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 to check access.
These studies are primarily funded by National Institutes of Health grants AI-20565, U19-AI-070364, R21-AI-087985, and K08-AI-1085190.
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.
Papers of particular interest, published recently, have been highlighted as: •Of importance ••Of major importance
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.PubMedCrossRefGoogle Scholar
• 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.PubMedCrossRefGoogle Scholar
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.PubMedGoogle Scholar
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.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
•• 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.PubMedCrossRefGoogle Scholar
Commins SP, Platts-Mills TA. Anaphylaxis syndromes related to a new mammalian cross-reactive carbohydrate determinant. J Allergy Clin Immunol. 2009;124:652–7.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
Salinas LJ, Greenfield RA, Little SE, Voskuhl GW. Tickborne infections in the southern United States. Am J Med Sci. 2010;340:194–201.PubMedCrossRefGoogle Scholar
• 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.
•• 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.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
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.PubMedGoogle Scholar
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.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
•• 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).PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
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.PubMedGoogle Scholar
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.PubMedGoogle Scholar
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.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
Spitzauer S. Allergy to mammalian proteins: at the borderline between foreign and self? Int Arch Allergy Immunol. 1999;120:259–69.PubMedCrossRefGoogle Scholar
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.PubMedGoogle Scholar
Drouet M, Sabbah A. The pork/cat syndrome or crossed reactivity between cat epithelia and pork meat. Monogr Allergy. 1996;32:164–73.PubMedGoogle Scholar
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.PubMedCrossRefGoogle Scholar
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.Google Scholar
Commins SP, Platts-Mills TA. Allergenicity of carbohydrates and their role in anaphylactic events. Curr Allergy Asthma Rep. 2010;10:29–33.PubMedCrossRefGoogle Scholar
Galili U. The alpha-gal epitope and the anti-Gal antibody in xenotransplantation and in cancer immunotherapy. Immunol Cell Biol. 2005;83:674–86.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar