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Cross-Reactive Carbohydrate Determinants: Diagnostic and Clinical Relevance

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Molecular Allergy Diagnostics
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Abstract

Many allergens are glycoproteins. However, the IgE reactivity of the relevant glycan moiety rarely seems to be of clinical relevance. This is not the case for galactose-α-1,3-galactose (α-gal), a carbohydrate epitope present in the tissue of non-primate mammals, except the New World monkeys, and prosimians. IgE antibodies toward α-gal (anti-α-gal IgE) are associated not only with severe allergic reactions but also with delayed-type anaphylaxis. Allergologically relevant carbohydrate determinants, therefore, differ considerably in respect to structure, occurrence, association with clinical symptoms, and degree of severity.

This contribution is based on a publication by the authors that appeared in the Allergo Journal in 2013 (Jappe U, Petersen A, Raulf-Heimsoth M: Allergische Soforttypreaktionen und kreuzreaktive Kohlenhydratepitope (CCD). Allergo J 2013; 22: 25–32) and which has now been updated, expanded, and translated into English as a chapter for this book.

We are grateful to Dr. Ozan Angün of Lübeck University’s Department of Dermatology, Dr. Arne Homann, Div. of Clinical and Molecular Allergology, Research Center Borstel, for the graphics used in Fig. 6.1, and Professor Arnd Petersen of Research Center Borstel for preparing Fig. 6.2 and reviewing the manuscript.

The authors gratefully thank Dr. Steve Love, PhD, Laguna Niguel, CA, USA, for reading the manuscript, helpful suggestions, and editorial assistance with the English translation.

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Abbreviations

α-gal:

Galactose-α-1,3-galactose

CAP:

Capsulated hydrophilic carrier polymer

CCD:

Cross-reactive carbohydrate determinant

Fab:

Fragment antigen binding

FEIA:

Fluorescent enzyme immunoassay

HSA:

Human serum albumin

HRP:

Horseradish peroxidase

MBP:

Maltose-binding protein

MMX:

Man α-1,6 (Man α-1,3) (Xyl β-1,2) Man β-1,4 GlcNAc β-1,4 GlcNAc

α-D-mannosyl-(1->6)-[α-D-mannosyl-(1->3)]-[β-D-xylosyl-(1->2)]-β-D-mannosyl-(1->4)-N-acetyl-β-D-glucosaminyl-(1->4)-N-acetyl-D-glucosamine

MMXF3:

Man α-1,6 (Man α-1,3)-(Xyl β-1,2) Man β-1,4 GlcNAc β-1,4 (Fuc α-1,3) GlcNAc

α-D-mannosyl-(1->6)-[α-D-mannosyl-(1->3)]-[β-D-xylosyl-(1->2)]-β-D-mannosyl-(1->4)-N-acetyl-β-D-glucosaminyl-(1->4)]-N-acetyl-D-glucosamine

MUXF:

Man α-1,6 (Xyl β-1,2) Man β-1,4 GlcNAc β-1,4 (Fuc α-1,3) GlcNAc

α-D-mannosyl-(1->6)-[β-D-xylosyl-(1->2)]-β-D-mannosyl-(1->4)-N-acetyl-β-D-glucosaminyl-(1->4)]-[α-L-fucosyl-(1->3)]-N-acetyl-D-glucosamine

MMF3F6:

Man α-1,6 (Man α-1,3) Man β-1,4 GlcNAc β-1,4 (Fuc α-1,3) (Fuc α-1,6) GlcNAc

α-D-mannosyl-(1->6)-[α-D-mannosyl-(1->3)]-β-D-mannosyl-(1->4)-N-acetyl-β-D-glucosaminyl-(1->4)]-[α-L-fucosyl-(1->3)]-[α-L-fucosyl-(1->6)]-N-acetyl-D-glucosamine

References

  • Aalberse RC, Koshte V, Clemens JG. Immunoglobulin E antibodies that crossreact with vegetable foods, pollen, and hymenoptera venom. J Allergy Clin Immunol. 1981;68:356–64.

    Article  CAS  PubMed  Google Scholar 

  • Aberer W, Holzweber F, Hemmer W, Koch L, Bokanovic S, Fellner W, Altmann F. Inhibition kreuzreaktiver Kohlenhydratdeterminanten (CCDs) erhöht die Treffsicherheit der In-vitro-Allergiediagnostik. Allergologie. 2014;37:45–53.

