Alpha-gal syndrome
Alpha-gal syndrome | |
---|---|
Other names | Alpha-gal syndrome (AGS) Acquired red meat allergy Mammalian meat allergy (MMA) |
Specialty | Allergy, immunology |
Symptoms | Abdominal pain, anaphylaxis, angiodema, headaches, congestion, diarrhea, faintness, hives, nausea, rhinorrhea often with sternutation |
Usual onset | Delayed |
Duration | Unknown |
Causes | Bites from certain species of ticks |
Diagnostic method | Clinical diagnosis, blood tests |
Prevention | Avoidance of tick bites |
Treatment | Anti-histamines, epinephrine, desensitization |
Alpha-gal syndrome (AGS), also known as alpha-gal allergy or mammalian meat allergy (MMA),[1] is a type of acquired allergy characterized by a delayed onset of symptoms (3–8 hours) after ingesting mammalian meat. The condition results from past exposure to certain tick bites. It was first reported in 2002. Symptoms of the allergy vary greatly between individuals and include rash, hives, nausea or vomiting, difficulty breathing, drop in blood pressure, dizziness or faintness, diarrhea, severe stomach pain, and possible anaphylaxis.[2][3]
Alpha-gal allergy is a reaction to the carbohydrate galactose-alpha-1,3-galactose ("alpha-gal"), whereby the body is overloaded with immunoglobulin E (IgE) antibodies on exposure to the carbohydrate.[4] Anti-gal is a human natural antibody that interacts specifically with the mammalian carbohydrate structure gal alpha 1-3Gal beta 1-4GlcNAc-R (the alpha-galactosyl epitope).[5] The alpha-gal molecule is found in all mammals except catarrhines (apes and Old World monkeys),[5] the taxonomic branch that includes humans.
In 2006, researchers Thomas Platts-Mills and Scott Commins attempted to discover why some people were allergic to the cancer drug cetuximab.[6][7][8] They discovered that these individuals had IgE antibodies in their blood that were specifically targeted to the portion of cetuximab which contained the alpha-gal carbohydrate.[8] 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.[9] 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.
Bites from specific tick species, such as the Lone Star tick (Amblyomma americanum) in the US, and the paralysis tick (Ixodes holocyclus) 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 ("red meat").[2] Healthcare providers recommend avoiding food products containing beef, pork, lamb, venison, rabbit, and offal to avoid triggering an allergic reaction.[2][10] Some afflicted individuals are so hypersensitive to alpha-gal that the allergy can cross-react with mammalian gelatin and even some dairy products.[2][10] Individuals with an alpha-gal allergy do not need to become strict vegetarians because reptile meats, poultry - including red meat from ostriches, emus, and other ratites, and seafood naturally do not contain alpha-gal.[2] Increasing evidence now suggests reactions to certain substances with traces of alpha-gal used in the preparation of certain medications, including nonsteroidal anti-inflammatory drugs (NSAIDs) and other analgesics and pain medications.[3]
Alpha-gal allergy has been reported in 17 countries on all six continents where humans are bitten by ticks, particularly the United States and Australia.[11] Alpha-gal allergies are the first known food allergies that present the possibility of delayed anaphylaxis.[12][13][14] They are also the first known food-related allergies associated with a carbohydrate, rather than a protein.[13][15]
Symptoms
[edit]A typical allergic reaction to alpha-gal has a delayed onset, occurring 3–8 hours after consuming mammalian meat products. However, there have been some instances of onset of symptoms occurring within 2 hours.[8] 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.[2][16] Anaphylactic reactions are seen in approximately 60% of afflicted individuals.[3]
![](https://upload.wikimedia.org/wikipedia/commons/thumb/8/8f/Signs_and_symptoms_of_anaphylaxis.svg/220px-Signs_and_symptoms_of_anaphylaxis.svg.png)
There have been cases where gastrointestinal symptoms arise without pruritus, hives, or other skin involvement. This presentation is not typical of food allergies, which can make initial suspicion of alpha-gal syndrome less likely.[8] In 70% of cases, the reaction is accompanied by respiratory distress and is particularly harmful to those with asthma.[12] However, not every exposure to alpha-gal results in allergic reaction for some people with the allergy.[2]
It is worth noting that symptoms and overall reactions can vary greatly between individuals with alpha-gal syndrome.[3] It has been found that other factors, including exercise and alcohol consumption, can potentially affect an individual's symptoms and overall reactivity to alpha-gal.[3] Increased risk has also been discovered in those without type B or type AB blood, as the type B blood antigen is similar to alpha-gal and may confer some level of immunity.[3]
