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Allergenicity assessment of genetically modified crops—what makes sense?

Nature Biotechnology volume 26, pages 73–81 (2008)Cite this article

An Erratum to this article was published on 01 February 2008

Abstract

GM crops have great potential to improve food quality, increase harvest yields and decrease dependency on certain chemical pesticides. Before entering the market their safety needs to be scrutinized. This includes a detailed analysis of allergenic risks, as the safety of allergic consumers has high priority. However, not all tests currently being applied to assessing allergenicity have a sound scientific basis. Recent events with transgenic crops reveal the fallacy of applying such tests to GM crops.

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Figure 1: Schematic interpretation of the weight-of-evidence approach described by the Codex Alimentarius Commission Guidelines for Allergenicity Assessment in 2003 (ref. 1).

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References

  1. Codex Alimentarius Commission. Alinorm 03/34: Joint FAO/WHO Food Standard Programme, Codex Alimentarius Commission, Twenty-Fifth Session, Rome, 30 June–5 July, 2003. Appendix III, Guideline for the conduct of food safety assessment of foods derived from recombinant-DNA plants and Appendix IV, Annex on the assessment of possible allergenicity, pp. 47–60 (2003).

  2. Sampson, H.A. Food allergy—accurately identifying clinical reactivity. Allergy 60 S79, 19–24 (2005).

    Article  Google Scholar 

  3. Taylor, S.L. Review of the development of methodology for evaluating the human allergenic potential of novel proteins. Mol. Nutr. Food Res. 50, 604–609 (2006).

    Article  CAS  Google Scholar 

  4. Nordlee, J.A., Taylor, S.L., Townsend, J.A., Thomas, J.A. & Bush, R.K. Identification of a Brazil-nut allergen in transgenic soybeans. N. Engl. J. Med. 334, 688–692 (1996).

    Article  CAS  Google Scholar 

  5. Metcalfe, D.D. et al. Assessment of the allergenic potential of foods derived from genetically modified crop plants. Crit. Rev. Food Sci. Nutr. 36(S), 165–186 (1996).

    Article  Google Scholar 

  6. FAO/WHO. Evaluation of allergenicity of genetically modified foods. Report of a joint FAO/WHO expert consultation on allergenicity of foods derived from biotechnology. (Food and Agriculture Organization of the United Nations (FAO), Rome, 2001.

  7. Goodman, R.E., Hefle, S.L., Taylor, S.L. & van Ree, R. Assessing genetically modified crops to minimize the risk of increased food allergy: a review. Int. Arch. Allergy Immunol. 137, 153–166 (2005).

    Article  CAS  Google Scholar 

  8. Aalberse, R.C. Structural biology of allergens. J. Allergy Clin. Immunol. 106, 228–238 (2000).

    Article  CAS  Google Scholar 

  9. Ladics, G.S., Bannon, G.A., Silvanovich, A. & Cressman, R.F. Comparison of conventional FASTA identity searches with the 80 amino acid sliding window FASTA search for elucidation of potential identities to known allergens. Mol. Nutr. Food Res. 51, 985–998 (2007).

    Article  CAS  Google Scholar 

  10. Goodman, R.E. & Hefle, S.L. Gaining perspective on the allergenicity assessment of genetically modified crops. Expert Opin. Immunol. 1, 561–578 (2005).

    Article  CAS  Google Scholar 

  11. Goodman, R.E. & Wise, J. Predicting the allergenicity of novel proteins in genetically modified organisms. in Food Allergy (eds. Maleki S.J. et al.) 219–247 (American Society of Microbiology Press, Washington, DC, 2006).

    Chapter  Google Scholar 

  12. Hileman, R.E. et al. Bioinformatic methods for allergenicity assessment using a comprehensive allergen database. Int. Arch. Allergy Immunol. 128, 280–291 (2002).

    Article  CAS  Google Scholar 

  13. Stadler, M.B. & Stadler, B.M. Allergenicity prediction by protein sequence. FASEB J. 17, 1141–1143 (2003).

    Article  CAS  Google Scholar 

  14. Silvanovich, A. et al. The value of short amino acid sequence matches for prediction of protein allergenicity. Toxicol. Sci. 90, 252–258 (2006).

