A mouse model of walnut allergy mimics key features of the human disease
Monday, March 5, 2018
South Hall A2 (Convention Center)
Michael D. Kulis Jr., PhD, Kelly Orgel, BS, Johanna Smeekens, PhD, Soheila J. Maleki, PhD FAAAAI, Barry K. Hurlburt, PhD, Kenneth Bagley, PhD
RATIONALE: Tree nut allergies are not typically outgrown and can lead to life-threatening anaphylaxis. A mouse model of walnut allergy that replicates features of the clinical condition would be a valuable tool to generate pre-clinical data for novel therapeutic approaches aimed at treating walnut and other tree nut allergies.

METHODS: A Collaborative Cross mouse strain was used to develop a mouse model of walnut allergy. Mice were sensitized to walnut once per week for four weeks by intragastric feeding of walnut extract plus cholera toxin. Mice were bled post-sensitization and allergen-specific IgE was quantified by ELISA. Finally, mice underwent oral challenges with walnut, pecan, or egg.

RESULTS: Mice sensitized to walnut produced IgE against walnut extract, the major walnut allergens Jug r 1 and Jug r 2, and pecan extract, but not to egg proteins. Walnut- and pecan-IgE were highly correlated (Spearman r=0.824, p<0.0001) as is seen in allergic patients. Oral challenges with walnut and pecan produced severe reactions with mean body temperature decreases of 5.3°C and 4.7°C, respectively, along with overt allergic symptoms including labored breathing, diarrhea, and reduced activity.

CONCLUSIONS: Walnut-sensitized mice generate IgE against the major walnut allergens, IgE cross-reacts with pecan allergens, and mice experience anaphylaxis to walnut as well as pecan, thus replicating important immunologic characteristics typical of walnut allergic patients. This model will provide a platform for developing immunotherapy for walnut and pecan allergies.