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

Authors: MASKEY, ANISH - New York Medical College; CARANZZA, MICHELLE - General Nutraceutical Technology, Llc; KOPULOS, DANIEL - New York Medical College; SPEARS, MADISON - New York Medical College; YANG, NAN - General Nutraceutical Technology, Llc; TIWARI, RAJ - New York Medical College; GELIEBTER, JAN - New York Medical College; Maleki, Soheila; LI, XIU-MIN - New York Medical College

Submitted to: Allergology International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/29/2025
Publication Date: 2/10/2026
Citation: Maskey, A., Caranzza, M., Kopulos, D., Spears, M., Yang, N., Tiwari, R., Geliebter, J., Maleki, S.J., Li, X. 2026. Cross-IgE sensitization correlates with cross-anaphylaxis among peanut and multiple tree nuts in a murine model. Allergology International. 6-2025. https://doi.org/10.3389/falgy.2025.1720870.
DOI: https://doi.org/10.3389/falgy.2025.1720870

Interpretive Summary: Food allergies have become more common, and people with multiple food allergies often have more serious reactions. In this study, we wanted to understand how eating peanuts and certain tree nuts, like walnuts and cashews, might lead to allergic reactions with other types of tree nuts, even if the person has never eaten those before. To do this, we experimented with mice, exposing them to a mix of peanuts, walnuts, and cashews to see how their immune systems reacted. We then tested how they responded when given different tree nuts, including almonds, pecans, and others. We paid special attention to symptoms of severe allergic reactions, known as anaphylaxis. Our results showed that even without previous exposure to the other nuts, the mice had allergic reactions due to their initial exposure to peanuts, walnuts, and cashews. We found strong links between the levels of specific allergy-causing antibodies and the severity of the reactions. This suggests that if someone is allergic to peanuts, walnuts, or cashews, they might also react to other nuts. Overall, our findings indicate that allergens from peanuts, walnuts, and cashews can lead to serious allergic symptoms with a range of other tree nuts. This information could be important for healthcare providers when helping people with multiple food allergies.

Technical Abstract: Background: Food allergies (FA) have increased in incidence. Those with multiple FA (MFA) have an increased rate and severity of allergic reactions. We sought to mimic clinical sensitization of peanut/ tree nut (PN/TN) MFA of common allergens, PN, walnut (WN), and cashew (CSH) cross-reactivity with eight other TNs. Methods: Sensitization of C3H/HeJ mice with PN, WN, and CSH mixture intraperitoneally (i.p.) for primed and cross-reactive IgE levels was compared to naïve. Intragastric (i.g.) challenges with primed, PN, WN, CSH, and unprimed allergens, almond (ALM), pecan (PCN), pistachio, hazelnut, Brazil nut, pinenut (PINE), macadamia (MCDM) and coconut were performed and anaphylaxis symptoms ascertained. Correlation of primed IgE levels and symptoms scores with primed and unprimed allergens were conducted. Results: MFA was apparent following PN, WN, and CSH sensitization against cross-reactive TNs, despite never exposed, with elevated specific IgE (sIgE) of primed (p<0.0001) and unprimed allergens (p<0.0001). Cross-reactivity was confirmed with anaphylaxis symptoms upon primed and unprimed nut challenges (p<0.0001 vs Naïve, all). Strong correlations among sIgE levels and anaphylaxis for primed and unprimed allergens were observed (r>0.7, p<0.0001). Correlation of sIgE levels and anaphylaxis between primed nut allergens were strongly positive (r>0.8, p <0.0001). Correlation of each primed to unprimed allergen showed striking cross-reactivity between PN and MCDM and PINE; WN and MCDM, ALM, and PINE; and CSH and ALM, PCN, and PINE.