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Alpha-gal syndrome

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Alpha-gal allergy
Other namesRed meat allergy
Mammalian Meat Allergy (MMA)
SpecialtyImmunology Edit this on Wikidata
SymptomsSymptoms
Durationunknown
Causesbites from certain species of ticks. (Predominantly the Lone Star tick.)
TreatmentDesensitization

Alpha-gal allergy — or mammalian meat allergy (MMA)[1] — is a type of red-meat allergy characterized by a delayed onset of symptoms (3-5 hours) after ingesting the provoking food and resulting from past exposure to tick bites. It was first reported in 2002.

Alpha-gal allergy 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] 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] The alpha-gal molecule is found in all mammals except apes, humans, and Old World monkeys.[3]

Bites from certain ticks, such as the lone star tick (Am. americanum) in the US, and the paralysis tick in Australia, 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] Individuals with alpha-gal allergy do not need to become strict vegetarians, because poultry, fish, and in rare cases for some people, lean meat such as venison does not trigger a reaction.[5]

Alpha-gal allergy has been reported in 17 countries on all 6 continents where humans are bitten by ticks, particularly the United States and Australia.[6] As of November 2019 Australia has the highest rate of mammalian meat allergy and tick anaphylaxis in the world.[7] In the US, the allergy most often occurs in the central and southern regions, which corresponds to the distribution of the lone star tick.[8] In the Southern United States, where the tick is most prevalent, allergy rates are 32% higher than elsewhere.[9] However, as doctors are not required to report the number of patients with alpha-gal allergy, the true number of affected individuals is unknown.[10] Alpha-gal has also been shown to exist in the saliva of Ix. scapularis but not Am. maculatum.[11]

Alpha-gal allergies are the first known food allergies that present the possibility of delayed anaphylaxis.[12][13][14] It is also the first known food-related allergy associated with a carbohydrate, rather than a protein.[13][15] Other mammalian products containing alpha-gal other than meat such as milk and gelatin may also trigger an allergic reaction.[16]

Symptoms

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.[17] In 70% of cases the reaction is accompanied by respiratory distress and as such is particularly harmful to those with asthma.[12]

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 and Ixodes (Endopalpiger) australiensis in Australia,[18][6] Haemaphysalis longicornis in Japan,[19] and a currently unknown tick in South Africa, possibly Amblyomma hebraeum.[20][21] 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][18] Researchers still do not know which specific component of tick saliva causes the reaction.[22]

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.[9] The study even found alpha-gal allergy cases in Hawaii, where no ticks identified with the allergies live.[22] Human factors were suggested, but no specific examples were provided.[9]

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.[18]

At least one instance of a man with an alpha-gal allergy going into anaphylaxis after receiving a heart valve transplant has been reported.[18] Some researchers have suggested that the alpha-gal in pig's tissue that surgeons use for xenografts might contribute to organ rejection.[23]

Mechanism

Recent research has shown that saliva from the lone star tick contains alpha-gal,[24] and that saliva is injected into the blood stream. The immune system then 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.[18][25]

Diagnosis

A traditional skin-prick allergy test for allergy to meat may give a false-negative answer.[14][26] Determination of specific IgE to alpha-gal testing is commercially available, as well as IgE testing to specific red meats.[27][17] Skin and basophil activation tests with cetuximab are the most sensitive, but high costs limit their use.[27]

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.[18][22][28]

Desensitization

So far, only two successful desensitizations have been performed on patients with an alpha-gal allergy.[29]

History

Ixodes holocyclus, the species of hard-bodied tick most likely to be responsible in Australia for instances of alpha-gal allergy.

