Galactose-α-1,3-galactose (alpha-gal) allergy: first pediatric case in a series of patients in Spain

Main Article Content

Martín-Lázaro J
Núnez-Orjales R
González-Guzmán L.A.
González M.T.
Boquete M.
Carballada F.

Keywords

Alpha-galactosidase, Delayed meat allergy, Anaphylaxis, Cetuximab allergy, Bovine amniotic fluid allergy

Abstract

Introduction and Objectives: Allergy to galactose-1,3-galactose (alpha-gal) is a peculiar form of food allergy generally manifesting as an anaphylactic reaction hours after mammalian meat consumption, due to the presence of specific IgE against this oligosaccharide. In addition, immediate anaphylaxis may develop after exposure to other sources of alpha-gal, such as monoclonal antibody cetuximab, vaccines, plasma expanders or anti-snake venoms. Sensitization to alpha-gal has also been implicated in the rapid degeneration of biological valve implants, and recognized as a cause of occupational disease in cattle raisers. The implication of tick bites in this type of sensitization has been accepted by all the research groups dedicated to this
disease.


Patients and method: The present study describes the clinical and sensitization characteristics of 39 patients diagnosed with alpha-gal allergy in the hospitals of our province (Lugo, Monforte de Lemos and Burela, Spain).


Results: Most patients were middle-age males. Of note, is the fact that the series includes the first pediatric patient-reported in Spain to date. The predominant clinical manifestations were urticaria or delayed anaphylaxis after consumption of mammalian meat. Seventy-four percent of the patients reported having suffered a previous tick bite, and the clinical presentation of anaphylaxis was significantly more prevalent in those with a persistent local reaction following the bite than in those with no such reaction (p = 0.032).


Conclusions: A review is also made of the disorder which, due to its variable clinical expression, is referred to as alpha-gal syndrome. The study concludes that a diagnosis of alpha-gal allergy should be considered in patients with urticaria-anaphylaxis of uncertain origin or manifesting after the administration of vaccines or products of bovine/porcine origin.

Abstract 31 | PDF Downloads 42

References

1. Macher BA, Galili U. The Galalpha1,3 Galbeta1,4GlcNAc-R (alpha-Gal) epitope: a carbohydrate of unique evolution and clinical relevance. Biochim Biophys Acta. 2008;1780(2):75-88.

2. Van Nunen SA, O’Connor KS, Clarke LR, Boyle RX, Fernando SL. An association between tick bite reactions and red meat allergy in humans. Med J Aust. 2009;190(9):510-1.

3. Adédoyin J, Grönlund H, Oman H, Johansson SG, van Hage M. Cat IgA, representative of new carbohydrate cross-reactive allergens. J Allergy Clin Immunol. 2007;119(3):640-5.

4. O’Neil BH, Allen R, Spigel DR, Stinchcombe TE, Moore DT, Berlin JD, et al. High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol. 2007;25(24):3644-8.

5. Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose alpha-1,3 galactose. N Engl J Med. 2008;358(11):1109-17.

6. Commins SP, Satinover SM, Hosen J, Mozena J, Borish L, Lewis BD, et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J Allergy Clin Immunol. 2009;123(2):426-33.

7. Commins SP, James HR, Kelly LA, Pochan SL, Workman LJ, Perzanowski MS, et al. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-1,3-galactose. J Allergy Clin Immunol. 2011;127(5):1286-93.

8. Nunez ˜ R, Carballada F, Gonzalez-Quintela A, Gomez-Rial J, Boquete M, Vidal C. Delayed mammalian meat-induced anaphylaxis due to galactose-1,3-galactose in 5 European patients. J Allergy Clin Immunol. 2011;128(5):1122-4.

9. Caponetto P, Fischer J, Biedermann T. Gelatin-containing sweets can elicit anaphylaxis in a patient with sensitization to galactose-1,3 galactose. J Allergy Clin Immunol Pract. 2013;1(3):302-3.

10. Mullins RJ, James H, Platts-Mills TA, Commins S. Relationship between red meat allergy and sensitization to gelatin and galactose-1,3 galactose. J Allergy Clin Immunol. 2012;129(5):1334-42.

