Alpha-gal allergy

Alpha-gal allergy
Synonyms meat allergy
Mammalian Meat Allergy (MMA)
Symptoms Symptoms
Duration unknown
Causes repeated bites from certain species of ticks
Treatment Desensitization

Alpha-gal allergy, also known as meat allergy or mammalian meat allergy (MMA),[1] 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.[2] 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 that interacts specifically with the mammalian carbohydrate structure gal alpha 1-3Gal beta 1-4GlcNAc-R, termed, the alpha-galactosyl epitope.[3] Whereas alpha-gal is absent from humans, apes, and Old World monkeys, it is abundant in New World monkeys, prosimians, and nonprimate mammals.[3]

Bites from certain ticks, such as the lone star tick in the US, which can transfer this carbohydrate to a victim, have been implicated in the development of this delayed allergic response to consumption of mammalian meat products.[4] Despite myths to the contrary, individuals with alpha-gal allergy do not need to become vegetarians, because poultry, fish, and in some people, lean meat such as venison do not trigger a reaction.[5]

The allergy most often occurs in the central and southern United States, which corresponds to the distribution of the lone star tick.[6] In the Southern United States, where the tick is most prevalent, allergy rates are 32% higher than elsewhere.[7] However, as doctors are not required to report the number of patients with alpha-gal allergy, the true number of affected individuals is unknown.[8] While no cure is known, symptoms of the allergy may recede over time.[9]

A typical allergic reaction to alpha-gal has a delayed onset, occurring 3–8 hours after the consumption of mammalian meat products, in contrast to the typical rapid onset of most food allergies. After the delayed onset, the allergic response is like most food allergies, and especially an IgE-mediated allergy, including severe whole-body itching, hives, angioedema, gastrointestinal upset, and possible anaphylaxis.[10] In 70% of cases the reaction is accompanied by respiratory distress and as such is particularly harmful to those with asthma.[11]

Alpha-gal allergies are the first known food allergies that present the possibility of delayed anaphylaxis.[11][12][13] It is also the first known food-related allergy associated with a carbohydrate, rather than a protein.[12][14]

Cause

Amblyomma americanum, a vector for the allergy

Alpha-gal allergies develop after a person has been bitten by the lone star tick in the United States, the European castor bean tick, the paralysis tick in Australia[15] and a currently unknown tick in South Africa[16]. Alpha-gal is not naturally present in apes, Old World monkeys, or humans, but is in all other mammals. If a tick feeds on another mammal, the alpha-gal remains in its alimentary tract.[5] The tick then injects the alpha-gal into a person's skin, which causes the immune system to release a flood of IgE antibodies to fight the foreign carbohydrate.[5][15] Researchers still do not know which specific component of tick saliva causes the reaction.[17]

A 2012 preliminary study found unexpectedly high rates of alpha-gal allergy in the Western and North Central parts of the United States. This suggests that unknown tick species may spread the allergy.[7] The study even found alpha-gal allergy cases in Hawaii, where no ticks identified with the allergies live.[17] Human factors were suggested, but no specific examples were provided.[7]

Alpha-gal is present in the anticancer drug cetuximab, as well as the intravenous fluid replacements Gelofusine and Haemaccel. Blood thinners derived from porcine intestine and replacement heart valves derived from porcine tissue may also contain alpha-gal.[15]

At least one instance of a man with an alpha-gal allergy going into anaphylaxis after receiving a heart valve transplant has been reported.[15] Some researchers have suggested that the alpha-gal in pig's tissue that surgeons use for xenografts might contribute to organ rejection.[18]

Mechanism

The lone star tick injects alpha-gal into the blood stream, and then the immune system releases IgE antibodies to fight this foreign sugar. After this reaction, the future intake of mammal meat with the same alpha-gal causes an allergic reaction. Symptoms of the allergy reaction are caused by too many IgE antibodies attacking the allergen, in this case the alpha-gal.[15][9]

Diagnosis

A traditional skin-prick allergy test for allergy to meat may give a false-negative answer.[13][19] Blood tests for IgE response indicating alpha-gal allergy have not been approved by the U.S. Food and Drug Administration, and must usually be purchased by private individuals, but are available and in use.[8] Determination of specific IgE to alpha-gal testing is commercially available.[20][10] Skin and basophil activation tests with cetuximab are the most sensitive, but high costs limit their use.[20]

Prognosis

Unlike most food allergies, in some people, the alpha-gal allergy may recede over time, as long as the person is not bitten by another tick. The recovery period can take 8 months to 5 years.[15][17][21]

Desensitization

So far, only two successful desensitizations have been performed on patients with an alpha-gal allergy[22]

History

The allergy was first formally identified as originating from tick bites in 2002 by Thomas Platts-Mills.[23] Platts-Mills and Scott Commins were attempting to discover why some people were reacting negatively to the carbohydrate in the cancer drug cetuximab.[15][24] They had previously hypothesized that a fungal infection or parasite could lead to the allergy.[15][21] When Platts-Mills was bitten by a tick and developed alpha-gal allergies, his team came to the conclusion that a link existed between tick bites and the allergy.[21] 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.[25]

Alpha-gal allergies are similar to pork–cat syndrome, 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.[26]

