Creation of the First Comparative Gluten Allergenicity Map Using a Mouse Model: A Preclinical Tool to Establish Substantial Equivalence of Novel Wheat Glutens

Gluten allergy is linked to high risk of anaphylaxis. The relative allergenicity of glutens (alcohol-soluble gliadin and acid-soluble glutenin) from the three commercially grown wheat species (diploid Triticum monococcum, tetraploid Triticum durum, hexaploid Triticum aestivum) is unknown. A comparative gluten allergenicity map (CGAM) from these species will enable the identification of potentially hyper-/hypo-/iso-allergenic species/varieties of wheat as well as the determination of substantial equivalence of genetically engineered (GE) or other novel wheat lines. Here, using a recently described novel mouse model, we tested the hypothesis that the three different wheat species will exhibit natural variation in their gluten allergenicity. Groups of Balb/c mice were transdermally sensitized to alcohol-soluble or acid-soluble gluten extracts followed by elicitation of systemic anaphylaxis. Initial studies were performed to validate the model for glutens from the three wheat species. Both glutens from all three wheat species elicited robust specific IgE responses, as well as systemic anaphylaxis. However, comparative mapping analysis revealed differences in capacity to elicit specific IgE among the three wheat species with T. aestivum being the most potent in both gluten extracts. Hypothermic shock response analysis revealed that the three species elicited similar kinetics and intensity of anaphylaxis. Nevertheless, when analyzing mucosal mast cell response, it was revealed that the glutens from T. aestivum emerged as the most potent elicitor. Collectively, these results yield the first CGAM that may be utilized for preclinical testing of the allergenic potential of glutens from novel (e.g., GE) wheats and processed wheat products against existing wheat glutens.