The severity of symptoms and overall reaction to alpha-gal have been found to correlate with the amount of alpha-gal carbohydrate in the ingested food or drug.[8]
Cause and mechanism
[edit]![](https://upload.wikimedia.org/wikipedia/commons/thumb/2/29/Amblyomma_americanum_tick.jpg/220px-Amblyomma_americanum_tick.jpg)
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 or Ixodes (Endopalpiger) australiensis in Australia,[6][11] Haemaphysalis longicornis in Japan,[17] or a currently unknown tick in South Africa, possibly Amblyomma hebraeum.[18][19] Alpha-gal is not naturally present in apes, Old World monkeys, or humans, but is in all other mammals.[16] If a tick feeds on another mammal, the alpha-gal remains in its alimentary tract.
The tick injects the alpha-gal into a person's skin with its bite. Recent research has shown that saliva from the lone star tick contains alpha-gal,[20] and that saliva is injected into the bloodstream. Researchers still do not know which specific component of tick saliva causes the reaction.[21] The immune system then releases a flood of IgE antibodies to fight this foreign sugar.[2] After this reaction, the future intake of mammalian meat with the same alpha-gal causes an allergic reaction.[2] Symptoms of the allergy reaction are caused by too many IgE antibodies attacking the allergen – the alpha-gal.[2][6] Other types of ticks are suspected of causing similar problems.[22] Only a small percentage of children and adults will acquire a red meat allergy after receiving a bite from a lone star tick.[23]
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.[24] The study found alpha-gal allergy cases in Hawaii, where no ticks identified with the allergies live.[21] Human factors were suggested, but no specific examples were provided.[24]
Blood thinners derived from porcine intestine and replacement heart valves derived from porcine tissue may also contain alpha-gal.[6] Alpha gal is found on the fragment-antigen binding (Fab) fragment of the recombinant monoclonal cetuximab antibody used in the immunotherapy treatment of metastatic colon cancer. Immediate hypersensitivities and reactions, specifically concentrated in the southern part of the United States, can be seen from the alpha-gal components of this anti-cancer drug.[25][26][2] Increasing evidence now suggests reactions to certain substances with traces of alpha-gal used in the preparation of certain medications, including nonsteroidal anti-inflammatory drugs (NSAIDs) and other analgesics and pain medications.[3]
Anaphylactic transfusion reactions have been reported in patients with presumed alpha-gal syndrome who had type O blood and received group B plasma or platelets.[27] The B blood group antigen is antigenically similar to Galactose-alpha-1,3-Galactose.[28]
Diagnosis
[edit]Diagnosis begins with initial suspicion of alpha-gal syndrome following a thorough review of an individual's medical history and clinical symptoms.[3] Regarding laboratory testing, diagnosis tends to be difficult, and no specific test is recommended over others.[3]
A blood test for the specific antigen, IgE, to the alpha-gal carbohydrate, is commonly used for diagnosis in clinical practice. Typically, a level of 1% for IgE specific for alpha-gal out of total IgE in the body has been identified in patients with alpha-gal syndrome.[8] Traditional skin-prick allergy tests for allergy to meat may give a false-negative answer and are not generally considered reliable.[29][8] Skin and basophil activation tests with cetuximab are the most sensitive, but high costs limit their use.[30]
In certain instances in which a person does not present with the typical symptoms and history of alpha-gal syndrome but is found to have elevated alpha-gal IgE levels, improvement with avoidance of red meat can be diagnostic, as well.[8]
Prognosis
[edit]There is no cure for alpha-gal; the main form of management is abstaining from mammalian meat, including lamb, beef, pork, and other mammalian products if necessary.[10][8] These products have been found to have the highest risk of reaction, whereas dairy products present a much lower risk. Avoidance of dairy is not generally recommended as most afflicted individuals do not have reactions to dairy consumption.[8]
Unlike most food allergies, in some people, the alpha-gal allergy may recede over time as long as another tick does not bite the person. It has been found that with avoidance of further tick bites, levels of serum IgE decline.[8] The recovery period can take 8 months to 5 years.[6][21][9]
Treatment
