Asia Pac Allergy.  2015 Jan;5(1):17-24. 10.5415/apallergy.2015.5.1.17.

Carbohydrates as food allergens

• Soh JY
• Huang CH
• Lee BW

• KMID: 2397063
• DOI: http://doi.org/10.5415/apallergy.2015.5.1.17

Abstract

The literature supports the notion that carbohydrate epitopes, on their own, do not contribute significantly to the induction of allergic reactions. They bind weakly to IgE antibodies and have been termed as cross reactive carbohydrate determinants. These epitopes cause confusion in in vitro IgE testing through nonspecific cross-reactivity. Coincident with the rising trends in food allergy prevalence, there has recently been reports of anaphylaxis induced by carbohydrate epitopes. There are two distinct groups, each with unique characteristics and geographical distribution. Anaphylaxis and acute allergic reactions related to the carbohydrate galactose-α-1,3-galactose (α-Gal) epitope that are present in the monoclonal antibody, cetuximab and red meat have been described in the United States and Europe populations where tick bites have been found to be the primary sensitizer. Another carbohydrate inducing anaphylaxis is galacto-oligosaccharides in commercial milk formula which has been described in the several Asian populations including Singapore. The latter is unique in that the allergen is a pure carbohydrate. We summarize the current literature on carbohydrate-induced food allergy, and evaluate the two new groups of carbohydrate allergy that have defied previous findings on carbohydrates and their role.

Keyword

Carbohydrates; Cross reactions; Oligosaccharides; Food hypersensitivity; Anaphylaxis

MeSH Terms

Allergens*
Anaphylaxis
Antibodies
Asian Continental Ancestry Group
Carbohydrates*
Cetuximab
Cross Reactions
Epitopes
Europe
Food Hypersensitivity
Humans
Hypersensitivity
Immunoglobulin E
In Vitro Techniques
Milk
Oligosaccharides
Prevalence
Red Meat
Singapore
Tick Bites
United States
Allergens
Antibodies
Carbohydrates
Cetuximab
Epitopes
Immunoglobulin E
Oligosaccharides

Reference

1. Fotisch K, Vieths S. N- and O-linked oligosaccharides of allergenic glycoproteins. Glycoconj J. 2001; 18:373–390.

2. Aalberse RC, Koshte V, Clemens JG. Immunoglobulin E antibodies that crossreact with vegetable foods, pollen, and Hymenoptera venom. J Allergy Clin Immunol. 1981; 68:356–364.

3. Jappe U, Raulf-Heimsoth M, Hoffmann M, Burow G, Hubsch-Muller C, Enk A. In vitro hymenoptera venom allergy diagnosis: improved by screening for cross-reactive carbohydrate determinants and reciprocal inhibition. Allergy. 2006; 61:1220–1229.

4. van der Veen MJ, van Ree R, Aalberse RC, Akkerdaas J, Koppelman SJ, Jansen HM, van der Zee JS. Poor biologic activity of cross-reactive IgE directed to carbohydrate determinants of glycoproteins. J Allergy Clin Immunol. 1997; 100:327–334.

5. Mahler V, Gutgesell C, Valenta R, Fuchs T. Natural rubber latex and hymenoptera venoms share ImmunoglobinE-epitopes accounting for cross-reactive carbohydrate determinants. Clin Exp Allergy. 2006; 36:1446–1456.

6. Mari A, Ooievaar-de Heer P, Scala E, Giani M, Pirrotta L, Zuidmeer L, Bethell D, van Ree R. Evaluation by double-blind placebo-controlled oral challenge of the clinical relevance of IgE antibodies against plant glycans. Allergy. 2008; 63:891–896.

7. Lauer I, Foetisch K, Kolarich D, Ballmer-Weber BK, Conti A, Altmann F, Vieths S, Scheurer S. Hazelnut (Corylus avellana) vicilin Cor a 11: molecular characterization of a glycoprotein and its allergenic activity. Biochem J. 2004; 383(Pt 2):327–334.

8. Garrido-Arandia M, Murua-Garcia A, Palacin A, Tordesillas L, Gomez-Casado C, Blanca-Lopez N, Ramos T, Canto G, Blanco C, Cuesta-Herranz J, Sanchez-Monge R, Pacios LF, Díaz Perales A. The role of N-glycosylation in kiwi allergy. Food Sci Nutr. 2014; 2:260–271.

9. Mari A. IgE to cross-reactive carbohydrate determinants: analysis of the distribution and appraisal of the in vivo and in vitro reactivity. Int Arch Allergy Immunol. 2002; 129:286–295.

