Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS)

References

• Hils M, Wölbing F, Hilger C, Fischer J, Hoffard N, Biedermann T. The history of carbohydrates in type I allergy. Front Immunol. 2020;11(10):1–14. doi:10.3389/fimmu.2020.586924
   PubMed Web of Science ®Google Scholar
• Hilger C, Fischer J, Wölbing F, Biedermann T. Role and mechanism of Galactose-Alpha-1,3-Galactose in the elicitation of delayed anaphylactic reactions to red meat. Curr Allergy and Asthma Rep. 2019;19(1):1–11. doi:10.1007/s11882-019-0835-9
   PubMed Web of Science ®Google Scholar
• Galili U. Evolution in primates by “Catastrophic-selection” interplay between enveloped virus epidemics, mutated genes of enzymes synthesizing carbohydrate antigens, and natural anti-carbohydrate antibodies. Am J Phys Anthropol. 2019;168(2):352–363. doi:10.1002/ajpa.23745
   PubMed Web of Science ®Google Scholar
• Commins SP, Satinover SM, Hosen J, et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose. J Allergy Clin Immunol. 2009;123(2):426–433.e2. doi:10.1016/j.jaci.2008.10.052
   PubMed Web of Science ®Google Scholar
• Fischer J, Yazdi AS, Biedermann T. Clinical spectrum of α-Gal syndrome: from immediate-type to delayed immediate-type reactions to mammalian innards and meat. Allergo J Int. 2016;25(2):55–62. doi:10.1007/s40629-016-0099-z
   PubMedGoogle Scholar
• Çelebioğlu E, Akarsu A, Şahiner ÜM. IgE mediated food allergy throughout the life. Turk J Med Sci. 2021;51(1):49–60. doi:10.3906/sag-2006-95
   PubMed Web of Science ®Google Scholar
• Fischer J, Reepschläger T, Schricker T, Raap U. Alpha-gal syndrome: overview of clinical presentation and pathophysiology. Hautarzt. 2022;73(3):195–200. doi:10.1007/s00105-022-04943-4
   PubMed Web of Science ®Google Scholar
• Chinuki Y, Takahashi H, Morita E. IgE antibodies to galactose-α-1,3-galactose, an epitope of red meat allergen, cross-react with a novel flounder roe allergen. J Investig Allergol Clin Immunol. 2021;32(4):1–7. doi:10.18176/jiaci.0754
   Web of Science ®Google Scholar
• Dunkman WJ, Rycek W, Manning MW. What does a red meat allergy have to do with anesthesia? Perioperative management of alpha-gal syndrome. Anesth Analg. 2019;129(5):1242–1248. doi:10.1213/ANE.0000000000003460
   PubMed Web of Science ®Google Scholar
• Cabezas-Cruz A, Hodžić A, Román-Carrasco P, et al. Environmental and molecular drivers of the α-Gal syndrome. Front Immunol. 2019;10(5):1–12. doi:10.3389/fimmu.2019.01210
   PubMed Web of Science ®Google Scholar
• Cabezas-Cruz A, Valdés J, de la Fuente J. Cancer research meets tick vectors for infectious diseases. Lancet Infect Dis. 2014;14(10):916–917. doi:10.1016/S1473-3099(14)70902-8
   PubMed Web of Science ®Google Scholar
• Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for Galactose-α-1,3-Galactose. N Engl J Med. 2008;358(11):1109–1117. doi:10.1056/nejmoa074943
   PubMed Web of Science ®Google Scholar
• de la Fuente J, Pacheco I, Villar M, Cabezas-Cruz A. The alpha-Gal syndrome: new insights into the tick-host conflict and cooperation. Parasit Vectors. 2019;12(1):1–5. doi:10.1186/s13071-019-3413-z
   PubMed Web of Science ®Google Scholar
• Rodríguez Y, Rojas M, Gershwin ME, Anaya JM. Tick-borne diseases and autoimmunity: a comprehensive review. J Autoimmun. 2018;88(3):21–42. doi:10.1016/j.jaut.2017.11.007
   PubMed Web of Science ®Google Scholar
• Cabezas-Cruz A, Mateos-Hernández L, Chmelař J, Villar M, de la Fuente J. Salivary prostaglandin E2: role in tick-induced allergy to red meat. Trends Parasitol. 2017;33(7):495–498. doi:10.1016/j.pt.2017.03.004
   PubMed Web of Science ®Google Scholar
• Román-Carrasco P, Hemmer W, Cabezas-Cruz A, Hodžić A, de la Fuente J, Swoboda I. The α-Gal syndrome and potential mechanisms. Front Allergy. 2021;2(12):1–17. doi:10.3389/falgy.2021.783279
   Google Scholar
• Ramasamy R. Mosquito vector proteins homologous to α1-3 galactosyl transferases of tick vectors in the context of protective immunity against malaria and hypersensitivity to vector bites. Parasit Vectors. 2021;14(1):1–6. doi:10.1186/s13071-021-04801-7
   PubMed Web of Science ®Google Scholar
