Skip to main content
SpringerLink
Log in

Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal)

  • ANAPHYLAXIS AND DRUG ALLERGY (P LIEBERMAN AND S SPECTOR, SECTION EDITORS)
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal. In instances where the triggering allergen is not known, establishing the etiology of anaphylaxis is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody (Ab) response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), that has been associated with two distinct forms of anaphylaxis: (1) immediate onset anaphylaxis during first exposure to intravenous cetuximab, and (2) delayed onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g., beef and pork). The results of our studies strongly suggest that tick bites are a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the southern, eastern and central United States. Patients with IgE Ab to alpha-gal continue to emerge and, increasingly, these cases involve children. This IgE Ab response cross-reacts with cat and dog but does not appear to pose a risk for asthma; however, it may impair diagnostic testing in some situations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

alpha-gal:

galactose-α-1,3-galactose

Ab:

antibody

References

Papers of particular interest, published recently, have been highlighted as: •Of importance ••Of major importance

  1. Commins SP, Satinover SM, Hosen J, et al. 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. 2009;123:426–33.

    Article  PubMed  CAS  Google Scholar 

  2. • Commins SP, Kelly LA, Rönmark E, et al. Galactose-α-1,3-galactose-specific IgE is associated with anaphylaxis but not asthma. Am J Respir Crit Care Med. 2012;185:723–30. Data are presented that show the specific IgE Ab response can contribute to total serum IgE and preliminary evidence that the alpha-gal epitope is not airborne in homes with or without cats or dogs, under conditions where large quantities of Fel d 1 and Can f 1 can be detected. The authors concluded that the association between IgE Ab and asthma relates to IgE Ab for protein allergens that are inhaled.

    Article  PubMed  CAS  Google Scholar 

  3. Mullins RJ, James H, Platts-Mills TA, Commins S. 2012. J Allergy Clin Immunol. 2012;129:1334–42.e1331.

    Article  PubMed  CAS  Google Scholar 

  4. Van Nunen SA, O'Connor KS, Clarke LR, Boyle RX, Fernando SL. An association between tick bite reactions and red meat allergy in humans. Med J Aust. 2009;190:510–1.

    PubMed  Google Scholar 

  5. Jacquenet S, Moneret-Vautrin DA, Bihain BE. 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. 2009;124:603–5.

    Article  PubMed  CAS  Google Scholar 

  6. Jappe U. Update on meat allergy: α-Gal: a new epitope, a new entity? Hautarzt. 2012;63:299–306.

    Article  PubMed  CAS  Google Scholar 

  7. O'Neil BH, Allen R, Spigel DR, et al. High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol. 2007;25:3644–8.

    Article  PubMed  Google Scholar 

  8. Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med. 2008;358:1109–17.

    Article  PubMed  CAS  Google Scholar 

  9. Galili U, Rachmilewitz EA, Peleg A, Flechner I. A unique natural human IgG antibody with anti-alpha-galactosyl specificity. J Exp Med. 1984;160:1519–31.

    Article  PubMed  CAS  Google Scholar 

  10. •• Commins SP, James HR, Kelly LA, et al. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose. J Allergy Clin Immunol. 2011;127:1286–93.e1286. This study presents data related to tick bites inducing the IgE Ab response to alpha-gal. The report is the first example of a response to an ectoparasite giving rise to an important form of food allergy.

    Article  PubMed  CAS  Google Scholar 

  11. Commins SP, Platts-Mills TA. Anaphylaxis syndromes related to a new mammalian cross-reactive carbohydrate determinant. J Allergy Clin Immunol. 2009;124:652–7.

    Article  PubMed  CAS  Google Scholar 

  12. Childs JE, Paddock CD. The ascendancy of Amblyomma americanum as a vector of pathogens affecting humans in the United States. Annu Rev Entomol. 2003;48:307–37.