10. Kochuyt AM, Van Hoeyveld EM, Stevens EA. Prevalence and clinical relevance of specific immunoglobulin E to pollen caused by stinginduced specific immunoglobulin E to cross-reacting carbohydrate determinants in Hymenoptera venoms. Clin Exp Allergy. 2005; 35:441–447.

11. Linneberg A, Fenger RV, Husemoen LL, Vidal C, Vizcaino L, Gonzalez-Quintela A. Immunoglobulin E sensitization to cross-reactive carbohydrate determinants: epidemiological study of clinical relevance and role of alcohol consumption. Int Arch Allergy Immunol. 2010; 153:86–94.

12. Gonzalez-Quintela A, Garrido M, Gude F, Campos J, Linneberg A, Lojo S, Vidal C. Sensitization to cross-reactive carbohydrate determinants in relation to alcohol consumption. Clin Exp Allergy. 2008; 38:152–160.

13. Coutinho V, Vidal C, Garrido M, Gude F, Lojo S, Linneberg A, Gonzalez-Quintela A. Interference of cross-reactive carbohydrates in the determination of specific IgE in alcohol drinkers and strategies to minimize it: the example of latex. Ann Allergy Asthma Immunol. 2008; 101:394–401.

14. Carballada FJ, Gonzalez-Quintela A, Nunez-Orjales R, Vizcaino L, Boquete M. Double (honeybee and wasp) immunoglobulin E reactivity in patients allergic to Hymenoptera venom: the role of cross-reactive carbohydrates and alcohol consumption. J Investig Allergol Clin Immunol. 2010; 20:484–489.

15. Gonzalez-Quintela A, Gomez-Rial J, Valcarcel C, Campos J, Sanz ML, Linneberg A, Gude F, Vidal C. Immunoglobulin-E reactivity to wine glycoproteins in heavy drinkers. Alcohol. 2011; 45:113–122.

16. Ebo DG, Hagendorens MM, Bridts CH, De Clerck LS, Stevens WJ. Sensitization to cross-reactive carbohydrate determinants and the ubiquitous protein profilin: mimickers of allergy. Clin Exp Allergy. 2004; 34:137–144.

17. Tretter V, Altmann F, Kubelka V, Marz L, Becker WM. Fucose alpha 1,3-linked to the core region of glycoprotein N-glycans creates an important epitope for IgE from honeybee venom allergic individuals. Int Arch Allergy Immunol. 1993; 102:259–266.

18. Muller UR, Johansen N, Petersen AB, Fromberg-Nielsen J, Haeberli G. Hymenoptera venom allergy: analysis of double positivity to honey bee and Vespula venom by estimation of IgE antibodies to speciesspecific major allergens Api m1 and Ves v5. Allergy. 2009; 64:543–548.

19. Holzweber F, Svehla E, Fellner W, Dalik T, Stubler S, Hemmer W, Altmann F. Inhibition of IgE binding to cross-reactive carbohydrate determinants enhances diagnostic selectivity. Allergy. 2013; 68:1269–1277.

20. Amoah AS, Obeng BB, Larbi IA, Versteeg SA, Aryeetey Y, Akkerdaas JH, Zuidmeer L, Lidholm J, Fernandez-Rivas M, Hartgers FC, Boakye DA, van Ree R, Yazdanbakhsh M. Peanut-specific IgE antibodies in asymptomatic Ghanaian children possibly caused by carbohydrate determinant cross-reactivity. J Allergy Clin Immunol. 2013; 132:639–647.

21. Altmann F. The role of protein glycosylation in allergy. Int Arch Allergy Immunol. 2007; 142:99–115.

22. Borres MP, Ebisawa M, Eigenmann PA. Use of allergen components begins a new era in pediatric allergology. Pediatr Allergy Immunol. 2011; 22:454–461.

23. Suratannon N, Ngamphaiboon J, Wongpiyabovorn J, Puripokai P, Chatchatee P. Component-resolved diagnostics for the evaluation of peanut allergy in a low-prevalence area. Pediatr Allergy Immunol. 2013; 24:665–670.

24. Masthoff LJ, Mattsson L, Zuidmeer-Jongejan L, Lidholm J, Andersson K, Akkerdaas JH, Versteeg SA, Garino C, Meijer Y, Kentie P, Versluis A, den Hartog Jager CF, Bruijnzeel-Koomen CA, Knulst AC, van Ree R, van Hoffen E, Pasmans SG. Sensitization to Cor a 9 and Cor a 14 is highly specific for a hazelnut allergy with objective symptoms in Dutch children and adults. J Allergy Clin Immunol. 2013; 132:393–399.