11. Vidal C, Méndez-Brea P, López-Freire S, González-Vidal T. Vaginal capsules: an unsuspected probable source of exposure to alpha-gal. J Investig Allergol Clin Immunol. 2016;26(6):388-9.

12. Swiontek K, Morisset M, Codreanu-Morel F, Fischer J, Mehlich J, Darsow U, et al. Drugs of porcine origin - a risk for patients with -Gal syndrome? J Allergy Clin Immunol Pract. 2018, pii: S2213-2198(18)30825-0. doi: 10.1016/j.jaip.2018.12.005. [Epub ahead of print] PubMed PMID: 30557715.

13. Naso F, Gandaglia A, Bottio T, Tarzia V, Nottle MB, d’Apice AJ, et al. First quantification of alpha-Gal epitope in current glutaraldehyde fixed heart valve bioprostheses. Xenotransplantation. 2013;20(4):252-61.

14. Mozzicato SM, Tripathi A, Posthumus JB, Platts-Mills TAE, Commins SP. Porcine or bovine valve replacement in 3 patients with IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose. J Allergy Clin Immunol Pract. 2014;2:637-8.

15. Fischer J, Eberlein B, Hilger C, Eyer F, Eyerich S, Ollert M, et al. Alpha-gal is a possible target of IgE-mediated reactivity to antivenom. Allergy. 2017;72(5):764-71.

16. Rizer J, Brill K, Charlton N, King J. Acute hypersensitivity reaction to Crotalidae polyvalent immune Fab (CroFab) as initial presentation of galactose-1,3-galactose (-gal) allergy. Clin Toxicol (Phila). 2017;55(7):668-9.

17. Nunez-Orjales ˜ R, Martin-Lazaro J, Lopez-Freire S, Galan-Nieto A, Lombardero-Vega M, Carballada-Gonzalez F. Bovine amniotic fluid: a new and occupational source of galactose-1,3- galactose. J Investig Allergol Clin Immunol. 2017;27(5):313-4.

18. Kennedy JL, Stallings AP, Platts-Mills TA, Oliveira WM, Workman L, James HR, et al. Galactose--1,3-galactose and delayed anaphylaxis, angioedema, and urticaria in children. Pediatrics. 2013;131(5):e1545-52.

19. Stone CA Jr, Commins SP, Choudhary S, Vethody C, Heavrin JL, Wingerter J, et al. Anaphylaxis after vaccination in a pediatric patient: further implicating alpha-gal allergy. J Allergy Clin Immunol Pract. 2018, pii: S2213-2198(18)30393-3.

20. Stone CA Jr, Hemler JA, Commins SP, Schuyler AJ, Phillipe EJ, Peebles RE Jr, et al. Anaphylaxis after zoster vaccine: implicating alpha-gal allergy as a possible mechanism. J Allergy Clin Immunol. 2017;139(5):1710-3.

21. Brockow K, Garvey LH, Aberer W, Atanaskovic-Markovic M, Barbaud A, Bilo MB, et al. Skin test concentrations for systemically administered drugs - an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy. 2013;68(6):702-12.

22. Commins SP, Platts-Mills TA. Allergenicity of carbohydrates and their role in anaphylactic events. Curr Allergy Asthma Rep. 2010;10(1):29-33.

23. Homann A, Schramm G, Jappe U. Glycans and glycan-specific IgE in clinical and molecular allergology; sensitization, diagnostics, and clinical symptoms. J Allergy Clin Immunol. 2017;140(2):356-68.

24. Gonzalez-Quintela A, Gomez-Rial J, Valcárcel C, Campos J, Sanz ML, Linneberg A, et al. Immunoglobulin-E reactivity to wine glycoproteins in heavy drinkers. Alcohol. 2011;45(2): 113-22.

25. Jappe U, Minge S, Kraft B, Ludwig A, Przybilla B, Walker A, et al. Meat allergy associated with galactosyl-(1,3)-galactose (-Gal)-closing diagnostic gaps by anti-Gal IgE immune profiling. Allergy. 2018;73(1):93-105.