    Article  PubMed  CAS  Google Scholar 

  13. Nicholson WL, Allen KE, McQuiston JH, Breitschwerdt EB, Little SE. The increasing recognition of rickettsial pathogens in dogs and people. Trends Parasitol. 2010;26:205–12.

    Article  PubMed  Google Scholar 

  14. Salinas LJ, Greenfield RA, Little SE, Voskuhl GW. Tickborne infections in the southern United States. Am J Med Sci. 2010;340:194–201.

    Article  PubMed  Google Scholar 

  15. • Prevention CfDCa. Approximate distribution of the Lone Star Tick, 2011. Available at http://www.cdc.gov/ticks/maps/lone_star_tick.html. Edited by; accessed August 2012. Updated map that shows the expanding range of Lone Star Ticks in the US. The distribution of Lone Star Ticks now encompasses or includes 28 states.

  16. •• Morisset M, Richard C, Astier C, et al. Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose. Allergy. 2012;67:699–704. The authors previously identified three cases of delayed anaphylaxis to mammalian meat and reported on skin testing with cetuximab. More recently, they have extended their work to study other foods including goat, horse, and particularly pork and beef kidneys, as a cause of severe delayed reactions in patients with IgE Ab to alpha-gal.

    Article  PubMed  CAS  Google Scholar 

  17. Gronlund H, Adedoyin J, Commins SP, Platts-Mills TA, van Hage M. The carbohydrate galactose-alpha-1,3-galactose is a major IgE-binding epitope on cat IgA. J Allergy Clin Immunol. 2009;123:1189–91.

    Article  PubMed  Google Scholar 

  18. Pointreau Y, Commins SP, Calais G, Watier H, Platts-Mills TA. Fatal infusion reactions to cetuximab: role of immunoglobulin e-mediated anaphylaxis. J Clin Oncol. 2012;30:334. author reply 335.

    Article  PubMed  Google Scholar 

  19. Faveeuw C, Mallevaey T, Paschinger K, et al. Schistosome N-glycans containing core alpha 3-fucose and core beta 2-xylose epitopes are strong inducers of Th2 responses in mice. Eur J Immunol. 2003;33:1271–81.

    Article  PubMed  CAS  Google Scholar 

  20. Okano M, Satoskar AR, Nishizaki K, Abe M, Harn DA. Induction of Th2 responses and IgE is largely due to carbohydrates functioning as adjuvants on Schistosoma mansoni egg antigens. J Immunol. 1999;163:6712–7.

    PubMed  CAS  Google Scholar 

  21. Perzanowski MS, Ng'ang'a LW, Carter MC, et al. Atopy, asthma, and antibodies to Ascaris among rural and urban children in Kenya. J Pediatr. 2002;140:582–8.

    Article  PubMed  Google Scholar 

  22. Addo-Yobo EO, Woodcock A, Allotey A, et al. Exercise-induced bronchospasm and atopy in Ghana: two surveys ten years apart. PLoS Med. 2007;4:e70.

    Article  PubMed  Google Scholar 

  23. •• Arkestål K, Sibanda E, Thors C, et al. Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-α 1,3-galactose. J Allergy Clin Immunol. 2011;127:1024–8. The study highlights the issues that arise with IgE Ab to alpha-gal and the cross-reactivity pattern with mammalian epithelium and dander. Particular importance is noted in patients with a parasitic infection or where lifestyle decisions are in question (i.e. pet ownership).

    Article  PubMed  Google Scholar 

  24. Adedoyin J, Gronlund H, Oman H, Johansson SG, van Hage M. Cat IgA, representative of new carbohydrate cross-reactive allergens. J Allergy Clin Immunol. 2007;119:640–5.

    Article  PubMed  CAS  Google Scholar 

  25. Spiro RG, Bhoyroo VD. 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. 1984;259:9858–66.

    PubMed  CAS  Google Scholar 

  26. Crater SE, Peters EJ, Martin ML, Murphy AW, Platts-Mills TA. Expired nitric oxide and airway obstruction in asthma patients with an acute exacerbation. Am J Respir Crit Care Med. 1999;159:806–11.