25. Villalta D, Conte M, Asero R, Da Re M, Stella S, Martelli P. Isolated IgE reactivity to native walnut vicilin-like protein (nJug r 2) on ISAC™ microarray is due to cross-reactive carbohydrate epitopes. Clin Chem Lab Med. 2013; 51:1991–1995.

26. Luengo O, Cardona V. Component resolved diagnosis: when should it be used? Clin Transl Allergy. 2014; 4:28.

27. Vereda A, van Hage M, Ahlstedt S, Ibanez MD, Cuesta-Herranz J, van Odijk J, Wickman M, Sampson HA. Peanut allergy: Clinical and immunologic differences among patients from 3 different geographic regions. J Allergy Clin Immunol. 2011; 127:603–607.

28. Aalberse RC, van Ree R. Crossreactive carbohydrate determinants. Clin Rev Allergy Immunol. 1997; 15:375–387.

29. Leonard R, Petersen BO, Himly M, Kaar W, Wopfner N, Kolarich D, van Ree R, Ebner C, Duus JO, Ferreira F, Altmann F. Two novel types of O-glycans on the mugwort pollen allergen Art v 1 and their role in antibody binding. J Biol Chem. 2005; 280:7932–7940.

30. Kaulfurst-Soboll H, Mertens M, Brehler R, von Schaewen A. Reduction of cross-reactive carbohydrate determinants in plant foodstuff: elucidation of clinical relevance and implications for allergy diagnosis. PLoS One. 2011; 6:e17800.

31. Joshi AA, Peczuh MW, Kumar CV, Rusling JF. Ultrasensitive carbohydrate-peptide SPR imaging microarray for diagnosing IgE mediated peanut allergy. Analyst. 2014; 139:5728–5733.

32. Kathan RH, Weeks DI. Structure studies of collocalia mucoid. I. Carbohydrate and amino acid composition. Arch Biochem Biophys. 1969; 134:572–576.

33. Goh DL, Lau YN, Chew FT, Shek LP, Lee BW. Pattern of food-induced anaphylaxis in children of an Asian community. Allergy. 1999; 54:84–86.

34. Goh DL, Chew FT, Chua KY, Chay OM, Lee BW. Edible "bird's nest"-induced anaphylaxis: An under-recognized entity? J Pediatr. 2000; 137:277–279.

35. Goh DL, Chua KY, Chew FT, Liang RC, Seow TK, Ou KL, Yi FC, Lee BW. Immunochemical characterization of edible bird's nest allergens. J Allergy Clin Immunol. 2001; 107:1082–1087.

36. Arai T, Takaya T, Ito Y, Hayakawa K, Toshima S, Shibuya C, Nomura M, Yoshimi N, Shibayama M, Yasuda Y. Bronchial asthma induced by rice. Intern Med. 1998; 37:98–101.

37. Wuthrich B, Scheitlin T, Ballmer-Weber B. Isolated allergy to rice. Allergy. 2002; 57:263–264.

38. Orhan F, Sekerel BE. A case of isolated rice allergy. Allergy. 2003; 58:456–457.

39. Monzón S, Lombardero M, Perez-Camo I, Saenz D, Lasanta J. Allergic rhinoconjunctivitis after ingestion of boiled rice. J Investig Allergol Clin Immunol. 2008; 18:487–488.

40. Trcka J, Schad SG, Scheurer S, Conti A, Vieths S, Gross G, Trautmann A. Rice-induced anaphylaxis: IgE-mediated allergy against a 56-kDa glycoprotein. Int Arch Allergy Immunol. 2012; 158:9–17.

41. Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M, Murphy BA, Satinover SM, Hosen J, Mauro D, Slebos RJ, Zhou Q, Gold D, Hatley T, Hicklin DJ, Platts-Mills TA. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med. 2008; 358:1109–1117.

42. Commins SP, Satinover SM, Hosen J, Mozena J, Borish L, Lewis BD, Woodfolk JA, Platts-Mills TA. 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; 123:426–433.

43. Van Nunen SA, O'Connor KS, Fernando SL, Clarke LR, Boyle RX. An association between Ixodesholocyclus tick bite reactions and red meat allergy [abstract]. Int Med J. 2007; 39:Suppl 5. A132.

44. 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; 190:510–511.

45. Commins SP, James HR, Kelly LA, Pochan SL, Workman LJ, Perzanowski MS, Kocan KM, Fahy JV, Nganga LW, Ronmark E, Cooper PJ, Platts-Mills TA. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose. J Allergy Clin Immunol. 2011; 127:1286–1293.

46. Hamsten C, Tran TA, Starkhammar M, Brauner A, Commins SP, Platts-Mills TA, van Hage M. Red meat allergy in Sweden: association with tick sensitization and B-negative blood groups. J Allergy Clin Immunol. 2013; 132:1431–1434.