• Wilson JM, Schuyler AJ, Schroeder N, Platts-Mills TAE. Galactose-α-1,3-Galactose: atypical food allergen or model IgE hypersensitivity? Curr Allergy Asthma Rep. 2017;17(1):3–9. doi:10.1007/s11882-017-0672-7
   PubMed Web of Science ®Google Scholar
• Cabezas-Cruz A, Hodžić A, Mateos-Hernandez L, Contreras M, De La Fuente J. Tick-human interactions: from allergic klendusity to the α-Gal syndrome. Biochem J. 2021;478(9):1783–1794. doi:10.1042/BCJ20200915
   PubMed Web of Science ®Google Scholar
• Carson AS, Gardner A, Iweala OI. Where’s the beef? Understanding allergic responses to red meat in alpha-gal syndrome. J Immunol. 2022;208(2):267–277. doi:10.4049/jimmunol.2100712
   PubMed Web of Science ®Google Scholar
• Wong XL, Sebaratnam DF. Mammalian meat allergy. Int J Dermatol. 2018;57(12):1433–1436. doi:10.1111/ijd.14208
   PubMed Web of Science ®Google Scholar
• Young I, Prematunge C, Pussegoda K, Corrin T, Waddell L. Tick exposures and alpha-gal syndrome: a systematic review of the evidence. Ticks Tick Borne Dis. 2021;12(3):101674. doi:10.1016/j.ttbdis.2021.101674
   PubMed Web of Science ®Google Scholar
• Diaz JH. Red meat allergies after Lone Star tick (Amblyomma americanum) bites. South Med J. 2020;113(6):267–274. doi:10.14423/SMJ.0000000000001102
   PubMed Web of Science ®Google Scholar
• van Nunen S. Tick-induced allergies: mammalian meat allergy, tick anaphylaxis and their significance. Asia Pac Allergy. 2015;5(1):3–16. doi:10.5415/apallergy.2015.5.1.3
   PubMedGoogle Scholar
• Platts-Mills TAE, Commins SP, Biedermann T, et al. On the cause and consequences of IgE to galactose-α-1,3-galactose: a report from the National Institute of Allergy and Infectious Diseases Workshop on understanding IgE-mediated mammalian meat allergy. J Allergy Clin Immunol. 2020;145(4):1061–1071. doi:10.1016/j.jaci.2020.01.047
   PubMed Web of Science ®Google Scholar
• Joral A, Azketa N, Sanchez P, et al. The quantification of IgG specific to α-Gal could be used as a risk marker for suffering mammalian meat allergy. Foods. 2022;11(3):466. doi:10.3390/foods11030466
   PubMed Web of Science ®Google Scholar
• McGain F, Welton R, Solley GO, Winkel KD. First fatalities from tick bite anaphylaxis. J Allergy Clin Immunol Pract. 2016;2(7):309–314. doi:10.1080/21674086.1933.11925177
   Google Scholar
• Mullins RJ, Wainstein BK, Barnes EH, Liew WK, Campbell DE. Increases in anaphylaxis fatalities in Australia from 1997 to 2013. Clin Exp Allergy. 2016;46(8):1099–1110. doi:10.1111/cea.12748
   PubMed Web of Science ®Google Scholar
• Commins SP. Invited commentary: alpha-gal allergy: tip of the iceberg to a pivotal immune response. Curr Allergy Asthma Rep. 2016;16(9):1–3. doi:10.1007/s11882-016-0641-6
   PubMed Web of Science ®Google Scholar
• Levin M, Apostolovic D, Biedermann T, et al. Galactose α-1,3-galactose phenotypes: lessons from various patient populations. Ann Allergy Asthma Immunol. 2019;122(6):598–602. doi:10.1016/j.anai.2019.03.021
   PubMed Web of Science ®Google Scholar
• Zurbano-Azqueta L, Antón-Casas E, Duque-Gómez S, Jiménez-Gómez I, Fernández-Pellón L, López-Gutiérrez J. Alpha-gal syndrome. Allergy to red meat and gelatin. Rev Clin Esp. 2021. doi:10.1016/j.rceng.2021.06.005
   PubMedGoogle Scholar
• Mateo-Borrega MB, Garcia B, Larramendi CH, et al. Ige-mediated sensitization to galactose-α-1,3-galactose (α-gal) in urticaria and anaphylaxis in Spain: geographical variations and risk factors. J Investig Allergol Clin Immunol. 2019;29(6):436–443. doi:10.18176/jiaci.0373
   PubMed Web of Science ®Google Scholar
• Fischer J, Lupberger E, Hebsaker J, et al. Prevalence of type I sensitization to alpha-gal in forest service employees and hunters. Allergy. 2017;72(10):1540–1547. doi:10.1111/all.13156
   PubMed Web of Science ®Google Scholar
• Villalta D, Pantarotto L, Da Re M, et al. High prevalence of sIgE to Galactose-α1,3-galactose in rural pre-Alps area: a cross-sectional study. Clin Exp Allergy. 2016;46(2):377–380. doi:10.1111/cea.12655
   PubMed Web of Science ®Google Scholar
• Mitchell CL, Lin FC, Vaughn M, Apperson CS, Meshnick SR, Commins SP. Association between Lone Star tick bites and increased alpha-gal sensitization: evidence from a prospective cohort of outdoor workers. Parasit Vectors. 2020;13(1):1–4. doi:10.1186/s13071-020-04343-4
