[Animal models for assessment of GMO allergenicity: advantages and limitations].
Incidence of IgE-mediated allergic reactions to foods is increasing as well as the severity of associated symptoms and numerous foods are now incriminated, probably in relation with modifications of dietary habits and increased exposure to new or modified food ingredients. Therefore, the introduction on the market of food composed of or derived from genetically modified organisms (GMOs) raised the question of their potential allergenicity. Particularly with regards to the allergenicity of a newly expressed protein, it is necessary to obtain, from several steps in the risk assessment process, a cumulative body of evidence which minimises any uncertainty. This may include the use of animal model despite no fully reliable validated model is available yet. Such animal models should allow to address 3 major issues: Is the novel protein a sensitizer, i.e. does it possess intrinsic properties that allow to sensitize a predisposed individual? Is the protein an elicitor i.e. is it able to elicit an allergic reaction in a sensitised individual? And is the protein an adjuvant, i.e. can it facilitate or enhance the sensitisation to an other protein? Animal models under investigation currently include mice, rats and guinea pigs but models such as dogs and swine also appeared a few years ago. The aim is to mimic the mechanism and characteristics of the sensitisation phase and/or the elicitation phase of the allergic reaction as it occurs in atopic humans. They are necessary because sensitisation studies can obviously not be done in human and because in vitro tests cannot reproduce the complexity of the immune system. We propose a mouse model which mimics both phases of the allergic reaction. It has permitted to evidence that biochemical and clinical manifestations occuring during the active phases of the allergic reaction differ according to the structure of the allergen used for the challenge. This may allow to compare the allergenic potential of a genetically modified protein with that of the conventional one and to identify possible unintended effects. However, pathogenesis of food allergy in human is very complex and multifactorial, including individual differences in susceptibility, environmental factors, conditions of exposure, ... No animal model can take into account all these factors and allow a reliable prediction of the prevalence and severity of allergic reactions which would result from the exposure to a (novel) protein. Nevertheless, point by point analysis using the different models available may provide useful informations on the potential allergenicity of a novel protein.
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Laboratoire d'Immuno-Allergie Alimentaire, INRA, CEA-Service de Pharmacologie et d'Immunologie CEA de Saclay, 91191 Gif-sur-Yvette.
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D000276:Adjuvants, Immunologic; D000818:Animals; D004285:Dogs; D005512:Food Hypersensitivity / Q000209:etiology / Q000276:immunology*; D006168:Guinea Pigs; D006241:Haptens / Q000276:immunology; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology; D051379:Mice; D023421:Models, Animal; D030781:Organisms, Genetically Modified / Q000276:immunology*; D051381:Rats; D013045:Species Specificity; D013552:Swine
D000276:Adjuvants, Immunologic; D006241:Haptens; D007073:Immunoglobulin E