Acid Hydrolysis of Gluten Enhances the Skin Sensitizing Potential and Drives Diversification of IgE Reactivity to Unmodified Gluten Proteins

Abstract

Scope: Personal care products containing hydrolyzed gluten have been linked to spontaneous sensitization through the skin, however the impact of the hydrolysate characteristics on the sensitizing capacity is generally unknown. Methods and Results: The physicochemical properties of five different wheat-derived gluten products (one unmodified, one enzyme hydrolyzed, and three acid hydrolyzed) are investigated, and the skin sensitizing capacity is determined in allergy-prone Brown Norway rats. Acid hydrolyzed gluten products exhibited the strongest intrinsic sensitizing capacity via the skin. All hydrolyzed gluten products induced cross-reactivity to unmodified gluten in the absence of oral tolerance to wheat, but were unable to break tolerance in animals on a wheat-containing diet. Still, the degree of deamidation in acid hydrolyzed products is associated with product-specific sensitization in wheat tolerant rats. Sensitization to acid hydrolyzed gluten products is associated with a more diverse IgE reactivity profile to unmodified gluten proteins compared to sensitization induced by unmodified gluten or enzyme hydrolyzed gluten. Conclusion: Acid hydrolysis enhances the skin sensitizing capacity of gluten and drives IgE reactivity to more gluten proteins. This property of acid hydrolyzed gluten may be related to the degree of product deamidation, and could be a strong trigger of wheat allergy in susceptible individuals.

The role of skin inflammation, barrier dysfunction, and oral tolerance in skin sensitization to gluten‐derived hydrolysates in a rat model

“…This phenomenon warrants further investigation, including the study of other allergens, the amount of allergen required to sensitize via the skin, the kinetics of IgE levels following oral exposure, and the underlying mechanisms. Of note, we have previously observed at clear dose–response in sensitization to gluten‐derived products (5–500 μg), and our results indicated that a 100‐fold reduction in the dose (5 μg) of E Glu could lead to sensitization when applied to the skin 15 …”

“…Skin‐mediated sensitization to the gluten‐derived hydrolysates induced limited IgE cross‐reactivity to Un Glu in wheat‐naïve rats before oral exposure to Un Glu. This is surprising, because we previously found, that all the hydrolyzed products retained the native antigenic epitopes present in Un Glu 15 . Indeed, Un Glu‐specific IgG1 levels were comparable to the product‐specific IgG1 levels, indicating that the immune system is exposed to Un Glu epitopes.…”

“…Nevertheless, we found that the acid hydrolyzed gluten products exhibited the greatest sensitizing capacity compared with Un Glu and E Glu, which is in line with previous studies of skin-mediated and intraperitoneal sensitization. 9,15,19,24,[28][29][30] Thus, skin sensitization in BN rats may be a potential tool for evaluating the sensitizing potential of food proteins in food allergy risk assessment. Skin-mediated sensitization to the gluten-derived hydrolysates induced limited IgE cross-reactivity to Un Glu in wheat-naïve rats…”

“…Gluten‐derived product‐specific IgG1 was analysed by indirect ELISA as previously described 9,15 . Briefly, ELISA plates were coated with the respective gluten‐derived product (Un Glu, E Glu, Ac Glu 1, 2, 3).…”

“…We have previously characterized five different gluten‐derived products in order to identify physicochemical properties that affect sensitization via the skin in a Brown Norway (BN) rat model 15 . We found that acid hydrolysis of gluten potentiates product sensitization via the skin, suggesting that acid hydrolyzed proteins in personal care products are potent drivers of inducing allergy through the skin.…”