47. Morisset M, Richard C, Astier C, Jacquenet S, Croizier A, Beaudouin E, Cordebar V, Morel-Codreanu F, Petit N, Moneret-Vautrin DA, Kanny G. Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose. Allergy. 2012; 67:699–704.

48. Tripathi A, Commins SP, Heymann PW, Platts-Mills TA. Delayed anaphylaxis to red meat masquerading as idiopathic anaphylaxis. J Allergy Clin Immunol Pract. 2014; 2:259–265.

49. Kennedy JL, Stallings AP, Platts-Mills TA, Oliveira WM, Workman L, James HR, Tripathi A, Lane CJ, Matos L, Heymann PW, Commins SP. Galactose-α-1,3-galactose and delayed anaphylaxis, angioedema, and urticaria in children. Pediatrics. 2013; 131:e1545–e1552.

50. Saleh H, Embry S, Nauli A, Atyia S, Krishnaswamy G. Anaphylactic reactions to oligosaccharides in red meat: a syndrome in evolution. Clin Mol Allergy. 2012; 10:5.

51. Nunez R, Carballada F, Gonzalez-Quintela A, Gomez-Rial J, Boquete M, Vidal C. Delayed mammalian meat-induced anaphylaxis due to galactose-α-1,3-galactose in 5 European patients. J Allergy Clin Immunol. 2011; 128:1122–1124.e1.

52. Commins SP, James HR, Stevens W, Pochan SL, Land MH, King C, Mozzicato S, Platts-Mills TA. Delayed clinical and ex vivo response to mammalian meat in patients with IgE to galactose-alpha-1,3-galactose. J Allergy Clin Immunol. 2014; 134:108–115.

53. Ohta M, Matsuura F, Kobayashi Y, Shigeta S, Ono K, Oka S. Further characterization of allergenically active oligosaccharitols isolated from a sea squirt H-antigen. Arch Biochem Biophys. 1991; 290:474–483.

54. Ohta M, Shigeta S, Ono K, Takao T, Shimonishi Y, Oka S. Sugar sequences of allergenically active oligosaccharide alcohols isolated from a large-molecular-size sea squirt antigen termed H-antigen. Arch Biochem Biophys. 1989; 275:151–165.

55. Jyo T, Kuwabara M, Kodommari Y, Tanemori N, Asaoku Y, Katsutani T, Otsuka T, Tsuboi S, Ono K, Shigeta S. Cases of immediate-type allergy in oyster shuckers due to galacto-oligosaccharide. J Hiroshima Med Assoc. 1993; 25:19–26.

56. Matsumoto K, Kobayashi Y, Ueyama S, Watanabe T, Tanaka R, Kan T, Kuroda A, Sumihara Y. Oligosaccharides: production, properties, and applications. In : Nakakuki T, editor. Japanese technology reviews, section E: biotechnology. . New York: Gordon and Breach Science;1993. p. 90–106.

57. Deguchi Y, Matsumoto K, Ito M, Watanuki M. Effects of β1-4 galactooligosaccharides administration on defecation of healthy volunteers with constipation tendency. Jpn J Nutr. 1997; 55:13–22.

58. Wijnands MV, Appel MJ, Hollanders VM, Woutersen RA. A comparison of the effects of dietary cellulose and fermentable galacto-oligosaccharide, in a rat model of colorectal carcinogenesis: fermentable fibre confers greater protection than non-fermentable fibre in both high and low fat backgrounds. Carcinogenesis. 1999; 20:651–656.

59. Vo TH, Le NH, Patel MS, Phan LT, Tran Minh NN. Acute allergic reactions in Vietnamese children after drinking a new milk product. Foodborne Pathog Dis. 2012; 9:156–159.

60. Chiang WC, Huang CH, Llanora GV, Gerez I, Goh SH, Shek LP, Nauta AJ, Van Doorn WA, Bindels J, Ulfman LH, Knipping K, Delsing DJ, Knol EF, Lee BW. Anaphylaxis to cow's milk formula containing short-chain galacto-oligosaccharide. J Allergy Clin Immunol. 2012; 130:1361–1367.

61. Kaneko K, Watanabe Y, Kimura K, Matsumoto K, Mizobuchi T, Onoue M. Development of hypoallergenic galacto-oligosaccharides on the basis of allergen analysis. Biosci Biotechnol Biochem. 2014; 78:100–108.

62. Yanahira S, Kobayashi T, Suguri T, Nakakoshi M, Miura S, Ishikawa H, Nakajima I. Formation of oligosaccharides from lactose by Bacillus circulans beta-galactosidase. Biosci Biotechnol Biochem. 1995; 59:1021–1026.