ALPHA-GAL SYNDROME: AN EMERGING TICK-INDUCED ALLERGY TO MAMMALIAN MEAT – CURRENT KNOWLEDGE AND CLINICAL IMPLICATIONS
DOI:
https://doi.org/10.31435/ijitss.1(49).2026.5270Keywords:
Alpha-Gal Syndrome, Tick Bite, Red Meat Allergy, IgE, Delayed Anaphylaxis, Galactose-α-1,3-galactoseAbstract
Background: Alpha-gal syndrome (AGS) is an emerging IgE-mediated allergy to galactose-α-1,3-galactose (α-gal), a carbohydrate epitope present in most non-primate mammals. The condition is typically triggered by tick bites and is characterized by delayed hypersensitivity reactions occurring several hours after ingestion of mammalian meat or exposure to products containing α-gal. Increasing tick populations and environmental changes have contributed to the growing recognition of this condition worldwide.
Aim: This review aims to summarize current knowledge on the epidemiology, immunopathogenesis, clinical manifestations, diagnosis, and management of alpha-gal syndrome, with particular emphasis on its clinical implications and challenges in everyday medical practice.
Materials and methods: A narrative review of the literature was conducted using publications indexed in PubMed. Clinical studies, case series, mechanistic studies, and review articles published between 2009 and 2026 were included. The evidence was analyzed and synthesized across key thematic areas, including epidemiology, pathophysiology, clinical presentation, diagnostic approaches, and management strategies.
Results: AGS represents a unique model of delayed IgE-mediated food allergy. Clinical manifestations range from isolated gastrointestinal symptoms and urticaria to severe anaphylaxis. Diagnosis is primarily based on the detection of serum IgE antibodies to α-gal combined with a compatible clinical history. The cornerstone of management remains avoidance of mammalian-derived foods and prevention of further tick bites. Recent evidence also highlights the potential role of cofactors, biological therapies, and non-dietary exposures in triggering allergic reactions.
Conclusions: Alpha-gal syndrome is an increasingly recognized but still underdiagnosed allergic condition that poses significant diagnostic and clinical challenges. Greater awareness among clinicians and further research into the immunological mechanisms and long-term outcomes of the disease are essential to improve diagnosis and patient management.
References
Wilson, J. M., Erickson, L., Levin, M., Ailsworth, S. M., Commins, S. P., & Platts-Mills, T. A. E. (2024). Tick bites, IgE to galactose-alpha-1,3-galactose and urticarial or anaphylactic reactions to mammalian meat: The alpha-gal syndrome. Allergy, 79(6), 1440–1454. https://doi.org/10.1111/all.16003
Van Nunen, S. A., O'Connor, K. S., Clarke, L. R., Boyle, R. X., & Fernando, S. L. (2009). An association between tick bite reactions and red meat allergy in humans. The Medical Journal of Australia, 190(9), 510–511. https://doi.org/10.5694/j.1326-5377.2009.tb02533.x
Wilson, J. M., & Platts-Mills, T. A. (2018). The oligosaccharide galactose-α-1,3-galactose and the α-gal syndrome: Insights from an epitope that is causal in immunoglobulin E-mediated immediate and delayed anaphylaxis. EMJ Allergy Immunology, 3(1), 89–98.