[edit]In addition to avoiding triggers, such as mammalian meat, treatment is aimed at alleviating symptoms and is highly dependent on severity. If an allergic individual who only experiences relatively mild symptoms consumes food containing alpha-gal, then treatment with over-the-counter antihistamines may be acceptable.[23] In cases where more severe reactions—like anaphylaxis—are observed, admission to a hospital for emergency treatment is necessary.[8] In these situations, treatment is the same as for any anaphylactic reaction, and necessitates epinephrine administration. [31]
Desensitization
[edit]As of 2017, only two successful desensitizations have been performed on patients with an alpha-gal allergy.[32]
Prevention and tick removal
[edit]Tick bites can be prevented by treating clothing and gear with products containing 0.5% permethrin and avoiding areas inhabited by ticks.[33] Other recommendations are to conduct tick checks after coming inside, remove outdoor clothing articles and run them in a dryer on high heat to kill undetected ticks. Taking a shower or bath promptly can aid in detecting ticks on the skin.[34]
Debate exists around the best method of tick removal. Low-quality evidence favors mechanical techniques over chemical treatments such as gasoline, petroleum jelly, or clear fingernail polish. Mechanical techniques involve pulling with forceps or commercial devices. Pulling is slightly favored over rotation with forceps to remove ticks.[35]
History
[edit]![](https://upload.wikimedia.org/wikipedia/commons/thumb/e/e1/Bush_Ticks_found_on_a_Spotted-tailed_quoll_%283%29.jpg/220px-Bush_Ticks_found_on_a_Spotted-tailed_quoll_%283%29.jpg)
The allergy was first formally identified as originating from tick bites in the United States in 2002 by Thomas Platts-Mills,[36] and independently by Sheryl van Nunen in Australia in 2007.[37][38][39]
Platts-Mills, Tina Hatley Merritt, and Scott Commins were attempting to discover why some people were reacting negatively to the cancer drug cetuximab.[6][7][8] They had previously hypothesized that a fungal infection or parasite could lead to the allergy.[6][9] They discovered that these individuals had IgE antibodies in their blood that were specifically targeted to the portion of cetuximab which contained the alpha-gal carbohydrate.[8] When Platts-Mills was bitten by a tick and developed alpha-gal allergies, his team concluded that a link existed between tick bites and the allergy.[9] 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.[40]
As of November 2019, Australia has the highest rate of mammalian meat allergy and tick anaphylaxis worldwide.[41] In the US, the allergy most often occurs in the central and southern regions, which corresponds to the distribution of the Lone Star tick.[42] In the Southern United States, where the tick is most prevalent, allergy rates are 32% higher than elsewhere.[24] However, as physicians are not required to report the number of patients with alpha-gal allergy, the true number of affected individuals is unknown. Arkansas was the first state to make alpha-gal syndrome a reportable condition in the United States. [43] Alpha-gal has also been shown to exist in the saliva of Ixodes scapularis but not Amblyomma maculatum.[20]
In 2021, University of Tennessee entomologist Becky Trout Fryxell reported that more cases of Alpha-Gal syndrome are occurring from those who encounter the Lone Star tick: "[The tick] likes to feed on dogs, deer, and seems to always find people as well," said Fryxell. "It has the ability to transmit a lot of pathogens too. And it's also associated with a tick meat allergy, which unfortunately is becoming pretty common."[44]
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.[45][46] She later concluded that the relatively sudden rise in cases was the result of a local fox baiting program that 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, thus the number of humans suffering tick bites.[47]
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.[48]
In 2020, the U.S. Food and Drug Administration approved the genetic modification of pigs so they do not produce alpha-gal sugars. Pigs developed with the trademarked name GalSafe may be able to be eaten safely by people with alpha-gal allergy.[49] They may also produce alpha-gal-safe drugs,[50] and their organs can also be used for xenotransplantation.[51]
For those undergoing surgery, possible triggering agents include porcine-derived heart valves, insulin, heparin, thrombin, and surgifoam powder.[52]
New American guidelines published in 2023 recommended physicians to suspect alpha-gal syndrome in cases with abdominal pain and GI symptoms, but without traditional allergy symptoms like hives.[22]
See also
[edit]References
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- ^ a b c d e f g h i Vaz-Rodrigues, Rita; Mazuecos, Lorena; de la Fuente, José (July 2022). "Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS)". Journal of Asthma and Allergy. 15: 957–970. doi:10.2147/JAA.S265660. ISSN 1178-6965. PMC 9307871. PMID 35879928.
