A Mouse Model of Anaphylaxis and Atopic Dermatitis to Salt-Soluble Wheat Protein Extract

Jin, Yining; Ebaugh, Sarah; Martens, Anna; Gao, Haokao; Olson, Eric; Ng, P. K. W.; Gangur, Venu

doi:10.1159/000479386

Cited by 16 publications

(54 citation statements)

References 30 publications

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“…Temperature was measured every 5 to 15 minutes with a rectal probe. Previous publications have shown that the development of hypothermia correlates with mast cell degranulation in murine IgE-mediated anaphylaxis by demonstrating (1) a correlation between degree of hypothermia and mouse mast cell protease 1 (MMCP-1) responses; [26][27][28] (2) the failure of mast cell-deficient mice to develop hypothermia in response to cross-linking of IgE; 6 and (3) the importance of histamine in IgE-mediated anaphylaxis. 6…”

Section: Detection Of Systemic Anaphylaxismentioning

confidence: 99%

Rapid desensitization of humanized mice with anti-human FcεRIα monoclonal antibodies

Khodoun

Morris

Angerman

et al. 2020

Journal of Allergy and Clinical Immunology

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Background: Anaphylaxis is classically mediated by allergen cross-linking of IgE bound to the a chain of FcεRI, the mast cell/basophil high affinity IgE receptor. Allergen cross-linking of the IgE/FcεRI complex activates these cells, inducing release of disease-causing mediators, cytokines, and enzymes. We previously demonstrated that IgE-mediated anaphylaxis could be safely prevented in wild-type BALB/c mice by rapid desensitization with anti-mouse FcεRIa mAb. Objective: This study sought to use humanized mice to extend these results to humans. Methods: We actively immunized huFcεRIa/F709 mice, which express human (hu) instead of mouse FcεRIa and a mutant IL-4 receptor that lacks inhibitory function. We passively immunized huFcεRIa mice, as well as human cord blood-reconstituted reNSGS mice, which are immune-deficient, produce mast cellstimulating human cytokines, and develop numerous human mast cells. For desensitization, we used anti-huFcεRIa mAbs that bind FcεRIa regardless of its association with IgE (noncompeting mAbs), and/or mAbs that compete with IgE for huFcεRIa binding (competing mAbs). Anaphylaxis was induced by intravenous injection of antigen or anti-huIgE mAb. Results: Anti-huFcεRIa mAb rapid desensitization was safer and more effective than allergen rapid desensitization and suppressed anaphylaxis more rapidly than omalizumab or ligelizumab. Rapid desensitization of na€ ıve, IgE-sensitized huFcεRIa mice and huFcεRIa/F709 mice that were egg-allergic with anti-FcεRIa mAbs safely removed >98% of IgE from peritoneal mast cells and completely suppressed IgE-mediated anaphylaxis. Rapid desensitization of reNSGS mice with anti-FcεRIa mAbs also safely removed 98% of mast cell IgE and prevented IgE-mediated anaphylaxis. Conclusions: Rapid desensitization with anti-FcεRIa mAbs may be a safe, effective, and practical way to prevent IgE-mediated anaphylaxis.

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Section: Detection Of Systemic Anaphylaxismentioning

confidence: 99%

Rapid desensitization of humanized mice with anti-human FcεRIα monoclonal antibodies

Khodoun

Morris

Angerman

et al. 2020

Journal of Allergy and Clinical Immunology

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“…As discussed in the introduction, salt-soluble wheat proteins (SSWPs) are also important allergens in wheat allergic humans [44]. Therefore, Jin et al (2017) tested whether SSWPs can elicit allergic disease in Balb/c mice similar to humans (Table 2 and Table 4) [45]. They found that: (i) SSWP elicits robust IgE responses and sensitization, and mice show anaphylaxis when challenged; (ii) they showed for the first time that in this mouse model, anaphylaxis is linked to IgE-mediated mucosal mast cell degranulation [45,46]; and (iii) interestingly, some of the wheat allergic mice (but not all) developed atopic dermatitis lesions on the face, showing extensive mast cell degranulation and elevated levels of pro-inflammatory and allergic chemokines and cytokines (Table 2 and Table 4).…”

Section: Insights In To the Molecular Mechanisms Of Wheat Allergenmentioning

confidence: 99%

“…There are conflicting reports of whether B10.A does or does not develop an IgE response to gliadins [27,28]. In particular, Balb/c mice show immune responses that are remarkably similar to that of wheat allergic humans [30,45]. Interestingly, C3H/Hej mice, which are popular peanut allergy models, do not develop a gliadin allergy, suggesting the possibility of genetic resistance [30].…”

Section: Insights In To the Molecular Mechanisms Of Wheat Allergenmentioning

confidence: 99%

“…As noted earlier, both the rat and most mouse models, except Jin et al (2017), who used salt-soluble wheat protein extract) used gliadins either as a gluten extract or purified gliadin protein [45]. However, human exposure to wheat via food or in occupational settings involves natural exposure to all four groups of wheat proteins at the same time.…”

Section: Insights In To the Molecular Mechanisms Of Wheat Allergenmentioning

confidence: 99%

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Advances in Molecular Mechanisms of Wheat Allergenicity in Animal Models: A Comprehensive Review

Jin

Acharya

et al. 2019

Molecules

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The prevalence of wheat allergy has reached significant levels in many countries. Therefore, wheat is a major global food safety and public health issue. Animal models serve as critical tools to advance the understanding of the mechanisms of wheat allergenicity to develop preventive and control methods. A comprehensive review on the molecular mechanisms of wheat allergenicity using animal models is unavailable at present. There were two major objectives of this study: To identify the lessons that animal models have taught us regarding the molecular mechanisms of wheat allergenicity and to identify the strengths, challenges, and future prospects of animal models in basic and applied wheat allergy research. Using the PubMed and Google Scholar databases, we retrieved and critically analyzed the relevant articles and excluded celiac disease and non-celiac gluten sensitivity. Our analysis shows that animal models can provide insight into the IgE epitope structure of wheat allergens, effects of detergents and other chemicals on wheat allergenicity, and the role of genetics, microbiome, and food processing in wheat allergy. Although animal models have inherent limitations, they are critical to advance knowledge on the molecular mechanisms of wheat allergenicity. They can also serve as highly useful pre-clinical testing tools to develop safer genetically modified wheat, hypoallergenic wheat products, novel pharmaceuticals, and vaccines.

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“…Improved and novel models to study the disease will also contribute to further developing alternative treatment [46]. …”

Section: Atopic Dermatitismentioning

confidence: 99%

Recent Advances in Experimental Allergy

Adams

Gunten

2018

Int Arch Allergy Immunol

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Atopic disorders are on the rise and pose a great burden on society. A better understanding of the underlying mechanisms is required for the development of improved or novel therapeutic strategies. Here we aim to highlight recent advances in experimental allergy, with a particular focus on proposed treatment alternatives for airway disorders, atopic dermatitis, and food allergy. Furthermore, we discuss recent work focusing on molecular and cellular mechanisms that might offer candidates for future preventive or therapeutic intervention.

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A Mouse Model of Anaphylaxis and Atopic Dermatitis to Salt-Soluble Wheat Protein Extract

Cited by 16 publications

References 30 publications

Rapid desensitization of humanized mice with anti-human FcεRIα monoclonal antibodies

Rapid desensitization of humanized mice with anti-human FcεRIα monoclonal antibodies

Advances in Molecular Mechanisms of Wheat Allergenicity in Animal Models: A Comprehensive Review

Recent Advances in Experimental Allergy

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