McGill, S. K., Hashash, J. G., & Platts-Mills, T. A. (2023). AGA clinical practice update on alpha-gal syndrome for the GI clinician: Commentary. Clinical Gastroenterology and Hepatology, 21(4), 891–896. https://doi.org/10.1016/j.cgh.2022.12.035
Platts-Mills, T. A. E., Gangwar, R. S., Workman, L., & Wilson, J. M. (2025). The immunology of alpha-gal syndrome: History, tick bites, IgE, and delayed anaphylaxis to mammalian meat. Immunological Reviews, 332(1), e70035. https://doi.org/10.1111/imr.70035
Thompson, J. M., Carpenter, A., Kersh, G. J., Wachs, T., Commins, S. P., & Salzer, J. S. (2023). Geographic distribution of suspected alpha-gal syndrome cases—United States, January 2017–December 2022. MMWR. Morbidity and Mortality Weekly Report, 72(30), 815–820. https://doi.org/10.15585/mmwr.mm7230a2
Kiewiet, M. B. G., Apostolovic, D., Starkhammar, M., Grundström, J., Hamsten, C., & van Hage, M. (2020). Clinical and serological characterization of the α-gal syndrome-Importance of atopy for symptom severity in a European cohort. The Journal of Allergy and Clinical Immunology: In Practice, 8(6), 2027–2034.e2. https://doi.org/10.1016/j.jaip.2020.02.016
Leth-Møller, K. B., van Hage, M., Apostolovic, D., Sørensen, J. A., Vestergaard, C., Madsen, F., Kjær, L. J., Hansen, T., Jonsson, A., Thomsen, S. F., & Linneberg, A. (2025). Increasing prevalence of galactose-α-1,3-galactose sensitization in the Danish general adult population. Allergy, 80(1), 297–308. https://doi.org/10.1111/all.16360
Rutkowski, K., Sowa, P., Mroczko, B., Pancewicz, S., Rutkowski, R., Czupryna, P., Groblewska, M., Łukaszewicz-Zając, M., & Moniuszko-Malinowska, A. (2022). Sensitisation and allergic reactions to alpha-1,3-galactose in Podlasie, Poland, an area endemic for tick-borne infections. Infectious Diseases, 54(8), 572–579. https://doi.org/10.1080/23744235.2022.2057583
Hamsten, C., et al. (2013). Red meat allergy in Sweden: Association with tick sensitization. Journal of Allergy and Clinical Immunology.
Perusko, M., Grundström, J., Eldh, M., Hamsten, C., Apostolovic, D., & van Hage, M. (2024). The α-Gal epitope - the cause of a global allergic disease. Frontiers in Immunology, 15, 1335911. https://doi.org/10.3389/fimmu.2024.1335911
Galili, U. (2013). Anti-Gal: An abundant human natural antibody of multiple pathogeneses and clinical benefits. Immunology, 140(1), 1–11. https://doi.org/10.1111/imm.12110
Apostolovic, D., Grundström, J., Kiewiet, M. B. G., Perusko, M., Hamsten, C., Starkhammar, M., Paulie, S., & van Hage, M. (2023). Th2-skewed T cells correlate with B cell response to α-Gal and tick antigens in α-Gal syndrome. The Journal of Clinical Investigation, 133(6), e158357. https://doi.org/10.1172/JCI158357
Román-Carrasco, P., Hemmer, W., Cabezas-Cruz, A., Hodžić, A., de la Fuente, J., & Swoboda, I. (2021). The α-Gal syndrome and potential mechanisms. Frontiers in Allergy, 2, 783279. https://doi.org/10.3389/falgy.2021.783279
Sharma, S. R., Choudhary, S. K., Vorobiov, J., Commins, S. P., & Karim, S. (2024). Tick bite-induced alpha-gal syndrome and immunologic responses in an alpha-gal deficient murine model. Frontiers in Immunology, 14, 1336883. https://doi.org/10.3389/fimmu.2023.1336883
