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

Abstract

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.

Apigenin Attenuates the Allergic Reactions by Competitively Binding to ER With Estradiol

“…Food allergy refers to a hypersensitivity disorder in which the immune system abnormally reacts to non-infectious environmental substances ( Galli et al., 2008 ), often induces a series of allergic disease complications, such as urticaria, asthma, and diarrhea, which could seriously affect quality of life ( Ballegaard et al., 2019 ). It has been recognized by the World Health Organization (WHO) as a major global food safety issue ( Wang et al., 2019 ) and seriously affected about as many as 10% of children globally ( Abrams et al., 2020 ).…”

Gluten tolerance prevents oral sensitization with enzymatic or acid hydrolyzed gluten: A study in Brown Norway rats

“…The possible influence of tolerance to wheat was not discussed in that paper. A study by Ballegaard [23] sheds light on the influence of tolerance on sensitization via the skin. BN rats that were either naïve or tolerant to gluten were sensitized on slightly damaged skin with G or AHG.…”

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

“…Using a skin sensitization method, Ballegaard et al (2019) studied the allergenicity of native gluten vs. AHG in wheat-tolerant mice fed with wheat diet vs. naïve mice that had been on a wheat-free diet [48]. They found that in naïve rats that were not wheat-tolerant, both glutens elicited allergenic responses.…”

“…However, animal models can be used to study this critical issue. Currently, most animal models have used intraperitoneal (IP) injections in sensitization with the exception of one mouse and one rat model, where skin sensitization was used, and one rat model, where oral sensitization was studied [38,47,48] (Table 5). The mouse models used injections to elicit anaphylaxis.…”

“…However, humans are not exposed to wheat allergens along with alum adjuvant. In that sense, adjuvant-free models, such as skin sensitization models, reported for mouse and rats are desirable because data interpretation of the intrinsic allergenicity of wheat proteins becomes easier [38,48]. There are a number of adjuvant-free mouse models reported in the literature for tree nut, milk, sesame, and shellfish allergies [39,40,41,42,43,49,50].…”