References

  1. ↑ Catalyst (ABC-TV program) first aired 8 November 2016
  2. ↑ Commins, SP; Platts-Mills, TA (2013). "Delayed anaphylaxis to red meat in patients with IgE specific for galactose alpha-1,3-galactose (alpha-gal)". Curr Allergy Asthma Rep. 13 (1): 72–7. doi:10.1007/s11882-012-0315-y. PMC 3545071. PMID 23054628.
  3. 1 2 Galili, U. (1993). "Evolution and pathophysiology of the human natural anti-alpha-galactosyl IgG (anti-Gal) antibody". Springer Seminars in Immunopathology. 15 (2–3): 155–171. doi:10.1007/bf00201098. ISSN 0344-4325. PMID 7504839.
  4. ↑ "Alpha-Gal IgE Test - Galactose-alpha-1,3-galactose : Viracor-IBT Laboratories". Retrieved 9 January 2013.
  5. 1 2 3 Williams, Louise (December 27, 2013). "Just one bite". Sydney Morning Herald. Australia. p. 20.
  6. ↑ "Meat Allergy: Alpha-Gal Reaction From Lone-Star Ticks More Common In Central, Southern U.S. Regions". Retrieved 9 January 2013.
  7. 1 2 3 Chan, Amanda L. (November 9, 2012). "Where Meat Allergy From Ticks Is Most Common". Healthy Living.
  8. 1 2 Frazier, Andrea (March 20, 2014). "Tick bite makes Lusby woman allergic to meat". The Washington Post. pp. METRO, T20.
  9. 1 2 "Hundreds on East End get meat allergy from Lone Star tick's bite". Newsday. Jul 30, 2017. Retrieved 2017-08-01.
  10. 1 2 "Viracor-IBT Laboratories Launches the First Assay to Identify a New Type of Delayed, IgE-based Allergic Reaction to Certain Meats" (Press release). Viracor-IBT Laboratories. September 13, 2010. Retrieved October 17, 2016.
  11. 1 2 Wolver, Susan E.; Sun, Diane R.; Commins, Scott P.; Schwartz, Lawrence B. (2013). "A peculiar cause of anaphylaxis: no more steak? The journey to discovery of a newly recognized allergy to galactose-alpha-1,3-galactose found in mammalian meat". Journal of General Internal Medicine. 28 (2): 322–5. doi:10.1007/s11606-012-2144-z. PMC 3614139. PMID 22815061. Lay summary – ScienceDaily (July 24, 2012).
  12. 1 2 Alvarez, Amanda (July 25, 2012). "Tick bite leads to curious meat allergy". Milwaukee Journal Sentinel. Retrieved March 24, 2014.
  13. 1 2 "'Alpha-Gal' Syndrome".
  14. ↑ Smith, Olivia (June 20, 2012). "Ticks causing mysterious meat allergy". CNN.
  15. 1 2 3 4 5 6 7 8 Zaraska, Marta (December 3, 2013). "Want hives with that burger?". The Washington Post. pp. HEALTH, E01.
  16. ↑ http://www.allergyfoundation.co.za/alpha-gal/
  17. 1 2 3 Kroen, Gretchen Cuda (November 16, 2012), Ticked Off About a Growing Allergy to Meat, ScienceNOW, retrieved March 24, 2014
  18. ↑ Travis, John (1995). "The xeno-solution: perils and promise of transplanting animal organs into people". Science News. 148 (19): 298–301. doi:10.2307/4018063. JSTOR 4018063. PMID 11653203.
  19. ↑ Krishna, Neal; Krishna, S.; Krishna, R. (November 2017). "P112 Correlation between clinical findings and laboratory tests for alpha gal sensitivity". Annals of Allergy, Asthma & Immunology. 119 (5): S37. doi:10.1016/j.anai.2017.08.136. ISSN 1081-1206.
  20. 1 2 Bircher, Andreas J.; Hofmeier, Kathrin Scherer; Link, Susanne; Heijnen, Ingmar (2017-01-01). "Food allergy to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal): four case reports and a review". European Journal of Dermatology. 27 (1). doi:10.1684/ejd.2016.2908. ISSN 1167-1122.
  21. 1 2 3 Goetz, Gretchen (June 26, 2012). "Red Meat Allergy Likely Cause by Tick Bites". Food Safety News.
  22. ↑ Unal, Derya; Coskun, Raif; Demir, Semra; Gelincik, Asli; Colakoglu, Bahauddin; Buyukozturk, Suna (2017). "Successful beef desensitization in 2 adult patients with a delayed-type reaction to red meat". The Journal of Allergy and Clinical Immunology: In Practice. 5 (2): 502–503. doi:10.1016/j.jaip.2016.12.008. ISSN 2213-2198.
  23. ↑ https://www.niaid.nih.gov/news-events/niaid-scientists-link-cases-unexplained-anaphylaxis-red-meat-allergy
  24. ↑ Commins, Scott P.; Platts-Mills, Thomas A. E. (Oct 2009). "Anaphylaxis syndromes related to a new mammalian cross-reactive carbohydrate determinant". The Journal of Allergy and Clinical Immunology. 124 (4): 652–657. doi:10.1016/j.jaci.2009.08.026. ISSN 0091-6749. PMC 2774206. PMID 19815111.
  25. ↑ Berg, Emily A.; Platts-Mills, Thomas A.E.; Commins, Scott P. (2014). "Drug allergens and food—the cetuximab and galactose-α-1,3-galactose story". Annals of Allergy, Asthma & Immunology. 112 (2): 97–101. doi:10.1016/j.anai.2013.11.014. PMC 3964477. PMID 24468247.
  26. ↑ Zaraska, Marta (December 3, 2013). "Cat owners can also develop meat allergy". The Washington Post. pp. HEALTH, E05.
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