Carson, A. S., Gardner, A., & Iweala, O. I. (2022). Where's the beef? Understanding allergic responses to red meat in alpha-gal syndrome. Journal of Immunology, 208(2), 267–277. https://doi.org/10.4049/jimmunol.2100712
Kepley, C. L., Wang, Y., Yelton, A., Siebert, E. R., & Iweala, O. I. (2025). Ticked off: Allergic effector cells in the pathogenesis of alpha-gal syndrome. Current Allergy and Asthma Reports, 25(1), 57. https://doi.org/10.1007/s11882-025-01237-2
Morisset, M., Richard, C., Astier, C., Jacquenet, S., Croizier, A., Beaudouin, E., Cordebar, V., Morel-Codreanu, F., Petit, N., Moneret-Vautrin, D. A., & Kanny, G. (2012). Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose. Allergy, 67(5), 699–704. https://doi.org/10.1111/j.1398-9995.2012.02799.x
Chakrapani, N., Fischer, J., Swiontek, K., Codreanu-Morel, F., Hannachi, F., Morisset, M., Mugemana, C., Bulaev, D., Blank, S., Bindslev-Jensen, C., Biedermann, T., Ollert, M., & Hilger, C. (2022). α-Gal present on both glycolipids and glycoproteins contributes to immune response in meat-allergic patients. The Journal of Allergy and Clinical Immunology, 150(2), 396–405.e11. https://doi.org/10.1016/j.jaci.2022.02.030
Commins, S. P., Satinover, S. M., Hosen, J., Mozena, J., Borish, L., Lewis, B. D., Woodfolk, J. A., & Platts-Mills, T. A. (2009). Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. The Journal of Allergy and Clinical Immunology, 123(2), 426–433. https://doi.org/10.1016/j.jaci.2008.10.052
Reddy, S., Yi, L., Shields, B., Platts-Mills, T., Wilson, J., & Flowers, R. H. (2023). Alpha-gal syndrome: A review for the dermatologist. Journal of the American Academy of Dermatology, 89(4), 750–757. https://doi.org/10.1016/j.jaad.2023.04.054
Rao, S., Rathore, S. S., Goyal, R. M., Narakornpichit, A., Karkra, R., Al-Khazraji, A., & Grover, M. (2026). Understanding alpha-gal syndrome: A systematic review and meta-analysis of clinical manifestations and outcomes. Neurogastroenterology and Motility, 38(1), e70245. https://doi.org/10.1111/nmo.70245
Vernon, S. T., Kott, K. A., Hansen, T., Finemore, M., Baumgart, K. W., Bhindi, R., Yang, J., Hansen, P. S., Nicholls, S. J., Celermajer, D. S., Ward, M. R., van Nunen, S. A., Grieve, S. M., & Figtree, G. A. (2022). Immunoglobulin E sensitization to mammalian oligosaccharide galactose-α-1,3 (α-Gal) is associated with noncalcified plaque, obstructive coronary artery disease, and ST-segment-elevated myocardial infarction. Arteriosclerosis, Thrombosis, and Vascular Biology, 42(3), 352–361. https://doi.org/10.1161/ATVBAHA.121.316878
Fischer, J., Lupberger, E., Hebsaker, J., Blumenstock, G., Aichinger, E., Yazdi, A. S., Reick, D., Oehme, R., & Biedermann, T. (2017). Prevalence of type I sensitization to alpha-gal in forest service employees and hunters. Allergy, 72(10), 1540–1547. https://doi.org/10.1111/all.13156
McGill, S. K., Commins, S. P., Peery, A. F., Galanko, J., Keku, T. O., Shaheen, N. J., Anderson, C., & Sandler, R. S. (2023). Alpha-Gal sensitization in a US screening population is not associated with a decreased meat intake or gastrointestinal symptoms. The American Journal of Gastroenterology, 118(7), 1276–1281. https://doi.org/10.14309/ajg.0000000000002219
