Chapter 7 - Anti-Gal IgE Mediates Allergies to Red Meat

Abstract

Immunoglobulin class (isotype) switch to anti-Gal IgE was first observed in cancer patients receiving an immunotherapy treatment by infusion of the monoclonal antibody cetuximab (anti-epidermal growth factor receptor antibody). When produced in a hybridoma, this antibody carries the α-gal epitope, which binds anti-Gal IgE antibody in these patients, inducing allergic and anaphylactic reactions. Studies on the production of anti-Gal IgE indicated that it is rare in Northern regions of the United States (<1%) but is frequently found Southern regions (>20%). The production of anti-Gal IgE was further found to correlate with allergies to red meat (beef, pork, and lamb). One of the reasons for class switch from anti-Gal IgM or IgG1 to IgE was found to be “lone star” (Amblyomm americanum) tick bites. Bites of the ticks Ixodes ricinus in Europe, Haemaphysalis longicornis in Asia and Ixodes holocyclus in Australia were found to cause similar seroconversion to anti-Gal IgE and appearance of allergic reactions to red meat. Such allergies also are found with pork kidneys because they contain very large amounts of α-gal epitopes. The substances in tick saliva which stimulate the class switch in anti-Gal B cells into IgE producing cells have not been identified yet. Prevention of allergic reactions to α-gal epitopes may be achieved by identifying patients producing anti-Gal IgE, either by the use of a lab test or by a skin test with natural or synthetic α-gal epitopes linked to lipids or to other molecules. Use of therapeutic natural or recombinant glycoproteins and monoclonal antibodies lacking α-gal epitopes will also prevent anti-Gal IgE-mediated allergic reactions. This may be achieved by enzymatic destruction of α-gal epitopes with recombinant α-galactosidase or by using eukaryotic expression systems confirmed not to include the biosynthetic pathway for synthesis of α-gal epitopes. Because such biosynthetic pathways are also present in mammary glands of nonprimate mammals, recombinant therapeutic glycoproteins produced in mammary glands and secreted in milk of transgenic farm animals should be evaluated for presence of α-gal epitopes. If present, the α-gal epitopes may be destroyed enzymatically with α-galactosidase. Alternatively, the milk may be produced in knockout mammals for the α1,3GT gene, i.e., mammals that lack the ability to synthesize the α-gal epitope. Lastly, it would be of interest to determine whether red meat from cows, pigs, or lambs engineered to lack α-gal epitopes by disruption of the α1,3GT (GGTA1) gene, can be consumed by individuals producing anti-Gal IgE without having allergic reactions to this food.