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Allergenicity of cry9c: An unresolved issue

2001; Elsevier BV; Volume: 108; Issue: 4 Linguagem: Inglês

10.1067/mai.2001.118513

1097-6825

Jonathan A. Bernstein, Jonathan A. Bernstein, David I. Bernstein,

Food Allergy and Anaphylaxis Research

As appropriately emphasized by Taylor and Hefle1Taylor SL Hefle SL Will genetically modified foods be allergenic?.J Allergy Clin Immunol. 2001; 107: 765-771Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar in their recent article on genetically modified (GM) foods, the goals of modern agricultural biotechnology are to replace chemical pesticides and herbicides, to improve crop yields, and to alleviate hunger in developing countries. Despite these lofty antipollution and nutritional advantages, the acceptance of novel GM foods by consumers across the globe is not yet uniform. One of the concerns by consumer groups is the potential allergenicity of novel GM foods, particularly those containing encoded proteins to which human beings have not previously been exposed. This has become a contentious issue not only for consumers but also for food technology scientists and allergists/immunologists. Taylor and Hefle advocate a scientific consensus for defining allergenicity of novel GM foods in the context of the International Food Biotechnology Council (IFBC) algorithm, which considers the source of the gene, amino acid sequence, homology, physicochemical properties, level of expression of the encoded protein, and clinical diagnostic methods. In selecting the “StarLink situation” as an example of how this algorithm could be implemented, Taylor and Hefle concluded that cry9c protein in GM corn was nonallergenic—this on the basis of suppositions that it was neither structurally homologous to known food or environmental allergens nor present in sufficient quantities to elicit allergic sensitization. They failed to note that cry9c is one of a family of closely related pesticidal endotoxins derived from Bacillus thuringiensis kurstaki (Btk), a nonpathogenic organism.2Schnepf E Crickmore N Van Rie J Lereclus D Baum J Feitelson J et al.Bacillus thuringiensis and its pesticidal crystal proteins.Microbiol Mol Biol Rev. 1998; 62: 775-806Crossref PubMed Google Scholar These Btk protoxins are not toxic to mammals or human beings. However, we recently demonstrated positive prick/puncture skin test results and serum-specific IgE to Btk spore and parasporal extracts containing these agents (cry1Ab and cry1Ac) in migrant farm workers recently exposed to pesticidal sprays.3Bernstein IL Bernstein JA Miller ME Terzieva S Lummus Z Bernstein DI et al.Immune responses in farm workers after exposure to B. thuringiensis pesticides.Environ Health Perspect. 1999; 107: 575-582Crossref PubMed Scopus (92) Google Scholar In addition, a specific IgE anamnestic response was observed. None of the workers manifested symptoms related to respiratory exposure, though we were not able to conduct follow-up studies for possible future symptoms. The IgE-mediated sensitivity induced by these cry1A protoxins could therefore theoretically be extended to cry9c, which has extensive phylogenetic amino acid sequence similarity with the cry1A class of endotoxins.2Schnepf E Crickmore N Van Rie J Lereclus D Baum J Feitelson J et al.Bacillus thuringiensis and its pesticidal crystal proteins.Microbiol Mol Biol Rev. 1998; 62: 775-806Crossref PubMed Google Scholar In comparison with cry1A, cry9c is very stable to both heat and gastric digestion—characteristics shared by known food allergens. Quantitatively, it is a minor component of GM corn (0.0129% equivalent to approximately 10 μg per ear). However, allergic potential cannot be dismissed entirely on this basis, because small doses (10-50 μg) of intragastric antigens favor systemic immunity rather than oral tolerance in rodent models.4Lamont AG Mowat AMCI Parrott DMV Printing of systemic and local delayed-type hypersensitivity responses by feeding low doses of ovalbumin to mice.Immunology. 1989; 66: 595-599PubMed Google Scholar Unfortunately, rodent models are not predictive of food allergenicity, because oral antigens given intragastrically in these animals require either encapsulation to escape gastric digestion or the use of concurrent adjuvants. Concerning the latter effect, it is of interest that the cry1A class of endotoxins is as potent an adjuvant as cholera toxin when administered intragastrically together with antigen in rodents.5Vazquez-Padron RI Moreno-Fierros L Neri-Bazan L De La Riva GA Loez-Revilla R Bacillus thuringiensis Cry1Ac protoxin is a potent systemic and mucosal adjuvant.Scand J Immunol. 1999; 49: 578-584Crossref PubMed Scopus (66) Google Scholar Soon after cry9c was detected in the human food chain, there were multiple consumer complaints, only some of which suggest an allergic component. These cases are currently being evaluated by the US Food and Drug Administration, and the results are as yet unknown. For these reasons, the potential allergenicity of cry9c and related cry1A endotoxins cannot be arbitrarily discounted. Indeed, interpretation of the currently available data in toto reveals that oral allergenicity of this GM protein has been neither proved nor disproved. This contrary view also illustrates that allergenicity of novel food proteins must be investigated on a case-by-case basis. Furthermore, in our opinion, the oral allergenicity (or lack thereof) of cry9c and related cry proteins in GM foods now requires independent prospective and controlled ingestion trials in human beings. To restore consumer confidence in the benefits of GM foods, it is essential that the cry9c allergen controversy be resolved by an objectively oriented clinical investigation that could be incorporated into future IFBC-based decision tree analysis of GM novel proteins. 1/8/118513