Allergic and Anaphylactic Response to Sesame Seeds in Mice: Identification of Ses i 3 and Basic Subunit of 11s Globulins as Allergens

Self Cite

Background: Clinically it is recognized that tree nut allergies such as hazelnut allergy are not usually outgrown. Specific mechanisms underlying the persistence of such food allergies are incompletely understood. Here we studied the natural history and the long-term immune and clinical characteristics of hazelnut allergy in an adjuvant-free mouse model. Methods: BALB/c mice were sensitized to hazelnut protein using a transdermal sensitization protocol that does not use adjuvant. After establishing sensitization, exposure to hazelnut was withdrawn for 3, 5 or 8 months. The fate of circulating IgE antibodies was monitored. Subsequently, mice were given booster exposures and examined for memory IgE antibody and spleen cell IL-4 responses. Clinical characteristics and hypothermia responses upon oral allergen challenge were studied. Results: Upon allergen withdrawal, circulating hazelnut-specific IgE antibody levels began to drop. Nevertheless, IgE responses once established remained at significantly high levels for up to 8 months (the last time point studied) despite withdrawal of allergen exposure. Memory IgE responses to booster exposures were robust after 3, 5 or 8 months of allergen withdrawal. Furthermore, significant clinical reactivity to oral hazelnut challenge, and hypothermia responses were demonstrable at each of these time points. Long-lasting spleen cell memory IL-4 responses to hazelnut were detectable in these mice explaining the mechanism of sustenance of IgE responses and clinical sensitization. Conclusions: Hazelnut allergy once established persists for long periods, despite withdrawal of allergen exposure, due to long-lasting, memory IgE and IL-4 responses.

Section: Discussionsupporting

confidence: 53%

Long-Term Characteristics of Hazelnut Allergy in an Adjuvant-Free Mouse Model

Gonipeta

Parvataneni

Paruchuri

et al. 2010

Self Cite

“…However, few recent studies, including ours, have shown that transdermal exposure to other allergenic food proteins, e.g. ovalbumin, hazelnut and sesame seed, can result in both immune activation and clinical sensitization for immediate hypersensitivity reaction including systemic anaphylaxis [18, 19, 22]. Strid et al [23 ]demonstrated a delayed hypersensitivity response to peanut via skin exposure in the ear using the tape-stripping method.…”

Section: Discussionmentioning

confidence: 96%

“…We chose the BALB/c strain of mice to develop a cashew nut allergy model because: (i) this strain has earlier been used in allergy studies by many in the field including us; however, whether they develop allergic responses to cashew nut was unknown [18,19,20,21], and (ii) many gene knockout mice are available on BALB/c genetic background, and therefore it will be valuable for further mechanistic studies on cashew nut allergy.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, mouse models of peanut allergy and cow’s milk allergy are based on using adjuvant such as cholera toxin and alum [16,24,25,26]. In contrast, mouse models of hazelnut allergy and sesame seed allergy have used a novel adjuvant-free method involving exposure to food proteins via the skin [18, 19, 22]. Here, we demonstrate for the first time that it is possible to use the adjuvant-free approach to develop a mouse model of cashew nut allergy.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Development of an Adjuvant-Free Cashew Nut Allergy Mouse Model

Parvataneni¹,

Gonipeta²,

Tempelman

et al. 2009

Self Cite

Background: Cashew nut allergy is an emerging food allergy with a high risk of systemic anaphylaxis. Currently, an adjuvant-free animal model to study cashew nut allergy is not available. Methods: BALB/c mice were exposed to cashew nut protein using a transdermal sensitization protocol that does not use adjuvant. Systemic IgE antibody response, systemic anaphylaxis to oral challenge and allergen-driven, spleen-cell, type-2 cytokine responses were studied. Results: Transdermal exposure to cashew nut resulted in a significant dose-dependent allergic response. Oral challenge of sensitized mice with cashew resulted in severe signs of systemic anaphylaxis and a significant hypothermia. Spleen cell culture with cashew nut protein resulted in allergen-driven IL-4, IL-5 and IL-13 responses only in sensitized but not in saline control mice. Conclusions: These data demonstrate that (i) transdermal exposure to cashew nut protein elicits a robust IgE response leading to clinical sensitization of mice for systemic anaphylaxis to oral cashew nut challenge; (ii) cashew nut is a potent activator of type-2 cytokines, thus explaining the mechanism of cashew allergy, and (iii) this mouse model may be useful for further basic and preclinical studies on cashew nut allergy.

“…Although most food allergies typically start in infancy and tend to be outgrown before adulthood, some food allergies such as tree nut allergies are considered to last for a lifetime as chances of outgrowing such sensitizations are minimal [1]. Furthermore, peanuts, tree nuts (such as hazelnuts and walnuts) and sesame seeds are the major food types that often cause systemic anaphylaxis with fatal or near-fatal consequences [1, 2, 5, 6]. Thus, tree nut allergy is a clinically significant and very serious immune-mediated disorder that remains incompletely understood at present.…”

Section: Introductionmentioning

confidence: 99%

An Adjuvant-Free Mouse Model of Tree Nut Allergy Using Hazelnut as a Model Tree Nut

Birmingham¹,

Parvataneni²,

Hassan³

et al. 2007

Self Cite

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.