   PubMed Web of Science ®Google Scholar
• Venturini M, Lobera T, Sebastián A, Portillo A, Oteo JA. IgE to α-Gal in foresters and forest workers from La Rioja, North of Spain. J Investig Allergol Clin Immunol. 2018;28(2):106–112. doi:10.18176/jiaci.0218
   PubMed Web of Science ®Google Scholar
• Cabezas-Cruz A, de la Fuente J, Fischer J. Prevalence of type I sensitization to alpha-gal in forest service employees and hunters: is the blood type an overlooked risk factor in epidemiological studies of the α-Gal syndrome? Allergy. 2017;72(12):2044–2047. doi:10.1111/all.13206
   PubMed Web of Science ®Google Scholar
• Cabezas-Cruz A, Mateos-Hernández L, Alberdi P, et al. Effect of blood type on anti-a-Gal immunity and the incidence of infectious diseases. Exp Mol Med. 2017;49(3):e301–e301. doi:10.1038/emm.2016.164
   PubMed Web of Science ®Google Scholar
• Yilmaz B, Portugal S, Tran TM, et al. Gut microbiota elicits a protective immune response against malaria transmission. Cell. 2014;159(6):1277–1289. doi:10.1016/j.cell.2014.10.053
   PubMed Web of Science ®Google Scholar
• Urra JM, Ferreras-Colino E, Contreras M, et al. The antibody response to the glycan α-Gal correlates with COVID-19 disease symptoms. J Med Virol. 2021;93(4):2065–2075. doi:10.1002/jmv.26575
   PubMed Web of Science ®Google Scholar
• Steinke JW, Platts-Mills TAE, Commins SP. The alpha-gal story: lessons learned from connecting the dots. J Allergy Clin Immunol. 2015;135(3):589–596. doi:10.1016/j.jaci.2014.12.1947
   PubMed Web of Science ®Google Scholar
• Commins SP. Diagnosis & management of alpha-gal syndrome: lessons from 2500 patients. Expert Rev Clin Immunol. 2020;16(7):667–677. doi:10.1080/1744666X.2020.1782745
   PubMed Web of Science ®Google Scholar
• Lopes JP, Sicherer S. Food allergy: epidemiology, pathogenesis, diagnosis, prevention, and treatment. Curr Opin Immunol. 2020;66:57–64. doi:10.1016/j.coi.2020.03.014
   PubMed Web of Science ®Google Scholar
• Antunes J, Borrego L, Romeira A, Pinto P. Skin prick tests and allergy diagnosis. Allergol Immunopathol. 2009;37(3):155–164. doi:10.1016/S0301-0546(09)71728-8
   PubMed Web of Science ®Google Scholar
• Shroba J, Rath N, Barnes C. Possible role of environmental factors in the development of food allergies. Clin Rev Allergy Immunol. 2019;57(3):303–311. doi:10.1007/s12016-018-8703-2
   PubMed Web of Science ®Google Scholar
• Jacquenet S, Moneret-Vautrin DA, Bihain BE. Mammalian meat-induced anaphylaxis: clinical relevance of anti-galactose-α-1,3-galactose IgE confirmed by means of skin tests to cetuximab. J Allergy Clin Immunol. 2009;124(3):603–605. doi:10.1016/j.jaci.2009.06.014
   PubMed Web of Science ®Google Scholar
• Mateos-Hernández L, Villar M, Moral A, et al. Tick-host conflict: immunoglobulin E antibodies to tick proteins in patients with anaphylaxis to tick bite. Oncotarget. 2017;8(13):20630–20644. doi:10.18632/oncotarget.15243
   PubMedGoogle Scholar
• Hocaoglu AB, Cipe F, Aydogmus C. Are skin prick tests really safe? A case of anaphylaxis caused by skin prick testing with inhalant allergens. Allergol Immunopathol. 2015;43(2):215–216. doi:10.1016/j.aller.2013.09.011
   PubMed Web of Science ®Google Scholar
• Alnæs M. Anaphylaxis following prick-by-prick testing with peanut. Clin Case Rep. 2020;8(12):2366–2368. doi:10.1002/ccr3.3154
   PubMed Web of Science ®Google Scholar
• Chiriac AM, Bousquet J, Demoly P. In vivo methods for the study and diagnosis of allergy. In: Burks AW, Holgate ST, O´Hehir RE, et al. editors. Middleton’s Allergy: Principles and Practice. 9th ed. Elsevier; 2020:1119–1132. doi:10.1016/B978-0-323-08593-9.00071-1
   Google Scholar
• Calvani M, Bianchi A, Reginelli C, Peresso M, Testa A. Oral food challenge. Medicina. 2019;55(10):1–16. doi:10.3390/medicina55100651
   Web of Science ®Google Scholar
• de la Fuente J, Cabezas-Cruz A, Pacheco I. Alpha-gal syndrome: challenges to understanding sensitization and clinical reactions to alpha-gal. Expert Rev Mol Diagn. 2020;20(9):905–911. doi:10.1080/14737159.2020.1792781
   PubMed Web of Science ®Google Scholar
