris) 33:163–165Google Scholar
  10. 10.
    Duffy MS, Morris HR, Dell A et al (2006) Protein glycosylation in Parelaphostrongylus tenuis – first description of the Gal-alpha-1,3-Gal sequence in a nematode. Glycobiology 16:854–862PubMedCrossRefGoogle Scholar
  11. 11.
    Fiocchi A, Restani P, Riva E et al (1995) Meat allergy: specific IgE to BSA and OSA in atopic, beef sensitive children. J Am Coll Nutr 14:239–244PubMedGoogle Scholar
  12. 12.
    Fuentes Aparicio V, Sanchez Marcen I, Perez Montero A et al (2005) Allergy to mammal’s meat in adult life: immunologic and follow-up study. J Investig Allergol Clin Immunol 15:228–231Google Scholar
  13. 13.
    Galili U (2005) The α-Gal epitope and the anti-Gal antibody in xenotransplantation and in cancer immunotherapy. Immunol Cell Biol 83:674–686PubMedCrossRefGoogle Scholar
  14. 14.
    Grönlund H, Adedoyin J, Commins SP et al (2009) The carbohydrate glacatose-alpha-1,3-galactose is a major IgE-binding epitope on cat IgA. J Allergy Clin Immunol 123:1189–1191PubMedCrossRefGoogle Scholar
  15. 15.
    Han GD, Matsuno M, Ito G et al (2000) Meat allergy: investigation of potential allergenic proteins in beef. Biosci Biotechnol Biochem 64:1887–1895PubMedCrossRefGoogle Scholar
  16. 16.
    Hansen NL, Chandiramani DV, Morse MA et al (2010) Incidence and predictors of cetuximab hypersensitivity reactions in a North Carolina academic medical center. J Oncol Pharm Pract 0:1–6Google Scholar
  17. 17.
    Hemmer W, Mayer D, Jarisch R (2011) Fleischallergie. Allergologie 34:373–387Google Scholar
  18. 18.
    Hilger C, Kohnen M, Grigioni F et al (1997) Allergic cross-reactions between cat and pig serum albumin. Study at the protein and DNA levels. Allergy 52:179–187PubMedCrossRefGoogle Scholar
  19. 19.
    Jacquenet S, Moneret-Vautrin DA, Bihain BE (2009) Mammalian meat-induced anaphylaxis: clinical relevance of anti-galactose-alpha-1,3-galactose IgE confirmed by means of skin tests to cetuximab. J Allergy Clin Immunol 124:603–605PubMedCrossRefGoogle Scholar
  20. 20.
    Jappe U, Kreft B, Ludwig A et al (2011) Aufbau und Anwendung eines sensitiven Verfahrens zum Nachweis von IgE-Antikörpern gegen das Kohlenhydratepitop Galaktose-alpha-1,3-Galaktose. Allergo J 20:33 (Abstract)Google Scholar
  21. 21.
    Khoo KH, Nieto A, Morris HR, Dell A (1997) Structural characterization of the N-glycans from Echinococcus granulosus hydatid cyst membrane and protoscoleces. Mol Biochem Parasitol 86:237–248PubMedCrossRefGoogle Scholar
  22. 22.
    Llatser R, Polo F, De La Hoz F, Guillaumet B (1998) Alimentary allergy to pork. Crossreactivity among pork kidney and pork and lamb gut. Clin Exp Allergy 28:1021–1025PubMedCrossRefGoogle Scholar
  23. 23.
    Macher BA, Galili U (2008) The Galalpha1,3Galbeta1,4GlcNAc-R (α-Gal) epitope: a carbohydrate of unique evolution and clinical relevance. Biochim Biophys Acta 1780:75–88PubMedCrossRefGoogle Scholar
  24. 24.
    Mamikoglu B (2005) Beef, pork, and milk allergy (cross-reactivity with each other and pet allergies). Otolaryngol Head Neck Surg 133:534–537PubMedCrossRefGoogle Scholar
  25. 25.
    Nuñez R, Carballada F, Gonzalez-Quintela A et al (2011) Delayed mammalian meat-induced anaphylaxis due to galactose-α-1,3-galactose in 5 European patients. J Allergy Clin Immunol 128:1122–1124PubMedCrossRefGoogle Scholar
  26. 26.
    Plum M, Michel Y, Wallach K et al (2011) Close-up of the alpha-1,3-Gal epitope as defined by a monoclonal chimeric IgE and human serum using saturation transfer difference (STD) NMR. J Biol Chem 286:43103–43111PubMedCrossRefGoogle Scholar
  27. 27.
    Restani P, Fiocchi A, Beretta B et al (1997) Meat allergy III: proteins involved and cross-reactivity between different animal species. J Am Coll Nutr 16:383–394PubMedGoogle Scholar
  28. 28.
    Restani P, Ballabio C, Tripodi S, Fiocchi A (2009) Meat allergy. Curr Opin Allergy Clin Immunol 9:265–269PubMedCrossRefGoogle Scholar
  29. 29.
    Sabbah A. Rousseau C, Lauret MG, Drouet M (1994) The pork-cat syndrome: RAST inhibition test with Fel d 1. Allerg Immunol (Paris) 26:259–260Google Scholar
  30. 30.
    Sicherer SH, Leung DY (2010) Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2009. J Allergy Clin Immunol 125:85–97PubMedCrossRefGoogle Scholar
  31. 31.
    Simon PM, Neethling FA, Taniguchi S et al (1998) Intravenous infusion of Gal-alpha1–3-Gal oligosaccharides in baboons delays hyperacute rejection of porcine heart xenografts. Transplantation 65:346–353PubMedCrossRefGoogle Scholar
  32. 32.
    Spiro RG, Bhoyroo VD (1984) Occurrence of alpha-D-galactosyl residues in the thyroglobulins from several species. Localization in the saccharide chains of the complex carbohydrate units. J Biol Chem 259:9858–9866PubMedGoogle Scholar
  33. 33.
    Thall A, Galili (1990) Distribution of Gal alpha 1–3Galbeta1–4GlcNac residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G) as measured by a sensitive solid-phase radioimmunoassay. Biochemistry 29:3959–3965PubMedCrossRefGoogle Scholar
  34. 34.
    Van Nunen SA, O’Connor KS, Clarke LR et al (2009) An association between tick bite reactions and red meat allergy in humans. Med J Aust 190:510–511Google Scholar
  35. 35.
    Verdaguer J, Corominas M, Bas J et al (1993) IgE antibodies against bovine serum albumin in a case of eosinophilic gastroenteritis. Allergy 48:542–546PubMedCrossRefGoogle Scholar
  36. 36.
    Werfel SJ, Cooke SK, Sampson HA (1997) Clinical reactivity to beef in children allergic to cow’s milk. J Allergy Clin Immunol 99:293–300PubMedCrossRefGoogle Scholar
  37. 37.
    Wuhrer M, Grimm C, Dennis RD et al (2004) The parasitic trematode Fasciola hepatica exhibits mammalian-type glycolipids as well as Gal(β1–6)Gal-terminating glycolipids that account for cestode serological cross-reactivity. Glycobiology 14:115–126PubMedCrossRefGoogle Scholar
  38. 38.
    Wüthrich B (1996) Allergien auf Fleischeiweiße bei Erwachsenen. Allergologie 19:130–134Google Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Klinik für Dermatologie, Allergologie und VenerologieUniversität LübeckLübeckDeutschland
  2. 2.Klinische und Molekulare AllergologieForschungszentrum BorstelBorstelDeutschland

Personalised recommendations