The allergy was first formally identified as originating from tick bites in the United States in 2002 by Thomas Platts-Mills,[30] and independently by Sheryl van Nunen in Australia in 2007.[31][32][33]

Platts-Mills and Scott Commins were attempting to discover why some people were reacting negatively to the carbohydrate in the cancer drug cetuximab.[18][34] They had previously hypothesized that a fungal infection or parasite could lead to the allergy.[18][28] 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.[28] 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.[35]

Van Nunen, an immunologist specialising in allergies, had been practicing in a tick-prone area of Sydney, when 25 patients reported having allergic reactions to red meat after being bitten by ticks.[36][37] She later concluded that the relatively sudden rise in cases was the result of a local fox baiting program which began in 2003. Foxes were introduced to Australia and had decimated the local indigenous bandicoot population, hence the fox baiting program. However an unforeseen effect of the subsequent rise in the bandicoot population was the rise in ticks, as bandicoots are a major host for ticks, and thus the number of humans suffering tick bites.[38]

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.[39]

See also

References

  1. ^ Catalyst (ABC-TV program) first aired 8 November 2016
  2. ^ Commins SP, Platts-Mills TA (February 2013). "Delayed anaphylaxis to red meat in patients with IgE specific for galactose alpha-1,3-galactose (alpha-gal)". Current Allergy and Asthma Reports. 13 (1): 72–7. doi:10.1007/s11882-012-0315-y. PMC 3545071. PMID 23054628.
  3. ^ a b Galili U (1993). "Evolution and pathophysiology of the human natural anti-alpha-galactosyl IgG (anti-Gal) antibody". Springer Seminars in Immunopathology. 15 (2–3): 155–71. doi:10.1007/bf00201098. PMID 7504839.
  4. ^ "Alpha-Gal IgE Test - Galactose-alpha-1,3-galactose : Viracor-IBT Laboratories". Retrieved 9 January 2013.
  5. ^ a b c Williams L (December 27, 2013). "Just one bite". Sydney Morning Herald. Australia. p. 20.
  6. ^ a b Kwak M, Somerville C, van Nunen S (July 2018). "A novel Australian tick Ixodes (Endopalpiger) australiensis inducing mammalian meat allergy after tick bite". Asia Pacific Allergy. 8 (3): e31. doi:10.5415/apallergy.2018.8.e31. PMC 6073180. PMID 30079309.
  7. ^ Lawson, Kirsten (20 Nov 2019). "Gluten 'lifestylers' undermine efforts on coeliac disease". The Canberra Times. p. 4.
  8. ^ "Meat Allergy: Alpha-Gal Reaction From Lone-Star Ticks More Common In Central, Southern U.S. Regions". 2012-11-09. Retrieved 9 January 2013.
  9. ^ a b c Chan AL (November 9, 2012). "Where Meat Allergy From Ticks Is Most Common". Healthy Living.
  10. ^ Frazier A (March 20, 2014). "Tick bite makes Lusby woman allergic to meat". The Washington Post. pp. METRO, T20. Archived from the original on July 2, 2018.
  11. ^ Crispell, Gary; Commins, Scott P.; Archer-Hartman, Stephanie A.; Choudhary, Shailesh; Dharmarajan, Guha; Azadi, Parastoo; Karim, Shahid (2019). "Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy". Frontiers in Immunology. 10. doi:10.3389/fimmu.2019.01056. ISSN 1664-3224.
  12. ^ a b Wolver SE, Sun DR, Commins SP, Schwartz LB (February 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. {{cite journal}}: Unknown parameter |lay-date= ignored (help); Unknown parameter |lay-source= ignored (help); Unknown parameter |lay-url= ignored (help)
  13. ^ a b Alvarez A (July 25, 2012). "Tick bite leads to curious meat allergy". Milwaukee Journal Sentinel. Retrieved March 24, 2014.
  14. ^ a b "'Alpha-Gal' Syndrome". Cornell Cooperative Extension in Suffolk County. Cornell University.
  15. ^ Smith O (June 20, 2012). "Ticks causing mysterious meat allergy". CNN.
  16. ^ "Ingestion of mammalian meat and alpha-gal allergy: Clinical relevance in primary care". Retrieved 2020-07-02. Mammalian meat and milk (cow and goat) contain alpha-gal.
  17. ^ a b "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.
