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Alpha-gal allergy

Abstract

Alpha-gal allergy, also known as meat allergy or Mammalian Meat Allergy (MMA), is a reaction to galactose-alpha-1,3-galactose (alpha-gal), whereby the body is overloaded with immunoglobulin E (IgE) antibodies on contact with the carbohydrate. The alpha-gal molecule is found in all mammals apart from Old World monkeys and the apes, which include humans. Anti-Gal is a human natural antibody which interacts specifically with the mammalian carbohydrate structure Gal alpha 1-3Gal beta 1-4GlcNAc-R, termed, the alpha-galactosyl epitope. Whereas anti-Gal is abundant in humans, apes and Old World monkeys, it is absent from New World monkeys, prosimians and nonprimate mammals.

Bites from certain ticks, such as the lone star tick in the US, which can transfer this carbohydrate to the victim have been implicated in the development of this delayed allergic response which is triggered by the consumption of mammalian meat products. Despite myths to the contrary, an alpha-gal allergy does not require the afflicted to become a vegetarian, as poultry and fish do not trigger a reaction.

The allergy most often occurs in the central and southern United States, which corresponds to the distribution of the lone star tick. In the Southern United States, where the tick is most prevalent, allergy rates are 32% higher than elsewhere. However, as doctors are not required to report the number of patients suffering the alpha-gal allergies, the true number of affected individuals is unknown. While there is no known cure, symptoms of the allergy may recede over time. Some patients report observing symptoms for over 20 years.

Signs and symptoms

A typical allergic reaction to alpha-gal has a delayed onset, occurring 3–8 hours after the consumption of mammalian meat products, instead of the typical rapid onset with most food allergies. After the delayed onset, the allergic response is typical of most food allergies, and especially an IgE mediated allergy, including severe whole-body itching, hives, angioedema, gastrointestinal upset, and possible anaphylaxis. In 70% of cases the reaction is accompanied by respiratory distress and as such is particularly harmful to those with asthma.

Alpha-gal allergies are the first food allergies to come with the possibility of delayed anaphylaxis. It is also the first food-related allergy to be associated with a carbohydrate, rather than a protein.

Cause

Alpha-gal allergies develop after a person has been bitten by the lone star tick in the United States, the European castor bean tick, and the paralysis tick in Australia. Alpha-gal is not naturally present in apes and humans, but is in all other mammals. If a tick feeds on another mammal, the alpha-gal will remain in its alimentary tract. The tick will then inject the alpha-gal into a person's skin, which in turn will cause the immune system to release a flood of IgE antibodies to fight off the foreign carbohydrate. Researchers still do not know which specific component of tick saliva causes the reaction.

A 2012 preliminary study found unexpectedly high rates of alpha-gal allergies in the Western and North Central parts of the United States, which suggests that the allergy may be spread by unknown tick species. Examples of alpha-gal allergies were even present in Hawaii, where none of the ticks identified with the allergies live. Human factors were suggested but no specific examples were provided.

Alpha-gal is present in the anti-cancer drug cetuximab, as well as the IV fluid replacements Gelofusine and Haemaccel. Blood thinners derived from porcine intestine and replacement heart valves derived from porcine tissue may also contain alpha-gal.

There has been at least one instance of a man with an alpha-gal allergy going into anaphylaxis after receiving a heart valve transplant. Some researchers have suggested that the alpha-gal which is prevalent in pig's tissue and used for xenografts may contribute to organ rejection.

Mechanism

The lone star tick injects alpha gal into the blood stream and then the immune system releases immunoglobulin E antibodies to fight this foreign sugar. After this reaction, the future intake of mammal meat with the same alpha gal will result in an allergy reaction. Symptoms of the allergy reaction are caused by too many IgE antibodies attacking the allergen, in this case the alpha-gal.

Diagnosis

A traditional skin prick allergy test for allergy to meat may give a false negative answer. Blood tests for IgE response indicating alpha-gal allergy have not been approved by the U.S. Food and Drug Administration (FDA), and must usually be purchased by private individuals, but are available and are in use. Determination of specific IgE to alpha-gal testing is commercially available. The highest sensitivity is observed with skin and basophil activation tests with cetuximab which is, however, limited by its high costs.

Prognosis

Unlike most food allergies, it may be possible for the alpha-gal allergy to recede with time, as long as the person is not bitten by another tick. The recovery period can take anywhere from eight months to five years. This recovery potential is not confirmed. More research needs to be conducted to determine why some patients seem to recover and some do not.

History

The allergy was first formally identified as originating from tick bites in 2002 by Thomas Platts-Mills. Platts-Mills and Scott Commins were attempting to discover why some people were reacting negatively to the carbohydrate in the cancer drug cetuximab. They had previously hypothesized that a fungal infection or parasite could lead to the allergy. It wasn't until Platts-Mills was bitten by a tick and developed alpha-gal allergies that his team also came to the conclusion that there was a link between tick bites and the allergy. They found that the IgE antibody response to the mammalian oligosaccharide epitope, alpha-gal, was associated with both the immediate-onset anaphylaxis during first exposure to intravenous cetuximab and the delayed-onset anaphylaxis 3 to 6 hours after ingestion of mammalian food products, such as beef or pork.

Alpha-gal allergies are very similar to pork–cat syndrome and hence misidentification can occur. Pork–cat syndrome usually elicits an immediate allergic response, while a true alpha-gal allergy typically features a delayed allergic reaction of 3 to 8 hours after ingestion of the allergen.