Gender and dose dependent ovalbumin induced hypersensitivity responses in murine model of food allergy

Authors: Toomer, Ondulla; PEREIRA, MARION - Food And Drug Administration(FDA); DO, ANDREW - Food And Drug Administration(FDA); WILLIAMS, KRISTINA - Food And Drug Administration(FDA)

Submitted to: Journal of Food, Nutrition and Population Health
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/30/2016
Publication Date: 1/10/2017
Citation: Toomer, O.T., Pereira, M., Do, A., Williams, K. 2017. Gender and dose dependent ovalbumin induced hypersensitivity responses in murine model of food allergy. Journal of Food, Nutrition and Population Health. 1:1-6.

Interpretive Summary: Food allergies are prevalent in the US. Avoidance of the offending food is the only method of disease prevention. Despite regulations mandating the labeling of 8 major food allergens (FALCPA), undetected allergens are responsible for many adverse health events and recalls. Allowable threshold levels have not been established for the purposes of allergen labeling or detection, or for the prevention of an allergic reaction. Understanding the biological mechanisms of food allergy could help to define regulatory threshold levels using animal models that mimic host allergic responses. This study demonstrates and suggests gender specific dose-responses that may also exist among the food allergic population.

Technical Abstract: While federal regulations mandate the labeling of major food allergens, allowable food allergen thresholds have yet to be determined. Therefore the aim of this project was to identify the lowest egg allergen ovalbumin (OVA) dose causing hypersensitization using a validated murine model. Mice were orally sensitized for 5 weeks with 250 µg OVA + 10 µg cholera toxin (CT). At 6 weeks, mice were orally challenged the following treatment groups; Treatment 1-Control, Treatment 2-PBS, Treatment 3- 1mg OVA, Treatment 4-40 mg OVA, Treatment 5-75 mg OVA in 0.5 mL of PBS. Post-oral challenge, mice were euthanized and blood samples were analyzed for plasma IgE levels. Splenic lymphocytes were determined using FACS analysis. OVA sensitized mice had slightly elevated rectal temperatures post sensitization as compared to the controls. Male mice orally challenged with 1 mg OVA had approximately a 3 fold increase in plasma OVA IgE levels compared to female mice orally challenged with 1 mg OVA. Moreover, male mice orally challenged with 1 mg OVA, and all mice orally challenged with 40 mg OVA were severely hypothermic post OVA challenge, while mice orally challenged with 1 mg OVA did not display any clinical symptoms of allergy post challenge. All mice orally challenged with 40 mg OVA and 75 mg OVA had anaphylactic scores of 2 or greater with the highest score of 5 (tremor and convulsion). These results suggest that gender may strongly influence food allergen sensitization mechanisms and should be further explored.