• Mehlich J, Fischer J, Hilger C, et al. The basophil activation test differentiates between patients with alpha-gal syndrome and asymptomatic alpha-gal sensitization. J Allergy Clin Immunol. 2019;143(1):182–189. doi:10.1016/j.jaci.2018.06.049
   PubMed Web of Science ®Google Scholar
• Mabelane T, Basera W, Botha M, Thomas HF, Ramjith J, Levin ME. 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. Pediatr Allergy Immunol. 2018;29(8):841–849. doi:10.1111/pai.12969
   PubMed Web of Science ®Google Scholar
• Eberlein B, Mehlich J, Reidenbach K, et al. Negative oral provocation test with porcine pancreatic enzyme plus cofactors despite confirmed α-gal syndrome. J Investig Allergol Clin Immunol. 2020;30(6):468–469. doi:10.18176/jiaci.0513
   PubMed Web of Science ®Google Scholar
• Morisset M, Richard C, Astier C, et al. Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose. Allergy. 2012;67(5):699–704. doi:10.1111/j.1398-9995.2012.02799.x
   PubMed Web of Science ®Google Scholar
• Fischer J, Biedermann T. Delayed immediate-type hypersensitivity to red meat and innards: current insights into a novel disease entity. J Dtsch Dermatol Ges. 2016;14(1):38–43. doi:10.1111/ddg.12821
   PubMed Web of Science ®Google Scholar
• Jappe U, Minge S, Kreft B, et al. Meat allergy associated with galactosyl-α-(1,3)-galactose (α-Gal)-Closing diagnostic gaps by anti-α-Gal IgE immune profiling. Allergy. 2018;73(1):93–105. doi:10.1111/all.13238
   PubMed Web of Science ®Google Scholar
• Leung DYM, Szefler SJ. Tick bites: a common cause of IgE antibodies to alpha-gal. J Allergy Clin Immunol. 2011;127(5):1131–1132. doi:10.1016/j.jaci.2011.03.019
   Google Scholar
• Chinuki Y, Morita E. Alpha-Gal-containing biologics and anaphylaxis. Allergol Int. 2019;68(3):296–300. doi:10.1016/j.alit.2019.04.001
   PubMed Web of Science ®Google Scholar
• Mabelane T, Ogunbanjo GA. Ingestion of mammalian meat and alpha-gal allergy: clinical relevance in primary care. Afr J Prim Health Care Fam Med. 2019;11(1):1–5. doi:10.4102/phcfm.v11i1.1901
   PubMed Web of Science ®Google Scholar
• Park Y, Kim D, Boorgula GD, et al. Alpha-gal and cross-reactive carbohydrate determinants in the N-Glycans of salivary glands in the Lone Star Tick, Amblyomma americanum. Vaccines. 2020;8(1):1–16. doi:10.3390/vaccines8010018
   Web of Science ®Google Scholar
• Apostolovic D, Grundström J, Perusko M, et al. Course of IgE to α-Gal in a Swedish population of α-Gal syndrome patients. Clin Transl Allergy. 2021;11(10):2–4. doi:10.1002/clt2.12087
   Web of Science ®Google Scholar
• Gonzalez-Quintela A, Dam Laursen AS, Vidal C, Skaaby T, Gude F, Linneberg A. IgE antibodies to alpha-gal in the general adult population: relationship with tick bites, atopy, and cat ownership. Clin Exp Allergy. 2014;44(8):1061–1068. doi:10.1111/cea.12326
   PubMed Web of Science ®Google Scholar
• Wilson JM, Keshavarz B, Retterer M, et al. A dynamic relationship between two regional causes of IgE-mediated anaphylaxis: α-Gal syndrome and imported fire ant. J Allergy Clin Immunol. 2021;147(2):643–652.e7. doi:10.1016/j.jaci.2020.05.034
   PubMed Web of Science ®Google Scholar
• Passanisi S, Lombardo F, Crisafulli G, Salzano G, Aversa T, Pajno GB. Novel diagnostic techniques and therapeutic strategies for IgE-mediated food allergy. Allergy Asthma Proc. 2021;42(2):124–130. doi:10.2500/AAP.2021.42.200129
   PubMed Web of Science ®Google Scholar
• Foong RX, Santos AF. Biomarkers of diagnosis and resolution of food allergy. Pediatr Allergy Immunol. 2021;32(2):223–233. doi:10.1111/pai.13389
   PubMed Web of Science ®Google Scholar
• Fernandez-Santamaria R, Bogas G, Salas M, et al. The role of basophil activation test in drug allergy. Curr Treat Options Allergy. 2021;8(4):298–313. doi:10.1007/s40521-021-00294-y
   Google Scholar
• Schmidle P, Eberlein B, Darsow U, Kugler C, Biedermann T, Brockow K. α-Gal-Syndrom – nicht nur eine Fleischallergie. Allergologie. 2021;44(4):288–296. doi:10.5414/ALX02185
   Web of Science ®Google Scholar
• Santos AF, Kulis MD, Sampson HA. Bringing the next generation of food allergy diagnostics into the clinic. J Allergy Clin Immunol Pract. 2022;10(1):1–9. doi:10.1016/j.jaip.2021.09.009
