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Cashew, hazelnut, and walnut allergen proteins represent a group of highly stable seed storage and defense proteins that are the primary drivers of tree nut-induced IgE-mediated hypersensitivity. These proteins are categorized into several families, most notably the 2S albumins (e.g., Ana o 3, Cor a 14, Jug r 1), 7S globulins or vicilins (e.g., Ana o 1, Cor a 11, Jug r 2), and 11S globulins or legumins (e.g., Ana o 2, Cor a 9, Jug r 4), which are known for their resistance to heat and enzymatic degradation (WHO/IUIS Allergen Nomenclature, 2024). In sensitized individuals, exposure to these allergens triggers the cross-linking of IgE on the surface of mast cells and basophils, resulting in the rapid release of histamine and other inflammatory mediators that can lead to anaphylaxis (NIH/NIAID, 2024). From a therapeutic perspective, these proteins are the targets of allergen-specific immunotherapy (AIT), which aims to reprogram the immune system toward tolerance by gradual exposure. Modern pharmacological approaches also include the use of biologics like omalizumab to increase the threshold of allergen reactivity and improve the safety profile of desensitization protocols (FDA, 2024). Additionally, component-resolved diagnostics (CRD) utilize these specific proteins to improve the accuracy of allergy testing and predict the risk of severe reactions (UniProt Consortium, 2024).
Induction of immunological tolerance through allergen-specific immunotherapy (AIT) which shifts the immune response from Th2-biased to Th1/Treg-mediated, and sequestration of free IgE by monoclonal antibodies to prevent mast cell degranulation.
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