Mehlich, J., Fischer, J., Hilger, C., Swiontek, K., Morisset, M., Codreanu-Morel, F., Schiener, M., Blank, S., Ollert, M., Darsow, U., Biedermann, T., & Eberlein, B. (2019). The basophil activation test differentiates between patients with alpha-gal syndrome and asymptomatic alpha-gal sensitization. The Journal of Allergy and Clinical Immunology, 143(1), 182–189. https://doi.org/10.1016/j.jaci.2018.06.049
Naseem, Z., Muhammad, A., Chatterjee, A., & Rubio-Tapia, A. (2025). Alpha-gal syndrome: Recognizing and managing a tick-bite-related meat allergy. Cleveland Clinic Journal of Medicine, 92(5), 311–319. https://doi.org/10.3949/ccjm.92a.24072
Patel, C., & Iweala, O. I. (2020). 'Doc, will I ever eat steak again?': Diagnosis and management of alpha-gal syndrome. Current Opinion in Pediatrics, 32(6), 816–824. https://doi.org/10.1097/MOP.0000000000000955
Awosika, A., & Balaji, P. (2026). Misdiagnosis of alpha-gal syndrome as non-celiac gluten sensitivity or lactose intolerance: A diagnostic blind spot for clinicians. World Journal of Gastroenterology, 32(3), 116350. https://doi.org/10.3748/wjg.v32.i3.116350
Kim, M. S., Straesser, M. D., Keshavarz, B., Workman, L., McGowan, E. C., Platts-Mills, T. A. E., & Wilson, J. M. (2020). IgE to galactose-α-1,3-galactose wanes over time in patients who avoid tick bites. The Journal of Allergy and Clinical Immunology: In Practice, 8(1), 364–367.e2. https://doi.org/10.1016/j.jaip.2019.08.045
Iglesia, E. G. A., Kwan, M., Virkud, Y. V., & Iweala, O. I. (2024). Management of food allergies and food-related anaphylaxis. JAMA, 331(6), 510–521. https://doi.org/10.1001/jama.2023.26857
Emerson, A. G., Mundy, L., Murphy, B. A., & Stone, C. A. (2026). Cetuximab hypersensitivity in the setting of asymptomatic alpha-gal sensitization. Head & Neck, 48(3), E33–E36. https://doi.org/10.1002/hed.70030
Chinuki, Y., & Morita, E. (2019). Alpha-Gal-containing biologics and anaphylaxis. Allergology International, 68(3), 296–300. https://doi.org/10.1016/j.alit.2019.04.001
Mullins, R. J., James, H., Platts-Mills, T. A., & Commins, S. (2012). Relationship between red meat allergy and sensitization to gelatin and galactose-α-1,3-galactose. The Journal of Allergy and Clinical Immunology, 129(5), 1334–1342.e1. https://doi.org/10.1016/j.jaci.2012.02.038
Uyttebroek, A., Sabato, V., Bridts, C. H., De Clerck, L. S., & Ebo, D. G. (2014). Anaphylaxis to succinylated gelatin in a patient with a meat allergy: Galactose-α(1, 3)-galactose (α-gal) as antigenic determinant. Journal of Clinical Anesthesia, 26(7), 574–576. https://doi.org/10.1016/j.jclinane.2014.04.014
Hawkins, R. B., Wilson, J. M., Mehaffey, J. H., Platts-Mills, T. A. E., & Ailawadi, G. (2021). Safety of intravenous heparin for cardiac surgery in patients with alpha-gal syndrome. The Annals of Thoracic Surgery, 111(6), 1991–1997. https://doi.org/10.1016/j.athoracsur.2020.07.050
Zvara, J., Smith, A. L., Mazzeffi, M. A., Kleiman, A. M., Tanaka, K., Smith, A. R., Wilson, J. M., & McNeil, J. S. (2024). Alpha-gal syndrome and cardiac surgery. Journal of Cardiothoracic and Vascular Anesthesia, 38(11), 2805–2811. https://doi.org/10.1053/j.jvca.2024.07.035
Swiontek, K., Morisset, M., Codreanu-Morel, F., Fischer, J., Mehlich, J., Darsow, U., Petitpain, N., Biedermann, T., Ollert, M., Eberlein, B., & Hilger, C. (2019). Drugs of porcine origin-A risk for patients with α-gal syndrome? The Journal of Allergy and Clinical Immunology: In Practice, 7(5), 1687–1690.e3. https://doi.org/10.1016/j.jaip.2018.12.005