   PubMed Web of Science ®Google Scholar
• Santos AF, Lack G. Basophil activation test: food challenge in a test tube or specialist research tool? Clin Transl Allergy. 2016;6(1):1–9. doi:10.1186/s13601-016-0098-7
   PubMed Web of Science ®Google Scholar
• Wilson JM, Platts-Mills TAE. IgE to galactose-α-1,3-galactose and the α-Gal syndrome: insights from basophil activation testing. J Allergy Clin Immunol. 2018;143(1):101–103. doi:10.1016/j.jaci.2018.10.029
   PubMed Web of Science ®Google Scholar
• Doña I, Ariza A, Fernández TD, Torres MJ. Basophil activation test for allergy diagnosis. J Vis Exp. 2021;171(5):e62600. doi:10.3791/62600
   Web of Science ®Google Scholar
• Ebo DG, Bridts CH, Mertens CH, et al. Principles, potential, and limitations of ex vivo basophil activation by flow cytometry in allergology: a narrative review. J Allergy Clin Immunol. 2021;147(4):1143–1153. doi:10.1016/j.jaci.2020.10.027
   PubMed Web of Science ®Google Scholar
• Santos AF, Alpan O, Hoffmann HJ. Basophil activation test: mechanisms and considerations for use in clinical trials and clinical practice. Allergy. 2021;76(11):2420–2432. doi:10.1111/all.14747
   PubMed Web of Science ®Google Scholar
• Directive 98/79/EC on in vitro diagnostic medical devices; 1998. Available from: http://data.europa.eu/eli/dir/1998/79/oj. Accessed June 22, 2022.
   Google Scholar
• Regulation (EU) 2017/746 on in vitro diagnostic medical devices; 2022. Available from: http://data.europa.eu/eli/reg/2017/746/2022-01-28. Accessed June 22, 2022.
   Google Scholar
• Bahri R, Bulfone-Paus S. Mast Cell Activation Test (MAT). Methods Mol Biol. 2020;2163:227–238. doi:10.1007/978-1-0716-0696-4_19
   PubMedGoogle Scholar
• Bahri R, Custovic A, Korosec P, et al. Mast cell activation test in the diagnosis of allergic disease and anaphylaxis. J Allergy Clin Immunol. 2018;142(2):485–496.e16. doi:10.1016/j.jaci.2018.01.043
   PubMed Web of Science ®Google Scholar
• Chirumbolo S, Bjørklund G, Sboarina A, Vella A. The role of basophils as innate immune regulatory cells in allergy and immunotherapy. Hum Vaccines Immunother. 2018;14(4):815–831. doi:10.1080/21645515.2017.1417711
   PubMed Web of Science ®Google Scholar
• Elst J, Sabato V, van der Poorten MLM, et al. Basophil and mast cell activation tests by flow cytometry in immediate drug hypersensitivity: diagnosis and beyond. J Immunol Methods. 2021;495(4):113050. doi:10.1016/j.jim.2021.113050
   PubMed Web of Science ®Google Scholar
• Elst J, van der Poorten M-LM, van Gasse AL, et al. Mast cell activation tests by flow cytometry: a new diagnostic asset? Clin Exp Allergy. 2021;51(11):1482–1500. doi:10.1111/cea.13984
   PubMed Web of Science ®Google Scholar
• Kirshenbaum AS, Yin Y, Bruce Sundstrom J, Bandara G, Metcalfe DD. Description and characterization of a novel human mast cell line for scientific study. Int J Mol Sci. 2019;20(22):5520. doi:10.3390/ijms20225520
   PubMed Web of Science ®Google Scholar
• Chirumbolo S, Bjørklund G, Vella A. Mast cell activation test versus basophil activation test and related competing issues. J Allergy Clin Immunol. 2018;142(3):1018–1019. doi:10.1016/j.jaci.2018.06.020
   PubMed Web of Science ®Google Scholar
• Gray CL. Current controversies and future prospects for peanut allergy prevention, diagnosis and therapies. J Asthma Allergy. 2020;13:51–66. doi:10.2147/JAA.S196268
   PubMed Web of Science ®Google Scholar
• Larsen LF, Juel-Berg N, Hansen KS, et al. A comparative study on basophil activation test, histamine release assay, and passive sensitization histamine release assay in the diagnosis of peanut allergy. Allergy. 2018;73(1):137–144. doi:10.1111/all.13243
   PubMed Web of Science ®Google Scholar
• de la Fuente J, Pacheco I, Contreras M, Mateos-Hernández L, Villar M, Cabezas-Cruz A. Guillain-Barré and alpha-gal syndromes: saccharides-induced immune responses. Explor Res Hypothesis Med. 2019;4(4):87–89. doi:10.14218/erhm.2019.00027
   Google Scholar
• Villar M, Pacheco I, Mateos-Hernández L, et al. Characterization of tick salivary gland and saliva alphagalactome reveals candidate alpha-gal syndrome disease biomarkers. Expert Rev Proteomics. 2021;18(12):1099–1116. doi:10.1080/14789450.2021.2018305