    Article  Google Scholar 

  • Adedoyin J, Grönlund H, Öman H, Johansson SGO, van Hage M. Cat IgA, representative of new carbohydrate cross-reactive allergens. J Allergy Clin Immunol. 2007;119:640–5.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Altmann F. Basophil activation test is better but not good enough for the diagnosis of hymenoptera venom allergy: the problem of cross-reactive carbohydrate determinants. Clin Exp Allergy. 2010;40:1290–2.

    Article  CAS  PubMed  Google Scholar 

  • Andrade MC, Menezes JS, Cassali GD, Martins-Filho OA, Cara DC, Faria AM. Alcohol-induced gastritis prevents oral tolerance induction in mice. Clin Exp Immunol. 2006;146:312–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Armentia A, Pineda F, Fernández S. Wine-induced anaphylaxis and sensitization to hymenoptera venom. N Engl J Med. 2007;357:719–20.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Carballada FJ, Gonzalez-Quintela A, Nuñez R, Vidal C, Boquete M. Low prevalence of IgE to cross-reactive carbohydrate determinants in bee-keepers. J Allergy Clin Immunol. 2011;128:1350–2.

    Article  CAS  PubMed  Google Scholar 

  • 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;358:1109–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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;123:426–33.

    Article  CAS  PubMed  Google Scholar 

  • Commins SP, Platts-Mills TA. Delayed anaphylaxis to red meat in patients with IgE specific for galactose alpha-1,3-galactose (α-GAL). Curr Allergy Asthma Rep. 2013;13:72–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Di Gennaro C, Biggi A, Barilli AL, Fasoli E, Carra N, Novarini A, Delsignore R, Montanari A. Endothelial dysfunction and cardiovascular risk profile in long-term withdrawing alcoholics. J Hypertens. 2007;25:367–73.

    Article  PubMed  Google Scholar 

  • Garcia-Casado G, Sanchez-Monge R, Chrispeels MJ, Armentia A, Salcedo G, Gomez L. Role of complex asparagine-linked glycans in the allergenicity of plant glycoproteins. Glycobiology. 1996;6:471–7.

    Article  CAS  PubMed  Google Scholar 

  • 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;38:152–60.

    CAS  PubMed  Google Scholar 

  • González-Quintela A, Garrido M, Gude F, Campos J, Lojo S, Linneberg A, Vidal C. Discordant positive results of multiallergen immunoglobulin E tests in relation to crossreactive carbohydrate determinants and alcohol consumption. J Investig Allergol Clin Immunol. 2009;19:70–1.

    PubMed  Google Scholar 

  • Gonzalez-Quintela A, Valcarcel C, Campos J, Alonso M, Sanz ML, Vidal C. Biologic activity of cross-reactive carbohydrate determinants in heavy drinkers. Clin Exp Allergy. 2011;41:759–61.

    Article  CAS  PubMed  Google Scholar 

  • Hamsten C, Starkhammar M, Tran TAT, Johansson M, Bengtsson U, Ahlen G, Sällberg M, Grönlund H, van Hage M. Identification of galactose-a-1,3-galactose in the gastrointestinal tract of the tick Ixodes ricinus; possible relationship with red meat allergy. Allergy. 2013;68:549–52.

    Article  CAS  PubMed  Google Scholar 

  • Hegde VL, Venkatesh YP. Generation of antibodies specific to D-mannitol, a unique haptenic allergen, using reductively aminated d-mannose-bovine serum albumin conjugate as the immunogen. Immunobiology. 2007;212:119–28.

    Article  CAS  PubMed  Google Scholar 

  • Heinz R, Waltenbaugh C. Ethanol consumption modifies dendritic cell antigen presentation in mice. Alcohol Clin Res. 2007;31:1759–71.

    Article  CAS  Google Scholar 

  • Holzweber F, Svehla W, Fellner W, Dalik T, Stubler S, Hemmer W, Altmann F. Inhibition of IgE binding to cross-reactive carbohydrate determinants enhances diagnostic selectivity. Allergy. 2013;68:1269–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jappe U. Allergy to red meat. α-Gal: new epitope, new entity? Hautarzt. 2012;63:299–306.

    Article  CAS  PubMed  Google Scholar 

  • Jappe U. Delayed anaphylaxis due to hidden food allergens. Allergologie. 2015;37:265–74.

