Cross-IgE sensitization correlates with cross-anaphylaxis among peanut and multiple tree nuts in a murine model

Background: The incidence of multiple food allergies (MFA), defined as exhibiting allergic responses to two or more distinct food groups, has been increasing. Since peanut (PN)/ tree nuts (TN) MFA causes severe reactions, it is challenging to study cross-reactivity immediately using human subjects. Development of a PN/TN cross-reactivity model may provide a useful tool to understand the immunological mechanisms underlying cross-reactivity among PN/TN, and a tool to develop therapies that prevent cross-reactivity. Methods: Sensitization to the most common allergens, PN, walnut (WN), and cashew (CSH), were utilized for cross-reactive sensitization to eight other TNs (almond, pecan, pistachio, hazelnut, Brazil nut, pine nut, macadamia but, and coconut). C3H/ HeJ mice were intraperitoneally sensitized (primed) with a mixture of PN, WN, and CSH and specific (s)- IgE levels against the primed and cross-reactive TN antigens were determined. Intragastric challenges with each primed and eight unprimed allergens were performed and anaphylaxis symptoms measured. Correlation of primed IgE levels and symptoms scores with primed and unprimed allergen were conducted. Results: PN, WN, and CSH sensitization induced significant cross reactivity against other TNs, with elevated sIgE levels against both primed and unprimed allergens. Cross-reactivity was confirmed clinically, with anaphylaxis upon primed and unprimed nut challenges, exhibiting strong positive correlations among sIgE levels and anaphylaxis observed. Conclusion: Interestingly, as seen with patients, different priming nuts were capable of cross-sensitization against different groups of challenge nuts. Thus, we present a model system that can be developed to investigate the molecular basis of MFA and potential therapeutic approaches.