   PubMed Web of Science ®Google Scholar
• Cabezas-Cruz A, Mateos-Hernández L, Pérez-Cruz M, et al. Regulation of the immune response to α-Gal and vector-borne diseases. Trends Parasitol. 2015;31(10):470–476. doi:10.1016/j.pt.2015.06.016
   PubMed Web of Science ®Google Scholar
• Richens JG, Lee CM, Johri S. Improving the accuracy of medical diagnosis with causal machine learning. Nat Commun. 2020;11:3923. doi:10.1038/s41467-020-17419-7
   PubMed Web of Science ®Google Scholar
• Geng W, Qin X, Yang T, et al. Model-based reasoning of clinical diagnosis in integrative medicine: real-world methodological study of electronic medical records and natural language processing methods. JMIR Med Inform. 2020;8(12):e23082. doi:10.2196/23082
   PubMed Web of Science ®Google Scholar
• Saretta F, Giovannini M, Mori F, et al. Alpha-gal syndrome in children: peculiarities of a “Tick-Borne” allergic disease. Front Pediatr. 2021;9(12). doi:10.3389/fped.2021.801753
   PubMed Web of Science ®Google Scholar
• Wilson JM, Platts-Mills TAE. Red meat allergy in children and adults. Curr Opin Allergy Clin Immunol. 2019;19(3):229–235. doi:10.1097/ACI.0000000000000523
   PubMed Web of Science ®Google Scholar
• Platts-Mills TAE, Li R, Keshavarz B, Smith AR, Wilson JM. Diagnosis and management of patients with the α-Gal syndrome. J Allergy Clin Immunol Pract. 2020;8(1):15–23. doi:10.1016/j.jaip.2019.09.017
   PubMed Web of Science ®Google Scholar
• Nwamara U, Kaplan MC, Mason N, Ingemi AI. A retrospective evaluation of heparin product reactions in patients with alpha-gal allergies. Ticks Tick Borne Dis. 2022;13(1):101869. doi:10.1016/j.ttbdis.2021.101869
   PubMed Web of Science ®Google Scholar
• Wen S, Unuma K, Chinuki Y, Hikino H, Uemura K. Fatal anaphylaxis due to alpha-gal syndrome after initial cetuximab administration: the first forensic case report. Leg Med. 2021;51(3):101878. doi:10.1016/j.legalmed.2021.101878
   PubMed Web of Science ®Google Scholar
• McHugh K, Repanshek Z. Anaphylaxis: emergency Department Treatment. Emerg Med Clin North Am. 2022;40(1):19–32. doi:10.1016/j.emc.2021.08.004
   PubMed Web of Science ®Google Scholar
• Lee YH, Kasper LH. Immune responses of different mouse strains after challenge with equivalent lethal doses of Toxoplasma gondii. Parasite. 2004;11:89–97. doi:10.1051/parasite/200411189
   PubMed Web of Science ®Google Scholar
• Daripa B, Lucchese S. Novel case presentation of abulia after Lone Star tick bite as evidenced by raised titers of alpha-gal specific IgM immunoglobulin and a possibility of alpha-gal driven hypothalamic dysfunction as the pathomechanism. Cureus. 2022;14(4):e24551. doi:10.7759/cureus.24551
   PubMed Web of Science ®Google Scholar
• Wuerdeman MF, Harrison JM. A case of tick-bite-induced red meat allergy. Mil Med. 2014;179(4):e473–e475. doi:10.7205/MILMED-D-13-00369
   PubMedGoogle Scholar
• Jackson WL. Mammalian meat allergy following a tick bite: a case report. Oxf Med Case Rep. 2018;2018(2):58–60. doi:10.1093/omcr/omx098
   Web of Science ®Google Scholar
• Kaplan AC, Carson MP. Diagnosing meat allergy after tick bite without delay. J Am Board Fam Med. 2018;31(4):650–652. doi:10.3122/jabfm.2018.04.170425
   PubMed Web of Science ®Google Scholar
• Khoury JK, Khoury NC, Schaefer D, Chitnis A, Hassen GW. A tick-acquired red meat allergy. Am J Emerg Med. 2018;36(2):341.e1–341.e3. doi:10.1016/j.ajem.2017.10.044
   PubMed Web of Science ®Google Scholar
• Brzozowska M, Mokrzycka N, Porębski G. Alpha-gal syndrome: the first report in Poland. Cent Eur J Immunol. 2021;46(3):398–400. doi:10.5114/ceji.2021.108766
   PubMed Web of Science ®Google Scholar
• Anemüller W, Mohr M, Brans R, Homann A, Jappe U. Alpha-Gal-assoziierte verzögerteAnaphylaxie gegen rotes Fleischals Berufskrankheit. Hautarzt. 2018;69(10):848–852. doi:10.1007/s00105-018-4224-4
   PubMed Web of Science ®Google Scholar
• Ghahramani GK, Temprano J. Tick bite-related meat allergy as a cause of chronic urticaria, angioedema, and anaphylaxis in endemic areas. Int J Dermatol. 2015;54(2):e64–e65. doi:10.1111/ijd.12672