    Article  CAS  Google Scholar 

  15. Sten, E. et al. A comparative study of the allergenic potency of wild-type and glyphosate-tolerant gene-modified soybean cultivars. APMIS 112, 21–28 (2004).

    Article  CAS  Google Scholar 

  16. Ladics, G.S., Bardina, L., Cressman, R.F., Mattsson, J.L. & Sampson, H.A. Lack of cross-reactivity between the Bacillus thuringiensis derived protein Cry1F in maize grain and dust mite Der p7 protein with human sera positive for Der p7-IgE. Regul. Toxicol. Pharmacol. 44, 136–143 (2006).

    Article  CAS  Google Scholar 

  17. van Ree, R. Carbohydrate epitopes and their relevance for the diagnosis and treatment of allergic disease. Int. Arch. Allergy Immunol. 129, 189–197 (2002).

    Article  CAS  Google Scholar 

  18. Altmann, F. The role of protein glycosylation in allergy. Int. Arch. Allergy Immunol. 142, 99–115 (2007).

    Article  CAS  Google Scholar 

  19. Asero, R. et al. IgE-mediated food allergy diagnosis: current status and new perspectives. Mol. Nutr. Food Res. 51, 135–147 (2007).

    Article  CAS  Google Scholar 

  20. Astwood, J.D., Leach, J.N. & Fuchs, R.L. Stability of food allergens to digestion in vitro. Nat. Biotechnol. 14, 1269–1273 (1996).

    Article  CAS  Google Scholar 

  21. Thomas, K. et al. A multi-laboratory evaluation of a common in vitro pepsin digestion assay protocol used in assessing the safety of novel proteins. Regul. Toxicol. Pharmacol. 39, 87–98 (2004).

    Article  CAS  Google Scholar 

  22. Asero, R. et al. Lipid transfer protein: a pan-allergen in plant-derived foods that is highly resistant to pepsin digestion. Int. Arch. Allergy Immunol. 122, 20–32 (2000).

    Article  CAS  Google Scholar 

  23. Fu, T.J., Abbott, U.R. & Hatzos, C. Digestibility of food allergens and nonallergenic proteins in simulated gastric fluid and simulated intestinal fluid—a comparative study. J. Agric. Food Chem. 50, 7154–7160 (2002).

    Article  CAS  Google Scholar 

  24. Yagami, T., Haishima, Y., Nakamura, A., Osuna, H. & Ikezawa, Z. Digestibility of allergens extracted from natural rubber latex and vegetable foods. J. Allergy Clin. Immunol. 106, 752–762 (2000).

    Article  CAS  Google Scholar 

  25. Aalberse, R.C. & Stapel, S.O. Structure of food allergens in relation to allergenicity. Pediatr. Allergy Immunol. 12 Suppl 14, 10–14 (2001).

    Article  Google Scholar 

  26. Vassilopoulou, E. et al. Severe immediate allergic reactions to grapes: part of a lipid transfer protein-associated clinical syndrome. Int. Arch. Allergy Immunol. 143, 92–102 (2007).

    Article  Google Scholar 

  27. Pastorello, E.A. et al. Identification of hazelnut major allergens in sensitive patients with positive double-blind, placebo-controlled food challenge results. J. Allergy Clin. Immunol. 109, 563–570 (2002).

    Article  Google Scholar 

  28. Breiteneder, H. & Radauer, C. A classification of plant food allergens. J. Allergy Clin. Immunol. 114, 127–130 (2004).

    Article  Google Scholar 

  29. Untersmayr, E. et al. The effects of gastric digestion on codfish allergenicity. J. Allergy Clin. Immunol. 115, 377–382 (2005).

    Article  CAS  Google Scholar 

  30. Bannon, G.A. et al. Digestive stability in the context of assessing the potential allergenicity of food proteins. Comments Toxicol. 8, 271–285 (2002).

    Article  CAS  Google Scholar 

  31. Burks, A.W. & Fuchs, R.L. Assessment of the endogenous allergenicity in glyphosate-tolerant and commercial soybean varieties. J. Allergy Clin. Immunol. 96, 1008–1010 (1995).

