Clinical Information

Immunoglobulin E antibodies to galactose-alpha-1,3-galactose (alpha-gal), a carbohydrate commonly expressed on non-primate mammalian proteins, are capable of eliciting allergenic reactions.

Sensitization may occur through tick bites or exposure to the drug cetuximab. In the United States, individuals bitten by Amblyomma americanum, also known as the Lone Star tick, may develop IgE antibodies to alpha-gal, although sensitization to alpha-gal through other tick species has also been implicated.(1) The Lone Star tick was historically localized to the southern and southeastern United States but has now expanded its range into the central Midwest and northwards along the eastern seaboard. It is thought to be responsible for most cases of alpha-gal sensitization in the United States. The tick species that appears to be responsible for these responses in France is Ixodes ricinus, while in Australia it is Ixodes holocyclus.(2,3,4)

Signs and symptoms of an alpha-gal allergic reaction are often delayed compared with other food allergies. Upon exposure of sensitized subjects to non-primate mammalian meat (eg, beef, pork, venison) or meat-derived product such as gelatin, a delayed allergic response may ensue, often 3 to 6 hours after ingestion. Symptoms can include urticaria, angioedema, difficulty breathing, abdominal pain, vomiting, and even anaphylactic shock.

Individuals who have antibodies produced against alpha-gal following a tick bite or previous exposure to the drug cetuximab may experience anaphylaxis when given cetuximab. Cetuximab is a monoclonal antibody, which contains an alpha-gal epitope on the antigen binding fragment (Fab fragment) of the monoclonal drug. Unlike the delayed onset anaphylaxis associated with red meat consumption, individuals with IgE antibody response to alpha-gal can experience immediate onset anaphylaxis upon intravenous cetuximab administration.

Although most sensitizations to alpha-gal occur later in life, children who develop IgE antibodies to alpha-gal may also experience anaphylaxis and urticaria 3 to 6 hours after eating mammalian meat. Unlike their adult counterparts, who frequently present with anaphylaxis, the majority of children with this syndrome present with urticaria. Alpha-gal can also be found in mammalian milk, including cow and goat milk.

In vitro serum testing for IgE antibodies provides an indication of the immune response to allergens that may be associated with allergic disease.