    PubMed  CAS  Google Scholar 

  27. Peters E, Crater S, Phillips CD, Wheatley LM, Platts-Mills TA. Sinusitis and acute asthma in adults. Int Arch Allergy Immunol. 1999;118:372–4.

    Article  PubMed  CAS  Google Scholar 

  28. Ayuso R, Lehrer SB, Tanaka L, et al. IgE antibody response to vertebrate meat proteins including tropomyosin. Ann Allergy Asthma Immunol. 1999;83:399–405.

    Article  PubMed  CAS  Google Scholar 

  29. Jenkins JA, Breiteneder H, Mills EN. Evolutionary distance from human homologs reflects allergenicity of animal food proteins. J Allergy Clin Immunol. 2007;120:1399–405.

    Article  PubMed  CAS  Google Scholar 

  30. Spitzauer S. Allergy to mammalian proteins: at the borderline between foreign and self? Int Arch Allergy Immunol. 1999;120:259–69.

    Article  PubMed  CAS  Google Scholar 

  31. Restani P, Fiocchi A, Beretta B, et al. Meat allergy: III–Proteins involved and cross-reactivity between different animal species. J Am Coll Nutr. 1997;16:383–9.

    PubMed  CAS  Google Scholar 

  32. Drouet M, Sabbah A. The pork/cat syndrome or crossed reactivity between cat epithelia and pork meat. Monogr Allergy. 1996;32:164–73.

    PubMed  CAS  Google Scholar 

  33. Hilger C, Kohnen M, Grigioni F, Lehners C, Hentges F. Allergic cross-reactions between cat and pig serum albumin. Study at the protein and DNA levels. Allergy. 1997;52:179–87.

    Article  PubMed  CAS  Google Scholar 

  34. Drouet M, Sabbah A, Le Sellin J, et al. Fatal anaphylaxis after eating wild boar meat in a patient with pork-cat syndrome. Allerg Immunol (Paris). 2001;33:163–5.

    CAS  Google Scholar 

  35. Commins SP, Platts-Mills TA. Allergenicity of carbohydrates and their role in anaphylactic events. Curr Allergy Asthma Rep. 2010;10:29–33.

    Article  PubMed  CAS  Google Scholar 

  36. Galili U. The alpha-gal epitope and the anti-Gal antibody in xenotransplantation and in cancer immunotherapy. Immunol Cell Biol. 2005;83:674–86.

    Article  PubMed  CAS  Google Scholar 

  37. Wang Y, Ghoshal S, Ward M, et al. Chylomicrons promote intestinal absorption and systemic dissemination of dietary antigen (ovalbumin) in mice. PLoS One. 2009;4:e8442.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

These studies are primarily funded by National Institutes of Health grants AI-20565, U19-AI-070364, R21-AI-087985, and K08-AI-1085190.

Disclosure

Dr. Commins has served on the speakers’ bureau for Cornerstone Therapeutics and received compensation for speaking at the annual meeting for the Virginia Allergy Society.

Dr. Platts-Mills has served as a consultant for IBT Laboratories.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Allergy and Immunology, University of Virginia Health System, Charlottesville, VA, USA

    Thomas A. E. Platts-Mills

  2. Department of Internal Medicine & Pediatrics, Division of Allergy and Immunology, University of Virginia Health System, Charlottesville, VA, USA

    Scott P. Commins

  3. Division of Allergy, Asthma, and Immunology, University of Virginia Health System, P.O. Box 801355, Charlottesville, VA, 22908, USA

    Scott P. Commins & Thomas A. E. Platts-Mills

Authors
  1. Scott P. Commins
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas A. E. Platts-Mills
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Scott P. Commins.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Commins, S.P., Platts-Mills, T.A.E. Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal). Curr Allergy Asthma Rep 13, 72–77 (2013). https://doi.org/10.1007/s11882-012-0315-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-012-0315-y

Keywords

Search

Navigation