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Explore the complexities of allergenicity assessment in GMOs, vital definitions, current practices, and experimental approaches. Learn about key factors influencing allergenic potential and the importance of standardized procedures in evaluation.
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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 1906IgE-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 individualAllergenicity: Induction of allergy in a not yet allergic individual (i.e., sensitization and induction of allergic reactions)
Source of gene allergenic Yes Noo Sequence Homology Sequence Homology Yes No Yes No Specific Serum Screen Target Serum Screen No Yes Yes No Pepsin Resistance & Animal Models Yes Yes Yes +/+ +/- -/- High Low Probability of Allergenicity Likely Allergenic 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
IgE binding (rel. %) Skin prick test wheal areas (mm2) T cell reactivity (rel. %) nBet v 1 100 100 ND rBet v 1a 41 100 70 rBet v 1e 67 83 50 rBet v 1b 92 60 19 rBet v 1d 100 5 7 rBet v 1l 87 3 10 Isoforms of the major birch pollen allergen, Bet v 1 without allergic activity Human IgE and T cell reactivity patterns of Bet v 1 isoforms a, e, b, d, and l
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 allergenicity Example: 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 whole GMOs Investigation of the allergenic activity in allergic patients: IgE reactivity of extracts from GMOs and from the wildtype Yes No Assessment of allergenicity: Induction of IgE responses in animals with extracts from GMOs and from the wildtype Allergenic activity Allergenicity
Thanks to: Armin Spök, 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.