Muglia, C., Kar, I., Gong, M., Hermes-DeSantis, E. R., & Monteleone, C. (2015). Anaphylaxis to medications containing meat byproducts in an alpha-gal sensitized individual. The Journal of Allergy and Clinical Immunology: In Practice, 3(5), 796–797. https://doi.org/10.1016/j.jaip.2015.04.004
Dunkman, W. J., Rycek, W., & Manning, M. W. (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. https://doi.org/10.1213/ANE.0000000000003460
Vidal, C., Méndez-Brea, P., López-Freire, S., & González-Vidal, T. (2016). Vaginal capsules: An unsuspected probable source of exposure to α-Gal. Journal of Investigational Allergology & Clinical Immunology, 26(6), 388–389. https://doi.org/10.18176/jiaci.0105
Stone, C. A., Jr, Hemler, J. A., Commins, S. P., Schuyler, A. J., Phillips, E. J., Peebles, R. S., Jr, & Fahrenholz, J. M. (2017). Anaphylaxis after zoster vaccine: Implicating alpha-gal allergy as a possible mechanism. The Journal of Allergy and Clinical Immunology, 139(5), 1710–1713.e2. https://doi.org/10.1016/j.jaci.2016.10.037
Retterer, M. K. C., Workman, L. J., Bacon, J. R., & Platts-Mills, T. A. E. (2018). Specific IgE to gelatin as a cause of anaphylaxis to zoster vaccine. The Journal of Allergy and Clinical Immunology, 141(5), 1956–1957. https://doi.org/10.1016/j.jaci.2017.08.047
Stone, C. A., Jr, Commins, S. P., Choudhary, S., Vethody, C., Heavrin, J. L., Wingerter, J., Hemler, J. A., Babe, K., Phillips, E. J., & Norton, A. E. (2019). Anaphylaxis after vaccination in a pediatric patient: Further implicating alpha-gal allergy. The Journal of Allergy and Clinical Immunology: In Practice, 7(1), 322–324.e2. https://doi.org/10.1016/j.jaip.2018.06.005
Mozzicato, S. M., Tripathi, A., Posthumus, J. B., Platts-Mills, T. A. E., & Commins, S. P. (2014). Porcine or bovine valve replacement in 3 patients with IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose. The Journal of Allergy and Clinical Immunology: In Practice, 2(5), 637–638. https://doi.org/10.1016/j.jaip.2014.04.016
Mangold, A., Szerafin, T., Hoetzenecker, K., Hacker, S., Lichtenauer, M., Niederpold, T., Nickl, S., Dworschak, M., Blumer, R., Auer, J., & Ankersmit, H. J. (2009). Alpha-Gal specific IgG immune response after implantation of bioprostheses. The Thoracic and Cardiovascular Surgeon, 57(4), 191–195. https://doi.org/10.1055/s-0029-1185395
Hawkins, R. B., Frischtak, H. L., Kron, I. L., & Ghanta, R. K. (2016). Premature bioprosthetic aortic valve degeneration associated with allergy to galactose-alpha-1,3-galactose. Journal of Cardiac Surgery, 31(7), 446–448. https://doi.org/10.1111/jocs.12764
McGregor, C., Byrne, G., Rahmani, B., Chisari, E., Kyriakopoulou, K., & Burriesci, G. (2016). Physical equivalency of wild type and galactose α 1,3 galactose free porcine pericardium; A new source material for bioprosthetic heart valves. Acta Biomaterialia, 41, 204–209. https://doi.org/10.1016/j.actbio.2016.06.007
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Iga Kałka, Julia Szmuc, Natalia Kaczmarczyk, Jakub Robert Skalski, Karolina Halat, Antoni Hajdas, Gabriela Daniel, Łukasz Ćmok, Justyna Chudy, Julia Dobrowolska
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
How to Cite