- ^ 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.
- ^ 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. S2CID 33149564.
- ^ a b c d e f g Zaraska, Marta (December 3, 2013). "Want hives with that burger?". The Washington Post. pp. HEALTH, E01.
- ^ a b 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.
- ^ a b c d e f g h i j k l m n Platts-Mills, Thomas A.E.; Li, Rung-chi; Keshavarz, Behnam; Smith, Anna R.; Wilson, Jeffrey M. (January 2020). "Diagnosis and Management of Patients with the α-Gal Syndrome". The Journal of Allergy and Clinical Immunology: In Practice. 8 (1): 15–23.e1. doi:10.1016/j.jaip.2019.09.017. ISSN 2213-2198. PMC 6980324. PMID 31568928.
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- ^ 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.
- ^ 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.
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- ^ a b Mabelane, T.; Ogunbanjo, G. A. (2019). "Ingestion of mammalian meat and alpha-gal allergy: Clinical relevance in primary care". African Journal of Primary Health Care & Family Medicine. 11 (1): e1–e5. doi:10.4102/phcfm.v11i1.1901. PMC 6494999. PMID 31038347.
Mammalian meat and milk (cow and goat) contain alpha-gal.
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- ^ a b 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.
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- ^ Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M (2008). "Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose". New England Journal of Medicine. 358 (11): 1109–17. doi:10.1056/NEJMoa074943. PMC 2361129. PMID 18337601.
- ^ Dunkman WJ, Rycek W, Manning MW (2019). "What Does a Red Meat Allergy Have to Do With Anesthesia? Perioperative Management of Alpha-Gal Syndrome". Anesthesia and Analgesia. 129 (5): 1242–1248. doi:10.1213/ANE.0000000000003460. PMID 29847378.
- ^ Miller MJ, Lee P, Lee BG, Flegel WA, West-Mitchell K, Conry-Cantilena K, De Giorgi V. Consideration for alpha-gal syndrome in two critically ill persons with group O blood who received group B plasma. Transfusion. 2024 May;64(5):949-951. doi: 10.1111/trf.17811. Epub 2024 Apr 3. PMID: 38566573; PMCID: PMC11104486.
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- ^ 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.
- ^ 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. S2CID 2400078.
- ^ Commins, Scott P. (2020-07-02). "Diagnosis & management of alpha-gal syndrome: lessons from 2,500 patients". Expert Review of Clinical Immunology. 16 (7): 667–677. doi:10.1080/1744666X.2020.1782745. ISSN 1744-666X. PMC 8344025. PMID 32571129.
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- ^ CDC (2020-07-01). "Preventing tick bites on people | CDC". Centers for Disease Control and Prevention. Retrieved 2021-07-22.
