Sensitization to acid‐hydrolyzed wheat protein by transdermal administration to <scp>BALB</scp>/c mice, and comparison with gluten

Adachi, Reiko; Nakamura, Ryosuke; Sakai, Shinobu; Fukutomi, Yuma; Teshima, Reiko

doi:10.1111/all.12018

Cited by 41 publications

(47 citation statements)

References 22 publications

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“…Different food allergens have been used in the animal models such as peanut, hazelnut, and cashew nut protein extracts, and hen’s egg ovalbumin (OVA), resulting in elevated levels of antigen-specific IgE [24-27]. Few animal studies have investigated allergic reactions towards hydrolysed wheat products [28-30]. In this study, the aim was to establish an animal model for food allergy skin sensitisation and investigate the sensitising capacity of an unmodified and an acid-hydrolysed gluten product in naïve versus tolerant Brown Norway (BN) rats.…”

Section: Introductionmentioning

confidence: 99%

An Animal Model for Wheat Allergy Skin Sensitisation: A Comparative Study in Naive versus Tolerant Brown Norway Rats

Ballegaard

Madsen

Bøgh³

2018

Int Arch Allergy Immunol

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Background: Allergic sensitisation to foods may occur in infancy without prior oral exposure to the offending food, leading to the assumption that food allergy sensitisation may occur through the skin. Concerns have been raised regarding the safety of use of personal care products containing hydrolysed wheat proteins, since these products have been shown to induce allergy through the skin, and even cause an abrogation of an already established oral tolerance. Objective: To establish an animal model for food allergy skin sensitisation and compare the sensitising capacity of an unmodified and an acid-hydrolysed gluten product via slightly damaged skin in naïve versus tolerant rats. Methods: Gluten products were applied on the slightly damaged skin of naïve or tolerant Brown Norway (BN) rats without adjuvant 3 times per week for 3 or 5 consecutive weeks. The effect of the skin applications was evaluated by means of different ELISAs and immunoblotting. Results: A robust animal model was developed for food allergy skin sensitisation. In naïve rats, both gluten products were able to induce a statistically significant level of specific antibodies and sensitise through the skin, but in the wheat-tolerant rats, only the acid-hydrolysed gluten was able to sensitise through the skin, albeit at a level much lower than in the naïve rats. Results showed that new epitopes had been developed as a result of acid hydrolysis but original epitopes were maintained. This may explain why only the acid-hydrolysed gluten could induce specific antibody responses in the tolerant animals. Conclusions: This study showed that it is possible to sensitise BN rats through slightly damaged skin, and that the sensitising capacity is heavily influenced by the tolerance status of their immune system and the degree of modification of the wheat products.

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Section: Introductionmentioning

confidence: 99%

An Animal Model for Wheat Allergy Skin Sensitisation: A Comparative Study in Naive versus Tolerant Brown Norway Rats

Ballegaard

Madsen

Bøgh³

2018

Int Arch Allergy Immunol

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“…They studied IgE responses, intestinal permeability, intestinal anaphylaxis, and gut histamine release. Adachi et al [14] reported a transdermal sensitization model using acid-hydrolyzed gluten [14]. They studied IgE responses and anaphylaxis upon IP challenge.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to the previous models, our model differs significantly in a number of ways. Firstly, we used SSWP extract for the first time; previous models used the alcohol-soluble proteins or purified LTP [10,11,12,13,14]. Secondly, we quantified the HSRs; among the previous models, only Adachi et al [14] reported the utility of HSR for gluten sensitization [14].…”