   PubMed Web of Science ®Google Scholar
• Wen L, Zhou J, Yin J, et al. Delayed anaphylaxis to red meat associated with specific IgE antibodies to galactose. Allergy Asthma Immunol Res. 2014;7(1):92–94. doi:10.4168/aair.2015.7.1.92
   PubMed Web of Science ®Google Scholar
• Zhang B, Hauk M, Clyne J. Alpha-gal antibody due to Lone Star tick bite, a unique case of allergic reaction. IDCases. 2020;22:e00908. doi:10.1016/j.idcr.2020.e00908
   PubMed Web of Science ®Google Scholar
• Saleem M, Nilsson C. A pediatric case of tick-bite–Induced meat allergy and recall urticaria. Clin Case Rep. 2021;9(9):1–4. doi:10.1002/ccr3.4773
   Web of Science ®Google Scholar
• Guillier A, Fauconneau A, de Barruel F, Guez S, Doutre MS. Allergic hypersensitivity to red meat induced by tick bites: a French case report. Eur J Dermatol. 2015;25(3):275–276. doi:10.1684/ejd.2015.2533
   Web of Science ®Google Scholar
• Brenner DM, Lacy BE. Antispasmodics for chronic abdominal pain: analysis of North American treatment options. Am J Gastroenterol. 2021;116(8):1587–1600. doi:10.14309/ajg.0000000000001266
   PubMed Web of Science ®Google Scholar
• Bircher AJ, Hofmeier KS, Link S, Heijnen I. Food allergy to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal): four case reports and a review. Eur J Dermatol. 2017;27(1):3–9. doi:10.1684/ejd.2016.2908
   PubMed Web of Science ®Google Scholar
• Emmanuel A, Quigley EMM, Simrén M, et al. Factors affecting satisfaction with treatment in European women with chronic constipation: an internet survey. United Eur Gastroenterol J. 2013;1(5):375–384. doi:10.1177/2050640613494200
   PubMed Web of Science ®Google Scholar
• Galili U. Significance of the evolutionary α1,3-Galactosyltransferase (GGTA1) gene inactivation in preventing extinction of apes and old world monkeys. J Mol Evol. 2015;80(1):1–9. doi:10.1007/s00239-014-9652-x
   PubMed Web of Science ®Google Scholar
• Contreras M, Pacheco I, Alberdi P, et al. Allergic reactions and immunity in response to tick salivary biogenic substances and red meat consumption in the Zebrafish Model. Front Cell Infect Microbiol. 2020;10(3). doi:10.3389/fcimb.2020.00078
   PubMed Web of Science ®Google Scholar
• Pacheco I, Contreras M, Villar M, et al. Vaccination with alpha-gal protects against mycobacterial infection in the zebrafish model of tuberculosis. Vaccines. 2020;8(2):195. doi:10.3390/vaccines8020195
   Web of Science ®Google Scholar
• Bryda EC. The mighty mouse: the impact of rodents on advances in biomedical research. Mo Med. 2013;110(3):207–211.
   PubMedGoogle Scholar
• Fujiwara S. Humanized mice: a brief overview on their diverse applications in biomedical research. J Cell Physiol. 2018;233(4):2889–2901. doi:10.1002/jcp.26022
   PubMed Web of Science ®Google Scholar
• Koike C, Fung JJ, Geller DA, et al. Molecular basis of evolutionary loss of the α1,3-Galactosyltransferase gene in higher primates. J Biol Chem. 2002;277(12):10114–10120. doi:10.1074/jbc.M110527200
   PubMed Web of Science ®Google Scholar
• Dai Y, Vaught TD, Boone J, et al. Targeted disruption of the α1,3-galactosyltransferase gene in cloned pigs. Nat Biotechnol. 2002;20(3):251–255. doi:10.1038/nbt0302-251
   PubMed Web of Science ®Google Scholar
• Tearle RG, Tange MJ, Zannettino ZL, et al. The alpha-1,3-galactosyltransferase knockout mouse. Implications for xenotransplantation. Transplantation. 1996;61(1):13–19. doi:10.1097/00007890-199601150-00004
   PubMed Web of Science ®Google Scholar
• Bryant CD. The blessings and curses of C57BL/6 substrains in mouse genetic studies. Ann N Y Acad Sci. 2011;1245(1):31–33. doi:10.1111/j.1749-6632.2011.06325.x
   PubMed Web of Science ®Google Scholar
• Choudhary SK, Karim S, Iweala OI, et al. Tick salivary gland extract induces alpha-gal syndrome in alpha-gal deficient mice. Immun Inflamm Dis. 2021;9(3):984–990. doi:10.1002/iid3.457
   PubMed Web of Science ®Google Scholar
• Araujo RN, Franco PF, Rodrigues H, et al. Amblyomma sculptum tick saliva: α-Gal identification, antibody response and possible association with red meat allergy in Brazil. Int J Parasitol. 2016;46(3):213–220. doi:10.1016/j.ijpara.2015.12.005