- ^ Eisen L. Personal protection measures to prevent tick bites in the United States: Knowledge gaps, challenges, and opportunities. Ticks Tick Borne Dis. 2022 Jul;13(4):101944. doi: 10.1016/j.ttbdis.2022.101944. Epub 2022 Mar 26. PMID: 35364518; PMCID: PMC10859966.
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- ^ "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.
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- ^ McKenna, Maryn (2018-12-11). "What is behind the spread of a mysterious allergy to meat?". The Guardian. Retrieved 2019-03-08.
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- ^ 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.
- ^ Lawson, Kirsten (20 Nov 2019). "Gluten 'lifestylers' undermine efforts on coeliac disease". The Canberra Times. p. 4.
- ^ "Meat Allergy: Alpha-Gal Reaction From Lone-Star Ticks More Common In Central, Southern U.S. Regions". HuffPost. 2012-11-09. Retrieved 9 January 2013.
- ^ Frazier, Andrea (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.
- ^ Lunsford, Erica (July 12, 2021). "Entomologist warns about tickborne meat allergy". WVLT TV News, Knoxville TN. Archived from the original on 2021-07-21. Retrieved 2021-07-21.
- ^ McMahon, Alle (2019-01-18). "How tick bites can make some people allergic to meat and milk". ABC News. Retrieved 2019-03-08.
- ^ "Mammalian meat allergy: a tick-ing time bomb?". Australian Veterinary Association. Archived from the original on 2019-03-27. Retrieved 2019-03-08.
- ^ "Tick-induced allergies, with Associate Professor Sheryl van Nunen". MJA Podcasts. Medical Journal of Australia. 2018. Episode 27. Retrieved 2019-03-08.
- ^ Zaraska, Marta (December 3, 2013). "Cat owners can also develop meat allergy". The Washington Post. pp. HEALTH, E05. Archived from the original on June 25, 2018.
- ^ Dolgin, Elie (2021-04-01). "First GM pigs for allergies. Could xenotransplants be next?". Nature Biotechnology. 39 (4): 397–400. doi:10.1038/s41587-021-00885-9. ISSN 1546-1696. PMID 33846652. S2CID 233223010.
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- ^ DErcole FJ, Dhandha VH, Levi ML, et al. (2019). "Perioperative Challenges in Patients with Alpha-Gal Allergy". J Clin Anesth Pain Manag. 3 (1): 70–78. doi:10.36959/377/330.
Further reading
[edit]- Platts-Mills TA, Li RC, Keshavarz B, Smith AR, Wilson JM (2020). "Diagnosis and Management of Patients with the α-Gal Syndrome". J Allergy Clin Immunol Pract. 8 (1): 15–23. doi:10.1016/j.jaip.2019.09.017. PMC 6980324. PMID 31568928.
- McKenna, Maryn (December 11, 2018). "What is behind the spread of a mysterious allergy to meat?". The Guardian. Retrieved December 11, 2018.
- Surendra RS; Shahid Karim (2021). "Tick Saliva and the Alpha-Gal Syndrome: Finding a Needle in a Haystack". Frontiers in Cellular and Infection Microbiology. 11. doi:10.3389/fcimb.2021.680264. PMC 8331069. PMID 34354960.
- Surendra RS; Choudhary S; Vorobiov J; Commins SP J; Shahid Karim (2024). "Tick bite-induced alpha-gal syndrome and immunologic responses in an alpha-gal deficient murine model". Frontiers in Immunology. 14. doi:10.3389/fimmu.2023.1336883. PMC 10882631. PMID 38390396.
- Chung, Christine H.; Mirakhur, Beloo; Chan, Emily; Le, Quynh-Thu; Berlin, Jordan; Morse, Michael; Murphy, Barbara A.; Satinover, Shama M.; Hosen, Jacob; Mauro, David; Slebos, Robbert J.; Zhou, Qinwei; Gold, Diane; Hatley, Tina; Hicklin, Daniel J.; Platts-Mills, Thomas A.E. (13 March 2008). "Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose". New England Journal of Medicine. 358 (11): 1109–1117. doi:10.1056/NEJMoa074943. PMC 2361129.