Caleb Kelly

Sesame allergy : a growing food allergy of global proportions?

OBJECTIVE To present an up-to-date synopsis on the global prevalence, natural history, nature of allergens, and immune mechanisms of sesame allergy. DATA SOURCES We performed a literature search using the PubMed database. We obtained information on regulatory issues from the Web pages of respective agencies. STUDY SELECTION The PubMed search was performed using the algorithm sesame AND allergy. Date restriction was not used, and only articles in English were considered. The articles obtained were screened for additional references to work not obtained in the initial search. Each article was analyzed, and a pooled source of published information was generated. RESULTS Evidence was found for increased reporting of sesame allergy during the past 5 decades, with reports mostly from developed countries. Clinically, most sesame allergy was presented in at least 2 major forms: (1) immediate hypersensitivity, often expressed as systemic anaphylaxis, associated with positive skin prick test and/or IgE antibody test results to sesame proteins with some cross-reactivity with other foods, and (2) delayed hypersensitivity to lignin-like compounds in sesame oil clinically expressed as contact allergic dermatitis. There were a few cases of immediate hypersensitivity to sesame with negative skin prick test and/or IgE antibody test results that were confirmed by oral challenge tests. CONCLUSIONS Sesame allergy is a significant, serious, and growing problem. Evidence exists of the ability of protein and oil components of sesame to trigger immediate hypersensitivity via IgE antibody and delayed hypersensitivity via cell-mediated immune responses, respectively.

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

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.

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

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.

Sex Disparity in Food Allergy: Evidence from the PubMed Database

Food allergies are potentially fatal immune-mediated disorders that are growing globally. The relationship between sex and food allergy remains incompletely understood. Here we tested the hypothesis that, should sex influence the clinical response to food allergens, this would be reflected by a sex disparity in published studies of food allergy. We performed a systematic search of the PubMed literature for IgE-mediated allergy to 11 allergenic foods of international regulatory importance. No date restriction was used and only articles in English were considered. Of the 4744 articles retrieved, 591 met the inclusion criteria representing 17528 subjects with food allergies. Whereas among children with food allergies, 64.35% were males and 35.65% were females (male/female ratio, 1.80), among adults 34.82% were males and 65.18% were females (male/female ratio, 0.53). Consequently, these data argue that there is need for further investigation to define the role of sex in the pathogenesis of food allergy.

Hazelnut Allergy: Evidence that Hazelnut Can Directly Elicit Specific IgE Antibody Response via Activating Type 2 Cytokines in Mice

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.

Optimization, Comparison, and Application of Colorimetric vs. Chemiluminescence Based Indirect Sandwich ELISA for Measurement of Human IL‐23

Abstract Currently, there is neither a published ELISA method nor it is clear whether chemiluminescence substrates would provide better sensitivity vs. colorimetric substrates for measuring human IL‐23–a recently described Type‐1 immunity associated cytokine. Initially, we optimized a colorimetric ELISA using p‐nitro‐phenyl phosphate substrate. Subsequently, we compared it with chemiluminescence substrates that provided ∼5‐fold enhanced sensitivity (mean sensitivity; 26.3 pg/mL vs. colorimetric assay, 131 pg/mL; p<0.01). Both methods were reliable, with <10% inter‐ and intra‐assay variations. We then found that the chemiluminescence method was useful in situations where human IL‐23 was not readily measurable by a colorimetric method.