   PubMed Web of Science ®Google Scholar
• Ayala EV, Rodrigues Da Cunha G, Azevedo MA, et al. C57BL/6 α-1,3-Galactosyltransferase knockout mouse as an animal model for experimental Chagas disease. ACS Infect Dis. 2020;6(7):1807–1815. doi:10.1021/acsinfecdis.0c00061
   PubMed Web of Science ®Google Scholar
• Chandrasekhar JL, Cox KM, Loo WM, Qiao H, Tung KS, Erickson LD. Cutaneous exposure to clinically relevant Lone Star ticks promotes IgE production and hypersensitivity through CD4 + T cell– and MyD88-dependent pathways in mice. J Immunol. 2019;203(4):813–824. doi:10.4049/jimmunol.1801156
   PubMed Web of Science ®Google Scholar
• Unal D, Coskun R, Demir S, Gelincik A, Colakoglu B, Buyukozturk S. Successful beef desensitization in 2 adult patients with a delayed-type reaction to red meat. J Allergy Clin Immunol Pract. 2017;5(2):502–503. doi:10.1016/j.jaip.2016.12.008
   PubMed Web of Science ®Google Scholar
• Michelet M, Balbino B, Guilleminault L, Reber LL. IgE in the pathophysiology and therapy of food allergy. Eur J Immunol. 2021;51(3):531–543. doi:10.1002/eji.202048833
   PubMed Web of Science ®Google Scholar
• Yucel E, Sipahi Cimen S, Varol S, Suleyman A, Ozdemir C, Tamay ZU. Red meat desensitization in a child with delayed anaphylaxis due to alpha-Gal allergy. Pediatr Allergy Immunol. 2019;30(7):771–773. doi:10.1111/pai.13092
   PubMed Web of Science ®Google Scholar
• Zhubi-Bakija F, Bajraktari G, Bytyçi I, et al. The impact of type of dietary protein, animal versus vegetable, in modifying cardiometabolic risk factors: a position paper from the International Lipid Expert Panel (ILEP). Clin Nutr. 2021;40(1):255–276. doi:10.1016/j.clnu.2020.05.017
   PubMed Web of Science ®Google Scholar
• Abenavoli L, Boccuto L, Federico A, et al. Diet and non-alcoholic fatty liver disease: the Mediterranean way. Int J Environ Res Public Health. 2019;16(17):3011. doi:10.3390/ijerph16173011
   PubMed Web of Science ®Google Scholar
• Badina L, Burlo F, Belluzzi B, Babich S, Berti I, Barbi E. Life-threatening anaphylaxis in children with cow’s milk allergy during oral immunotherapy and after treatment failure. Immun Inflamm Dis. 2022;10(2):e607. doi:10.1002/iid3.607
   PubMed Web of Science ®Google Scholar
• Guilleminault L, Michelet M, Reber LL. Combining Anti-IgE monoclonal antibodies and oral immunotherapy for the treatment of food allergy. Clin Rev Allergy Immunol. 2022;62(1):216–231. doi:10.1007/s12016-021-08902-0
   PubMed Web of Science ®Google Scholar
• Ramesh M, Karagic M. New modalities of allergen immunotherapy. Human Vaccin Immunother. 2018;14(12):2848–2863. doi:10.1080/21645515.2018.1502126
   PubMed Web of Science ®Google Scholar
• Long A, Borro M, Sampath V, Chinthrajah RS. New developments in non-allergen-specific therapy for the treatment of food allergy. Curr Allergy Asthma Rep. 2020;20(1). doi:10.1007/s11882-020-0897-8
   PubMed Web of Science ®Google Scholar
• Chandrasekhar JL, Cox KM, Erickson LD, Cell B. Responses in the development of mammalian meat allergy. Front Immunol. 2020;11(7):1–16. doi:10.3389/fimmu.2020.01532
   PubMed Web of Science ®Google Scholar
• de la Fuente J, Kopáček P, Lew-Tabor A, Maritz-Olivier C. Strategies for new and improved vaccines against ticks and tick-borne diseases. Parasite Immunol. 2016;38(12):754–769. doi:10.1111/pim.12339
   PubMed Web of Science ®Google Scholar
• Hromníková D, Furka D, Furka S, et al. Prevention of tick-borne diseases: challenge to recent medicine. Biologia. 2022;77(3):1533–1554. doi:10.1007/s11756-021-00966-9
   PubMed Web of Science ®Google Scholar
• Narasimhan S, Kurokawa C, DeBlasio M, et al. Acquired tick resistance: the trail is hot. Parasite Immunol. 2021;43(5):e12808. doi:10.1111/pim.12808
   PubMed Web of Science ®Google Scholar
• Karasuyama H, Miyake K, Yoshikawa S. Immunobiology of acquired resistance to ticks. Front Immunol. 2020;11(10):601504. doi:10.3389/fimmu.2020.601504
   PubMed Web of Science ®Google Scholar
• Kuravi KV, Sorrells LT, Nellis JR, et al. Allergic response to medical products in patients with alpha-gal syndrome. J Thorac Cardiovasc Surg. 2021;9(3). doi:10.1016/j.jtcvs.2021.03.100
   Google Scholar