NIAID scientists link cases of unexplained anaphylaxis to red meat allergy

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, found that some patients’ seemingly inexplicable anaphylaxis was actually caused by an uncommon allergy to a molecule found naturally in red meat. They note that the allergy, which is linked to a history of a specific type of tick bite, may be difficult for patients and health care teams to identify.

An adult female Lone Star tick climbs on a plant. Bites from the juvenile form of this species are linked to the development of red meat allergy. Image credit: NIAID

Six of the 70 study participants evaluated for unexplained frequent anaphylaxis tested positive for an allergy to galactose-α-1,3-galactose, or alpha-gal, a sugar molecule found in beef, pork, lamb and other red meats.

The six adult male participants all had IgE antibodies — immune proteins associated with allergy — to alpha-gal in their blood. After implementing diets free of red meat, none of them experienced anaphylaxis in the 18 months to 3 years during which they were followed.

While the prevalence of allergy to alpha-gal, or “alpha-gal syndrome” is not known, researchers have observed that it occurs mostly in people living in the Southeast region of the United States and certain areas of New York, New Jersey and New England.

This distribution may occur because most people with an allergy to alpha-gal, including all six participants evaluated at NIH, have a history of bites from juvenile Ambylomma americanum, or Lone Star ticks.

The study authors say physicians may have mistakenly diagnosed these patients as having unexplained anaphylaxis because alpha-gal allergy presents differently from more common food allergies and routine allergy tests do not typically scan for antibodies to alpha-gal.

Furthermore, most allergic reactions to common food allergens, such as peanuts or crustacean shellfish, begin about 5 to 30 minutes after a person is exposed.

For unknown reasons, allergic reactions to alpha-gal may occur between 3 to 6 hours after red meat consumption, making it difficult to identify what substance caused the reaction. Some episodes may even begin overnight when a person is sleeping, which is a particularly uncommon presentation for anaphylaxis.

Among the study participants with alpha-gal allergy evaluated at NIH, two also had a rare condition called indolent systemic mastocytosis, or ISM.

People with ISM have an abnormally elevated number of mast cells, an immune cell type which contributes to anaphylaxis and other allergic symptoms by releasing histamine and other chemicals that cause inflammation.

The participants with ISM experienced more severe reactions than those without ISM, even though they had lower levels of antibodies to alpha-gal. This finding builds on evidence that mast cell abnormalities may increase the likelihood of people developing allergies and experiencing severe reactions, including allergies and reactions to alpha-gal. (National Institutes of Health)

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