Background: Tree nut allergy, a major group of food allergy, is often linked to fatal or near-fatal systemic anaphylaxis. Currently, an adjuvant-free mouse model to study tree nut hypersensitivity is unavailable. Here we tested the hypothesis that transdermal exposure to hazelnut, a model tree nut, without the use of an adjuvant is sufficient to sensitize mice for immediate hypersensitivity reaction to oral hazelnut challenge. Methods: BALB/c mice were repeatedly exposed to hazelnut protein via the transdermal route and systemic allergic and anaphylactic responses were studied. Results: Transdermal exposure to hazelnut protein elicited robust systemic IgE response in a dose-dependent manner with immunological memory. Oral challenge of transdermally sensitized mice with hazelnut protein resulted in immediate (30 min after the challenge) clinical signs of systemic anaphylaxis as measured by significant clinical scores and drop in rectal temperature. Clinical hypersensitivity reaction was associated with severe pathological changes in the small intestine. Hazelnut-allergic but not control mice exhibited in vivo activation of GATA-3 and hazelnut-driven recall IL-4, IL-5 and IL-13 response by splenocytes, thus elucidating the underlying mechanism of hazelnut allergy development in this model. Conclusions: These data suggest that (1) transdermal exposure to hazelnut protein is sufficient to activate the key immune pathways necessary for sensitizing mice for clinical immediate hypersensitivity reactions and (2) this mouse model may be useful for further basic and applied studies on tree nut allergy, especially because it does not depend on an adjuvant for eliciting immediate hypersensitivity reactions to nut protein.

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Background: Allergy to sesame seeds is an emerging food allergy of a serious nature due to a high risk of systemic anaphylaxis. Although a mouse model to study sesame anaphylaxis is desirable, currently it is not available. Here, using a transdermal exposure model system, we tested the hypothesis that sesame seed elicits IL-4-associated IgE antibody response with consequent clinical sensitization in mice. Methods: Groups of BALB/c mice were exposed to sesame seed extract or saline or a control food (vanilla bean extract) by transdermal applications. Systemic IgE, IgG1 and IgG2a antibody responses were examined using preoptimized ELISA. Type 2 and type 1 cytokine responses were evaluated by ex vivo antigen-mediated activation of spleen cells. Clinical response to oral sesame challenge was studied. Western blot and N-terminal amino acid sequence analyses were performed to identify the sesame allergens. Results: Transdermal exposure to sesame elicited robust IgE and IgG1 but very little IgG2a antibody responses. IgE response to transdermal exposure in two high-IgE responder mice strains with disparate MHC confirmed the intrinsic allergenicity of sesame seed. Transdermal sensitization was associated with activation of IL-4 but not IFN-γ. Furthermore, oral exposure to sesame resulted in clinical signs of systemic anaphylaxis. Western blot and sequence analysis identified four allergens including Ses i 3 and the basic subunit of 11s globulins. Conclusion: These data argue that transdermal exposure to sesame seed can result in IL-4 activation, IgE response and clinical sensitization for systemic anaphylaxis.

Background: Hazelnut is one of the major tree nuts that causes potentially fatal food allergy, with underlying mechanisms that are unclear at present. One suggestion is that hazelnut allergy results from immune crossreactivity of IgE antibodies produced against certain aeroallergens. We tested the hypothesis that hazelnut is intrinsically capable of eliciting an allergic response using a mouse model. Methods: Groups of mice were injected intraperitoneally with hazelnut/filbert protein extract with or without alum as an adjuvant, and hazelnut-specific antibody (IgE, IgG1) responses were examined using optimized enzyme-linked immunosorbent assay. Hazelnut-specific type 2 and type 1 cytokine responses were evaluated by ex vivo antigen-mediated activation of spleen cells. Results: Hazelnut elicited robust IgE and IgG1 antibody responses. Timecourse and dose-response analyses further provided evidence for memory type 2-dependent antibody responses to hazelnuts. Hazelnut-specific IgE response in two strains of mice with different MHC haplotypes and IgE response to hazelnut without the use of alum adjuvant asserted that hazelnut is intrinsically an allergenic food. The type 2 cytokine analyses revealed that hazelnut sensitization results from activation of IL-4 and IL-5, thus providing a mechanistic basis for hazelnut-specific IgE response. Conclusion: Our data argue that hazelnut – a widely consumed food – is intrinsically an allergenic food capable of directly eliciting hazelnut-binding specific IgE antibodies viaactivation of type 2 cytokines in mice.

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