    Article  Google Scholar 

  • Jappe U, Raulf-Heimsoth M, Hoffmann M, Burow G, Hübsch-Müller C, Enk A. In vitro hymenoptera venom allergy diagnosis: improved by screening for cross-reactive carbohydrate determinants and reciprocal inhibition. Allergy. 2006;61:1220–9.

    Article  CAS  PubMed  Google Scholar 

  • Jappe U, Raulf-Heimsoth M. Allergologische In-vitro-Diagnostik und die kreuzreaktiven Kohlenhydratepitope. Allergo J. 2007;16:264–74.

    Article  Google Scholar 

  • Jappe U, Raulf-Heimsoth M. Kreuzreagierende Kohlenhydratdeterminanten (cross-reactive carbohydrate determinants, CCD) und ihre Bedeutung für die Allergiediagnostik. Allergologie. 2008;31:82–90.

    Article  Google Scholar 

  • Jappe U, Kreft B, Ludwig A, Przybilla B, Walker A, Biedermann T, Raulf-Heimsoth M, Sültz J, Becker WM, Petersen A. Aufbau und Anwendung eines sensitiven Verfahrens zum Nachweis von IgE-Antikörpern gegen das Kohlenhydratepitop Galactose-α-1,3-Galactose. Abstract Allergo J. 2011;20:33.

    Google Scholar 

  • Jin C, Hantusch B, Hemmer W, Stadlmann J, Altmann F. Affinity of IgE and IgG against cross-reactive carbohydrate determinants on plant and insect glycoproteins. J Allergy Clin Immunol. 2008;121:185–90.

    Article  CAS  PubMed  Google Scholar 

  • Kespohl S, Schlünssen V, Jacobsen G, Schaumburg I, Maryska S, Meurer U, Brüning T, Sigsgaard T, Raulf-Heimsoth M. Impact of cross-reactive carbohydrate determinants on wood dust sensitization. Clin Exp Allergy. 2010;40:1099–106.

    Article  CAS  PubMed  Google Scholar 

  • Kespohl S, Kotschy-Lang N, Tomm JM, von Bergen M, Maryska S, Brüning T, Raulf-Heimsoth M. Occupational IgE-mediated softwood allergy: characterization of the causative allergen. Int Arch Allergy Immunol. 2012;157:202–8.

    Article  CAS  PubMed  Google Scholar 

  • Linneberg A, Berg ND, Gonzalez-Quintela A, Vidal C, Elberling J. Prevalence of self-reported hypersensitivity symptoms following intake of alcoholic drinks. Clin Exp Allergy. 2008;38:145–51.

    Article  CAS  PubMed  Google Scholar 

  • Malandain H. IgE-reactive carbohydrate epitopes – classification, cross-reactivity, and clinical impact. Eur Ann Allergy Clin Immunol. 2005;37:122–8.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palacin A, Quirce S, Sánchez-Monge R, Fernández-Nieto M, Varela J, Sastre J, Salcedo G. Allergy to kiwi in patients with baker’s asthma: identification of potential cross-reactive allergens. Ann Allergy Asthma Immunol. 2008;101:200–5.

    Article  CAS  PubMed  Google Scholar 

  • Palacin A, Quirce S, Sanchez-Monge R, Bobolea I, Diaz-Perales A, Martin-Muñoz F, Pascual C, Salcedo G. Sensitization profiles to purified plant food allergens among pediatric patients with allergy to banana. Pediatr Allergy Immunol. 2011;22:186–95.

    Article  PubMed  Google Scholar 

  • Pastorello EA, Farioli L, Pravettoni V, Ortolani C, Fortunato D, Giuffrida MG, Perono Garoffo L, Calamari AM, Brenna O, Conti A. Identification of grape and wine allergens as an endochitinase 4, a lipid-transfer protein, and a thaumatin. J Allergy Clin Immunol. 2003;111:350–9.

    Article  CAS  PubMed  Google Scholar 

  • Qian J, Liu T, Yang L, Daus A, Crowley R, Zhou Q. Structural characterization of N-linked oligosaccharides on monoclonal antibody cetuximab by the combination of orthogonal matrix-assisted laser desorption/ionization hybrid quadrupole-quadrupole time-of-flight tandem mass spectrometry and sequential enzymatic digestion. Anal Biochem. 2007;364:8–18.

    Article  CAS  PubMed  Google Scholar 

  • Raulf-Heimsoth M, Rihs HP, Rozynek P, et al. Quantitative analysis of immunoglobulin E reactivity profiles in patients allergic or sensitized to natural rubber latex (Hevea brasiliensis). Clin Exp Allergy. 2007;37:1657–67.

