Murine model of cross-IgE sensitization and cross-anaphylactic reactions among multiple group food allergens

Authors: MUSA, IBRAHIM - New York Medical College; ARDALANI, FARIBA - New York Medical College; YANG, NAN - General Nutraceutical Technology, Llc; Maleki, Soheila; LI, XIU-MIN - New York Medical College

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/5/2024
Publication Date: 1/7/2025
Citation: Musa, I., Ardalani, F., Yang, N., Maleki, S.J., Li, X. 2025. Murine model of cross-IgE sensitization and cross-anaphylactic reactions among multiple group food allergens. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2024.1497368.
DOI: https://doi.org/10.3389/fimmu.2024.1497368

Interpretive Summary: Approximately 32 million people in the US suffer from food allergies. Some food groups, such as legumes, peanuts, tree nuts as one group and fish, and shellfish as another, have a high risk of cross-reactivity. This means that if you have allergy to one food within the group, you are highly likely to be allergic to other foods in that group. However, a good mouse model of multiple food group allergic cross-reactivity is not available. We sought to develop a murine model that can be used to investigate novel therapeutics for the simultaneous treatment of multiple food allergies. A specific strain of mice ( named C3H/HeJ) were sensitized once a week for three weeks with a mixture of 500µg of protein from peanut, cashew, walnut, shrimp, cod, and 2 mg Alum. The control group consisted of non sensitized or allergic mice. Immunoglobulin E (IgE) antibody levels against the allergens and their cross-reactive allergens within the same group were measured by after sensitization. In weeks 4 and 5, the mice were given intragastric challenges with 200mg/mouse of each food: peanut, chickpea, lentil, cashew, almond, pistachio, hazelnut, brazil nut, walnut, pecan, shrimp, lobster, cod, salmon, and mackerel. After each challenge, anaphylactic symptoms such as temperatures, and plasma histamine levels were measured. There was a significant elevation of IgE against sensitized antigens (peanut cashew, walnut, shrimp, and cod) as well as cross-reactive allergens used for oral food challenge from legumes including peanut, chickpea, and lentil, as well as tree nuts such as cashew, almond, pistachio, hazelnut, brazil nut, walnut, and pecan. Furthermore, there was a significant increase in crustaceans such as shrimp, lobster and fish like cod, salmon, and mackerel . Significantly increased anaphylactic symptom scores, such as decreased temperature, and increased plasma histamine were observed compared to the untreated following each challenge with sensitized foods and the foods in the same group. We generated a comprehensive murine model of IgE-mediated multi-food group allergic and cross-reactive anaphylaxis. This will provide an essential tool for testing and developing novel therapies for cross-reactivity in multiple food allergies.

Technical Abstract: Approximately 32 million people in the US suffer from food allergies. Some food groups, such as legumes, peanuts, tree nuts, fish, and shellfish, have a high risk of cross-reactivity. However, the murine model of multiple food group cross-reactivity is limited. We sought to develop a murine model that can be used to investigate novel therapeutics for the treatment of multiple food allergies. C3H/HeJ mice were sensitized intraperitoneally (i.p.) once a week for three weeks with a mixture of 500µg of protein from peanut, cashew, walnut, shrimp, cod, and 2 mg Alum. The control group consisted of naïve mice. IgE levels against the sensitized allergens and their cross-reactive allergens were measured by ELISA at baseline and 3 weeks after sensitization. In weeks 4 and 5, the mice were given intragastric challenges with 200mg/mouse of each food: peanut, chickpea, lentil, cashew, almond, pistachio, hazelnut, brazil nut, walnut, pecan, shrimp, lobster, cod, salmon, and mackerel. After each challenge, anaphylactic symptoms, and rectal temperatures, and plasma histamine were measured. There was a significant elevation of IgE against sensitized antigens (peanut cashew, walnut, shrimp, and cod) as well as cross-reactive allergens used for oral food challenge from legumes including peanut, chickpea, and lentil, as well as tree nuts such as cashew, almond, pistachio, hazelnut, brazil nut, walnut, and pecan. Furthermore, there was a significant increase in crustaceans such as shrimp, lobster and fish like cod, salmon, and mackerel (p<0.01). Consistently, significantly increased anaphylactic symptom scores (p<0.05), decreased rectaltemperature (p<0.001), and increased plasma histamine (p<0.05) compared to the naïve mice occurred following each challenge with sensitized foods and unsensitized, but cross-reactive foods. We generated a comprehensive murine model of IgE-mediated multiple food groups of cross-reactive anaphylaxes. This will provide an essential tool for developing novel therapies for cross-reactivity in multiple food allergies.