  18. ^ a b c d e f g h Zaraska M (December 3, 2013). "Want hives with that burger?". The Washington Post. pp. HEALTH, E01.
  19. ^ Cabezas-Cruz, Alejandro; Hodžić, Adnan; Román-Carrasco, Patricia; Mateos-Hernández, Lourdes; Duscher, Georg Gerhard; Sinha, Deepak Kumar; Hemmer, Wolfgang; Swoboda, Ines; Estrada-Peña, Agustín; de la Fuente, José (2019-05-31). "Environmental and Molecular Drivers of the α-Gal Syndrome". Frontiers in Immunology. 10: 1210. doi:10.3389/fimmu.2019.01210. ISSN 1664-3224. PMC 6554561. PMID 31214181.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  20. ^ Facey-Thomas H (2018-01-08). "Alpha-Gal". Allergy Foundation South Africa.
  21. ^ Mabelane (2018). "Predictive values of alpha-gal IgE levels and alpha-gal IgE:total IgE ratio and oral food challenge proven meat allergy in a population with a high prevalence of reported red meat allergy". Pediatric Allergy Immunology. 29 (8): 841–849. doi:10.1111/pai.12969. PMID 30144162.
  22. ^ a b c Kroen GC (November 16, 2012), Ticked Off About a Growing Allergy to Meat, ScienceNOW, retrieved March 24, 2014
  23. ^ Travis J (November 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.
  24. ^ Crispell, Gary; Commins, Scott P.; Archer-Hartman, Stephanie A.; Choudhary, Shailesh; Dharmarajan, Guha; Azadi, Parastoo; Karim, Shahid (17 May 2019). "Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy". Frontiers in Immunology. 10: 1056. doi:10.3389/fimmu.2019.01056. PMC 6533943. PMID 31156631.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  25. ^ "Hundreds on East End get meat allergy from Lone Star tick's bite". Newsday. Jul 30, 2017. Retrieved 2017-08-01.
  26. ^ Krishna N, 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.
  27. ^ a b Bircher AJ, Hofmeier KS, Link S, Heijnen I (February 2017). "Food allergy to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal): four case reports and a review". European Journal of Dermatology. 27 (1): 3–9. doi:10.1684/ejd.2016.2908. PMID 27873733.
  28. ^ a b c Goetz G (June 26, 2012). "Red Meat Allergy Likely Cause by Tick Bites". Food Safety News.
  29. ^ Unal D, Coskun R, Demir S, Gelincik A, Colakoglu B, Buyukozturk S (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. PMID 28132797.
  30. ^ "NIAID Scientists Link Cases of Unexplained Anaphylaxis to Red Meat Allergy". National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. U.S. Department of Health and Human Services. 28 November 2017.
  31. ^ Velasquez-Manoff, Moises (2018-07-24). "What the Mystery of the Tick-Borne Meat Allergy Could Reveal". The New York Times. ISSN 0362-4331. Retrieved 2019-03-08.
  32. ^ McKenna, Maryn (2018-12-11). "What is behind the spread of a mysterious allergy to meat?". The Guardian. ISSN 0261-3077. Retrieved 2019-03-08.
  33. ^ "Mammalian meat allergy: People on the northern beaches becoming allergic to red meat after tick bites". www.news.com.au. 2016-06-13. Retrieved 2019-03-08.
  34. ^ Commins SP, Platts-Mills TA (October 2009). "Anaphylaxis syndromes related to a new mammalian cross-reactive carbohydrate determinant". The Journal of Allergy and Clinical Immunology. 124 (4): 652–7. doi:10.1016/j.jaci.2009.08.026. PMC 2774206. PMID 19815111.
  35. ^ Berg EA, Platts-Mills TA, Commins SP (February 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.
  36. ^ McMahon, Alle (2019-01-18). "How tick bites can make some people allergic to meat and milk". ABC News. Retrieved 2019-03-08.
  37. ^ "Mammalian meat allergy: a tick-ing time bomb?". Australian Veterinary Association. Archived from the original on 2019-03-27. Retrieved 2019-03-08.
  38. ^ "MJA Podcasts 2018 Episode 27: Tick-induced allergies, with A/Prof Sheryl van Nunen". www.mja.com.au. Retrieved 2019-03-08.
  39. ^ Zaraska M (December 3, 2013). "Cat owners can also develop meat allergy". The Washington Post. pp. HEALTH, E05. Archived from the original on June 25, 2018.

Further reading

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