    Article  CAS  Google Scholar 

  32. Lehrer, S.B. & Reese, G. Recombinant proteins in newly developed foods: identification of allergenic activity. Int. Arch. Allergy Immunol. 113, 122–124 (1997).

    Article  CAS  Google Scholar 

  33. Gao, Z.S. et al. Genomic cloning and linkage mapping of Mal d 1 (PR-10) gene family in apple (Malus domestica). Theor. Appl. Genet. 111, 171–183 (2005).

    Article  CAS  Google Scholar 

  34. Carnes, J., Ferrer, A. & Fernandez-Caldas, E. Allergenicity of 10 different apple varieties. Ann. Allergy Asthma Immunol. 96, 564–570 (2006).

    Article  CAS  Google Scholar 

  35. Zuidmeer, L. Allergenicity assessment of apple cultivars: hurdles in quantifying labile fruit allergens. Int. Arch. Allergy Immunol. 141, 230–240 (2006).

    Article  CAS  Google Scholar 

  36. Codina, R., Ardusso, L., Lockey, R.F., Crisci, C. & Medina, I. Allergenicity of varieties of soybean. Allergy 58, 1293–1298 (2003).

    Article  CAS  Google Scholar 

  37. Sancho, A.I. et al. Maturity and storage influence on the apple (Malus domestica) allergen Mal d 3, a nonspecific lipid transfer protein. J. Agric. Food Chem. 54, 5098–5104 (2006a).

    Article  CAS  Google Scholar 

  38. Sancho, A.I. et al. Effect of postharvest storage on the expression of the apple allergen Mal d 1. J. Agric. Food Chem. 54, 5917–5923 (2006b).

    Article  CAS  Google Scholar 

  39. Marzban, G. et al. Localization and distribution of the major allergens in apple fruits. Plant Sci. 169, 387–394 (2005).

    Article  CAS  Google Scholar 

  40. Jenkins, J.A., Griffiths-Jones, S., Shewry, P.R., Breiteneder, H. & Mills, E.N.C. Structural relatedness of plant food allergens with specific reference to cross-reactive allergens: an in silico analysis. J. Allergy Clin. Immunol. 115, 163–170 (2005).

    Article  CAS  Google Scholar 

  41. Ibanez, M.D., Marinez, M., Sanchez, J.J. & Fernandez-Caldas, E. Legume cross-reactivity (in Spanish). Allergol. Immunopathol. (Madr.) 31, 151–161 (2003).

    Article  CAS  Google Scholar 

  42. Bindslev-Jensen, C., et al. Assessment of the potential allergenicity of ice structuring protein type III HPLC 12 using the FAO/WHO 2001 decision tree for novel foods. Food Chem. Toxicol. 41, 81–87 (2003).

    Article  CAS  Google Scholar 

  43. Ferriera, F., Hawranek, T., Gruber, P., Wopfner, N. & Mari, A. Allergic cross-reactivity: from gene to the clinic. Allergy 59, 243–267 (2004).

    Article  Google Scholar 

  44. Dearman, R.J. & Kimber, I. A mouse model for food allergy using intraperitoneal sensitization. Methods 41, 91–98 (2007).

    Article  CAS  Google Scholar 

  45. McClain, S. & Bannon, G.A. Animal models of food allergy: opportunities and barriers. Curr. Allergy Asthma Rep. 6, 141–144 (2006).

    Article  Google Scholar 

  46. Matsuda, T., Matsubara, T. & Hino, S. Immunogenic and allergenic potentials of natural and recombinant innocuous proteins. J. Biosci. Bioeng. 101, 203–211 (2006).

    Article  CAS  Google Scholar 

  47. Perzanowski, M.S., Ronmark, E., Nold, B., Lundback, B. & Platts-Mills, T.A. Relevance of allergens from cats and dogs to asthma in the northernmost province of Sweden: schools as a major site of exposure. J. Allergy Clin. Immunol. 103, 1018–1024 (1999).

    Article  CAS  Google Scholar 

  48. Fernandez-Rivas, M. et al. Apple allergy across Europe: how allergen sensitization profiles determine the clinical expression of allergies to plant foods. J. Allergy Clin. Immunol. 118, 481–488 (2006).