26. Wilson JM, Schuyler AJ, Schroeder N, Platts-MIlls TA. Galactosealpha-1,3-galactose: atypical food allergen or model IgE hypersensitivity? Curr Allergy Asthma Rep. 2017;17(1):8.

27. Apostolovic D, Krstic M, Mihailovic J, Starkhammar M, Cirkovic Velickovic T, Hamsten C, et al. Peptidomics of an in vitro digested -Gal carrying protein revealed IgE-reactive peptides. Sci Rep. 2017;7(1):5201.

28. Pattanaik D, Lieberman P, Lieberman J, Pongdee T, Keene AT. The changing face of anaphylaxis in adults and adolescents. Ann Allergy Asthma Immunol. 2018;121(5):594-7.

29. Wilson JM, Nguyen AT, Schuyler AJ, Commins SP, Taylor AM, Platts-Mills TAE, et al. IgE to the mammalian oligosaccharide galactose-1,3-galactose is associated with increased atheroma volume and plaques with unstable characteristics brief report. Arterioscler Thromb Vasc Biol. 2018;38(7):1665-9.

30. Van Nunen SA. Tick-induced allergies: mammalian meat allergy and tick anaphylaxis. Med J Aust. 2018;208(7):316-21.

31. Araujo RN, Franco PF, Rodrigues H, Santos LCB, McKay CS, Sanhueza CA, et al. Amblyomma sculptum tick saliva: -Gal identification, antibody response and possible association with red meat allergy in Brazil. Int J Parasitol. 2016;46(3):213-20.

32. Hamsten C, Starkhammar M, Tran TA, Johansson M, Bengtsson U, Ahlén G, et al. Identification of galactose-1,3-galactose in the gastrointestinal tract of the tick Ixodes ricinus; possible relationship with red meat allergy. Allergy. 2013;68(4): 549-52.

33. Vázquez L, Panadero R, Dacal V, Pato FJ, López C, Díaz P, et al. Tick infestation (Acari: Ixodidae) in roe deer (Capreolus capreolus) from northwestern Spain: population dynamics and risk stratification. Exp Appl Acarol. 2011;53(4):399-409.

34. Cabezas-Cruz A, Espinosa PJ, Alberdi P, ˇSimo L, Valdés JJ, Mateos-Hernández L, et al. Tick galactosyltransferases are involved in -Gal synthesis and play a role during Anaplasma phagocytophilum infection and Ixodes scapularis tick vector development. Sci Rep. 2018;8(1):14224.

35. Commins SP, Platts-Mills TA. Tick bites and red meat allergy. Curr Opin Allergy Clin Immunol. 2013;13:354-9.

36. Burke G, Wikel SK, Spielman A, Telford SR, McKay K, Krause PJ. Tick-borne Infection Study Group. Hypersensitivity to ticks and Lyme disease risk. Emerg Infect Dis. 2005;11(1):36-41.

37. Venturini M, Lobera T, Sebastian A, Portillo A, Oteo JA. IgE to alfa-tal in forestes. and forest workers from La Rioja, North of Spain. J Investig Allergol Clin Immunol. 2018;28(2): 106-12.

38. Fischer J, Lupberger E, Hebsaker J, Blumenstock G, Aichinger E, Yazdi AS, et al. Prevalence of type I sensitization to alpha-gal in forest service employees and hunters. Allergy. 2017;72(10):1540-7.

39. 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):1061-8.

40. Martínez Arcediano A, Audicana Berasategui MT, Longo Areso N, Ibánez ˜ EF, Balza de Vallejo OV, Velasco Azagra M, et al. Allergy to galactose-alpha-1,3-galactose: clinical features and the diagnostic value of cetuximab. J Investig Allergol Clin Immunol. 2014;24(6):450-2.

41. Cabezas-Cruz A, De la fuente J, Fischer J, Hebsaker J, Lupberger E, Blumensthck G, et al. Prevalence of type I sensitization to alpha-gal in forest service employees and hunters: is the blood type an overlooked risk factor in epidermiological studies of the alfa-gal syndrome? Allergy. 2017;72(12): 2044-7.