    Article  CAS  PubMed  Google Scholar 

  • Raulf-Heimsoth M, Rihs HP. Latexallergene: Sensibilisierungsquellen und Einzelallergenprofile erkennen. Allergo J. 2011;20:241–3.

    Article  Google Scholar 

  • van Ree R, Cabanes-Macheteau M, Akkerdaas J, Milazzo JP, Loutelier-Bourhis C, Rayon C, Villalba M, Koppelman S, Aalberse R, Rodriguez R, Faye L, Lerouge P. Beta(1,2)-xylose and alpha(1,3)-fucose residues have a strong contribution in IgE binding to plant glycoallergens. J Biol Chem. 2000;275:11451–8.

    Article  PubMed  Google Scholar 

  • Roncati L, Barbolini G, Scacchetti AT, Busani S, Maiorana A. Unexpected death: anaphylactic intraoperative death due to thymoglobulin carbohydrate excipient. Forensic Sci Int. 2013;228:e28–32.

    Article  CAS  PubMed  Google Scholar 

  • Sampson HA, Ho D. Relationship between food-specific IgE-concentration and the risk of positive food challenges in children and adolescents. J Allergy Clin Immunol. 1997;100:444–51.

    Article  CAS  PubMed  Google Scholar 

  • Sampson HA. Utility of food-specific IgE-concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol. 2001;107:891–6.

    Article  CAS  PubMed  Google Scholar 

  • Sander I, Rozynek P, Rihs HP, van Kampen V, Chew FT, Lee WS, Kotschy-Lang N, Merget R, Brüning T, Raulf-Heimsoth M. Multiple wheat flour allergens and cross-reactive carbohydrate determinants bind IgE in baker’s asthma. Allergy. 2011;66:1208–15.

    Article  CAS  PubMed  Google Scholar 

  • Serghini-Idrissi N, Ravier I, Aucouturier H, Ait Tahar H, Sonneville A. Food allergy in the chronic alcoholic and alcohol in food allergy: apropos of 38 cases. Allergy Immunol (Paris). 2001;33:378–82.

    CAS  Google Scholar 

  • Takahashi H, Chinuki Y, Tanaka A, Morita E. Laminin γ-1 and collagen α-1 (VI) chain are galactose-α-1,3-galactose-bound allergens in beef. Allergy. 2014;69:199–207.

    Article  CAS  PubMed  Google Scholar 

  • Untersmayr E, Jensen-Jarolim E. The role of protein digestibility and antacids on food allergy outcomes. J Allergy Clin Immunol. 2008;121:1301–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vassilopoulou E, Zuidmeer L, Akkerdaas J, Tassios I, Rigby NR, Mills EN, van Ree R, Saxoni-Papageorgiou P, Papadopoulos NG. Severe immediate allergic reactions to grapes: part of a lipid transfer protein-associated clinical syndrome. Int Arch Allergy Immunol. 2007;143:92–102.

    Article  PubMed  Google Scholar 

  • Vidal C, Vizcaino L, Díaz-Peromingo JA, Garrido M, Gomez-Rial J, Linneberg A, Gonzalez-Quintela A. Immunoglobulin-E reactivity to a glycosylated food allergen (peanuts) due to interference with cross-reactive carbohydrate determinants in heavy drinkers. Alcohol Clin Exp Res. 2009;33:1322–8.

    Article  CAS  PubMed  Google Scholar 

  • Weber A, Schröder H, Thalberg K, März L. Specific interaction of IgE antibodies with a carbohydrate epitope of honey bee venom phospholipase A2. Allergy. 1987;42:464–70.

    Article  CAS  PubMed  Google Scholar 

  • Wiszniewska M, Zgorzelska-Kowalik J, NowakowskaSwirta E, Palczynski C, Walusiak-Skorupa J. Cross – reactive carbohydrate determinants in diagnostics of occupational allergy – preliminary results. Allergy. 2010;65:664–6.

    Article  CAS  PubMed  Google Scholar 

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Jappe, U., Raulf, M. (2017). Cross-Reactive Carbohydrate Determinants: Diagnostic and Clinical Relevance. In: Kleine-Tebbe, J., Jakob, T. (eds) Molecular Allergy Diagnostics. Springer, Cham. https://doi.org/10.1007/978-3-319-42499-6_6

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