Allergenicity assessment of genetically modified organisms (GMOs )

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  • Allergenicity assessment of genetically modified organisms (GMOs)

  • Some important definitions:

    Allergy: Overwhelming pathological reactions of the body due to intercurrent contact with antigens Clemens von Pirquet 1906

    IgE-mediated allergy is the most frequent form of allergy, but many other forms exist (e.g., celiac disease, immune complex diseases-Type III, cell-mediated forms of allergy-Type IV)

    Allergenic activity: Induction of an allergic reaction in allergic individual

    Allergenicity: Induction of allergy in a not yet allergic individual (i.e., sensitization and induction of allergic reactions)

  • Assessment of the allergenic potential of foods derived from biotechnology FAO/WHO decision tree

  • Current practice in the assessment of the allergenicity of GMOs

    Mainly arguments but rarely experiments

    Arguments against the allergenic potential of a GMO

    Lack of sequence homology with known allergens Inserted gene is expressed only at low levels Easily digestable protein Protein source is not an allergen source Lack of glycolsylation

  • Sequence comparisons are not suitable for predicting or excluding allergenicity with certainty

  • Human IgE and T cell reactivity patterns of Bet v 1isoforms a, e, b, d, and l Isoforms of the major birch pollen allergen, Bet v 1 without allergic activity

  • T1, a Bet v 1-homologous plant protein without allergenic activity

  • T1, a Bet v 1-homologous plant protein without allergenic activity

  • The level of expression is not associated with allergenicity

    Example: Profilin, a potent cross-reactive plant allergen is expressed at low levels

  • Resistance to proteolytic digestion does not predict allergenicity

    Example: Pollen contains trypsin-labile as well as trypsin-resistant allergens

  • Glycosylation does not predict allergenicityExample: Phl p 7, a potent allergen from timothy grass pollen is not glycosylated

  • Pleiotropic effects affecting the overall allergenicity of the GMO must be considered

    Example: Upregulation of profilin expression during pollen maturation

  • The expression of PR-proteins, which represent important allergens, is regulated by various factors

  • Allergenic activity and allergenicity need to be assessed: Induction of allergic responses in experimental animal models

  • Suggestion:

    Evaluation of allergenicity by standardized experimental procedures

    Develop procedures for allergenicity assessment which can be applied for GMOs as well as for any other new organism

  • Investigation of the allergenic activity in allergic patients: IgE reactivity of extracts from GMOs and from the wildtype

    Assessment of allergenicity: Induction of IgE responses in animals with extracts from GMOs and from the wildtype

    Allergenic activity Investigation of whole GMOsNoYes

    Allergenicity

  • Thanks to:

    Armin Spk, Inter-University Research Center for Technology, Work and Culture, Graz, Austria.

    Helmut Gaugitsch, Federal Environment Agency, Vienna, Austria.

    Sylvia Laffer, Dept. of Pathophysiology, University of Vienna, Austria.

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