    Article  CAS  Google Scholar 

  49. Reuter, A. et al. A critical assessment of allergen component-based in vitro diagnosis in cherry allergy across Europe. Clin. Exp. Allergy 36, 815–823 (2006).

    Article  CAS  Google Scholar 

  50. Herouet, C. et al. Safety evaluation of the phosphinothricin acetyltransferase proteins encoded by the pat and bar sequences that confer tolerance to glufosinate-ammonium herbicide in transgenic plants. Regul. Toxicol. Pharmacol. 41, 134–149 (2005).

    Article  CAS  Google Scholar 

  51. Jones, S.M., Magnolfi, C.F., Cooke, S.K. & Sampson, H.A. Immunologic cross-reactivity among cereal grains and grasses in children with food hypersensitivity. J. Allergy Clin. Immunol. 96, 341–351 (1995).

    Article  CAS  Google Scholar 

  52. Ikematsu, K., Tachimoto, H., Sugiasaki, C., Syukuya, A. & Ebisawa, M. Feature of food allergy developed during infancy (1)—relationship between infantile atopic dermatitis and food allergy (in Japanese). Arerugi 55, 140–150 (2006).

    PubMed  Google Scholar 

  53. Morton, R.L. et al. Bean alpha-amylase inhibitor 1 in transgenic peas (Pisum sativum) provides complete protection from pea weevil (Bruchus pisorum) under field conditions. Proc. Natl. Acad. Sci. USA 97, 3820–3825 (2000).

    Article  CAS  Google Scholar 

  54. Prescott, V.E. et al. Transgenic expression of bean alpha-amylase inhibitor in peas results in altered structure and immunogenicity. J. Agric. Food Chem. 53, 9023–9030 (2005).

    Article  CAS  Google Scholar 

  55. Editorial. Genetically modified mush. Nat. Biotechnol. 24, 2 (2006).

  56. Sinagawa-Garcia, S.R. et al. Safety assessment by in vitro digestibility and allergenicity of genetically modified maize with Amaranth 11S globulin. J. Agric. Food Chem. 52, 2709–2714 (2004).

    Article  CAS  Google Scholar 

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Acknowledgements

The preparation of this article was conducted with a contribution of the University of Nebraska Agricultural Research Division, supported in part by funds provided through the US Department of Agriculture. Additional support was provided by the Food Allergy Research and Resource Program. Mention of a trade name, proprietary products or company name is for presentation clarity and does not imply endorsement by the authors. R.E.G. acknowledges Bayer CropScience for providing funds to support research for evaluating methods to compare endogenous allergenicity of crop varieties through research at the University of Nebraska. S.V. acknowledges Monsanto Company for supporting studies on the bio-variability of the allergenic potential of soybean varieties in comparison to transgenic lines.

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Authors and Affiliations

  1. Department of Food Science & Technology, University of Nebraska, Lincoln, 68583-0955, Nebraska, USA

    Richard E Goodman & Steve L Taylor

  2. Department of Allergology, Paul-Ehrlich-Institut, Langen, D-63225, Germany

    Stefan Vieths

  3. Division of Pediatric Allergy and Immunology, Mount Sinai Medical Center, New York, 10029, New York, USA

    Hugh A Sampson

  4. Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, 3052, Victoria, Australia

    David Hill

  5. Division Pediatric Allergy, National Sagamihara Hospital, Sagamihara, 228-8522, Japan

    Motohiro Ebisawa

  6. Department of Experimental Immunology, Academic Medical Center, Amsterdam, 1105, AZ, The Netherlands

    Ronald van Ree

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Correspondence to Richard E Goodman.

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Competing interests

Authors affiliated with the University of Nebraska declare that six international biotechnology companies (BASF, Bayer CropScience, Dow AgroSciences, DuPont/Pioneer, Monsanto Company and Syngenta CropProtection) cosponsor the AllergenOnline database, which was developed and is maintained at the University of Nebraska.

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Goodman, R., Vieths, S., Sampson, H. et al. Allergenicity assessment of genetically modified crops—what makes sense?. Nat Biotechnol 26, 73–81 (2008). https://doi.org/10.1038/nbt1343

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