Section: Discussionmentioning

confidence: 99%

“…Firstly, we used SSWP extract for the first time; previous models used the alcohol-soluble proteins or purified LTP [10,11,12,13,14]. Secondly, we quantified the HSRs; among the previous models, only Adachi et al [14] reported the utility of HSR for gluten sensitization [14]. Thirdly, we studied mucosal mast cell degranulation by quantifying the elevation of plasma levels of mMCP-1 postchallenge; notably this readout is a specific biomarker of IgE- (but not IgG1-)mediated anaphylaxis in mice [21].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, wheat contains not only salt-soluble allergens but also alcohol-soluble and acid-soluble protein allergens that can trigger IgE-mediated reactions in humans [8,1,2,3]. Previously, elegant mouse models of wheat hypersensitivity to alcohol-soluble wheat gluten proteins were developed [10,11,12,13,14]. One study evaluated the immune response to purified lipid transfer protein (LTP) in mice [11].…”

Section: Introductionmentioning

confidence: 99%

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

Jin

Ebaugh

Martens

et al. 2017

Int Arch Allergy Immunol

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Background: Wheat allergy and other immune-mediated disorders triggered by wheat proteins are growing at an alarming rate for reasons not well understood. A mouse model to study hypersensitivity responses to salt-soluble wheat protein (SSWP) extract is currently unavailable. Here we tested the hypothesis that SSWP extract from wheat will induce sensitization as well as allergic disease in mice. Methods: Female BALB/cJ mice were weaned onto a plant protein-free diet. The mice were injected a total of 4 times with an SSWP (0.01 mg/mouse) fraction extracted from durum wheat along with alum as an adjuvant. Blood was collected biweekly and SSWP-specific IgE (SIgE) and total IgE (TIgE) levels were measured using ELISA. Systemic anaphylaxis upon intraperitoneal injection with SSWP was quantified by hypothermia shock response (HSR). Mucosal mast cell degranulation was measured by the elevation of mMCP-1 in the blood. The mice were monitored for dermatitis. Skin tissues were used in histopathology and for measuring cytokine/chemokine/adhesion molecule levels using a protein microarray system. Results: Injection with SSWP resulted in time-dependent SIgE antibody responses associated with the elevation of TIgE concentration. Challenge with SSWP elicited severe HSR that correlated with a significant elevation of plasma mMCP-1 levels. Sensitized mice developed facial dermatitis associated with mast cell degranulation. Lesions expressed significant elevation of Th2/Th17/Th1 cytokines and chemokines and E-selectin adhesion molecule. Conclusion: Here we report a mouse model of anaphylaxis and atopic dermatitis to SSWP extract that may be used for further basic and applied research on wheat allergy.

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Determining Food Allergens by Skin Sensitization in Mice

et al. 2018

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A food allergy is a chronic inflammatory disease against dietary antigens with high prevalence in industrialized countries. Because there is currently no cure for food allergies, avoiding the allergen is crucial for the prevention of an allergic reaction. Therefore, a further understanding of the pathogenesis and risk factors that augment the sensitization to food allergens is required. We have previously developed a food allergy mouse model using transdermal sensitization, which influences the susceptibility to food allergies. In this model, mice sensitized with partially hydrolyzed wheat protein (HWP) successfully resembled the major features of HWP-sensitized and wheat allergy-induced patients. In this article, we describe transdermal sensitization of food allergens and induction of immediate-type food allergies in mice. The methodology detailed here was mainly adapted from an original work by Adachi and colleagues with some modifications to the dressing methods to reduce stress. © 2018 by John Wiley & Sons, Inc.

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Sensitization to acid‐hydrolyzed wheat protein by transdermal administration to BALB/c mice, and comparison with gluten

Abstract: Transdermal exposure to HWP1 is sufficient to activate key immune pathways necessary for sensitizing mice for immediate hypersensitivity reactions. This study shows that HWP has a sensitizing potential as well as gluten, whereas its allergenicity may be different from that of gluten.

Cited by 41 publications

References 22 publications

An Animal Model for Wheat Allergy Skin Sensitisation: A Comparative Study in Naive versus Tolerant Brown Norway Rats

An Animal Model for Wheat Allergy Skin Sensitisation: A Comparative Study in Naive versus Tolerant Brown Norway Rats

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

Determining Food Allergens by Skin Sensitization in Mice

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