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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)
Source of gene allergenic
Yes
YesYes
Yes
Noo
Sequence Homology
Sequence Homology
Target SerumScreen
Specific Serum Screen
NoNo
Pepsin Resistance &
Animal Models
No
+/+ +/- -/-High Low
Probability of Allergenicity
LikelyAllergenic
Yes Yes
No
Yes Yes
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
Human IgE and T cell reactivity patterns of Bet v 1
isoforms a, e, b, d, and l
T cell reactivity(rel. %)
IgE binding(rel. %)
Skin prick testwheal areas(mm2)
nBet v 1 100 100 ND
rBet v 1a 41 100 70
rBet v 1e 67 83 50
rBet v 1l 87 3 10
rBet v 1d 100 5 7
rBet v 1b 92 60 19
Isoforms of the major birch pollen allergen, Bet v 1 without allergic 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
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 GMOs
NoYes
Allergenicity