Skin sensitization to modified gluten increases severity of wheat food allergy

The skin plays a crucial role as a protective barrier between the host and the external environment. In recent years, it has been suggested that the skin is a preferential exposure route implicated in the occurrence of food allergies. In this study, products derived from gluten produced by enzymatic hydrolysis (E Glu) or by acid hydrolysis (Ac Glu, 1-3) as well as a native gluten (UnGlu) were compared for their capacity to sensitize by the skin of rats and then to induce food allergy to native gluten by the oral route.

Rats sensitized through the skin to different gluten-derived products show different allergic reactions.

Analysis of the properties of different glutens

The enzymatically hydrolyzed product was found to contain small peptides with a peptide size distribution profile distinct from other acid hydrolyzed gluten extracts. The acid-hydrolyzed extracts all contained numerous peptides (amino acid sequence) of widely varying sizes and often chemically modified. The acid hydrolysis of gluten thus generated new epitopes while retaining the epitopes initially present in the native gluten.

The sensitizing power of gluten products

Native gluten and all other gluten extracts were able to induce sensitization in a dose-dependent manner through the skin in rats. Following the oral triggering of the food allergy reaction, swelling of the ear was observed, characteristic symptoms of the allergic reaction. Allergy markers such as gluten-specific IgE and IgG1 were measured. The study showed that acid-hydrolyzed gluten extracts induced higher IgE levels than unmodified or enzymatically hydrolyzed gluten. All extracts were found to induce similar levels of IgG1. The IgE thus produced were also able to bind to native gluten thus suggesting a cross-reactivity between modified and native gluten reinforcing their relevance in gluten allergy and the possibility of sensitization to native gluten by using cosmetic products containing gluten extracts. amended.

In order to examine the ability of gluten extracts to sensitize gluten-tolerant individuals, rats were previously made tolerant to wheat and then the ability of gluten extracts to break this tolerance and induce sensitization was measured. Only acid hydrolyzed gluten extracts were able to sensitize tolerant rats. These acid-hydrolyzed extracts are similar to those identified in cosmetic products responsible for more than 2,000 cases of wheat allergy in Japan where several patients experienced allergic symptoms following ingesting food products containing unmodified wheat. This observation can be explained by the fact that sensitization by the skin to modified wheat gluten can induce IgE capable of reacting to unmodified gluten and consequently cause an allergic reaction following ingestion of native gluten even in individuals previously gluten tolerant. Indeed, acid-hydrolyzed gluten extracts contain both modified epitopes and native epitopes for which tolerance may be low or incomplete.

In conclusion, this study is a step forward in understanding the phenomena of sensitization by the skin and the induction of food allergy to wheat. In particular, products derived from the acid hydrolysis of gluten showed an increased sensitization capacity, and a diversification of activated IgE antibodies. Furthermore, these acid hydrolysis products of gluten are also capable of inducing sensitization in wheat-tolerant subjects.

SCIENTIFIC PARTNERS : A.-SR Ballegaard, JM Larsen, CB Madsen, KL Bøgh, National Food Institute, Technical University of Denmark

FUNDING: COST FA1402 Improving Allergy Risk Assessment Strategy for new food proteins (Imparas)

PUBLICATIONS ASSOCIEES : Mol Nutr Food Res. 2021 Dec; 65 (23): e2100416. doi: 10.1002 / mnfr.202100416. Acid Hydrolysis of Gluten Enhances the Skin Sensitizing Potential and Drives Diversification of IgE Reactivity to Unmodified Gluten Proteins. Anne-Sofie Ravn Ballegaard, Laure Castan, Jeppe Madura Larsen, Cristian Piras, Clélia Villemin, Daniel Andersen, Charlotte Bernhard Madsen, Paola Roncada, Susanne Brix, Sandra Denery-Papini, Gabriel Mazzucchelli, Grégory Bouchaud, Katrine Lindholm Bøgh
https://doi.org/10.1002/mnfr.202100416

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