Linking To And Excerpting From Food Chemistry: X “Allergens from wheat and wheat products: A comprehensive review on allergy mechanisms and modifications”

Posted on June 18, 2026 by Tom Wade MD

Today, I review, link to, and exccerpt from Food Chemistry: X, Allergens from wheat and wheat products: A comprehensive review on allergy mechanisms and modifications. [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Food Chem X. 2025 Aug 5:29:102871. doi: 10.1016/j.fochx.2025.102871. eCollection 2025 Ju

All that follows is from the above article.

Abstract

Wheat is one of major human staple foods, contributing an important source of dietary protein. However, some people are allergic to wheat-based foods. They are accompanied by many symptoms, such as wheat dependent exercise induced anaphylaxis, atopic dermatitis, anaphylactic shock, which seriously affect the quality of life. Food processing technologies were proven affecting allergen allergenicity to varying degrees. Therefore, it is imperative to use effective methods to reduce wheat sensitization. This manuscript summarizes the mechanisms of wheat allergy, antigenic epitopes, cross-allergy with other cereals, and animal model studies. Then, the various modifications used to reduce wheat sensitization and their advantages and disadvantages are described. Among them, high hydrostatic pressure treatment has become a research hotspot because of its non-thermal in nature, giving better retention of nutritional value and sensory properties of the final product, and significantly reducing the allergenicity.

Keywords: Wheat, Allergens, Mechanism, Modification

Highlights

  • Wheat allergy has caused significant dietary problems in allergic populations.
  • Wheat allergens.
  • High hydrostatic pressure technology can reduce allergenicity while retaining nutritional value and sensory properties.
  • Bioinformatics prediction of epitopes can effectively assess potential sensitization of unknown allergens.
  • Animal testing is an effective method for validating the results of desensitization research before application.

1. Introduction

Wheat (Triticum aestivum L.) is a cereal plant widely grown around the world with its global importance as one of the staple grains, which cannot be overstated. The production of wheat in 2024 was 792.2 million tons, which was about 27.8 % of the global cereal production (). About 40 % of the global population depends on these sources for almost all of their daily energy needs. Wheat is nutritious and rich in starch, protein, lipids, minerals, vitamins, etc., and its nutritional value ranks among the top of the cereals, providing about 20 % of daily dietary calories and proteins, and the comparison of the nutritional composition of other cereals is shown in Table 1(). However, wheat contains allergenic proteins which cause allergic reactions (), and pose serious health hazards to some individuals.

In 2023, the U.S. Food and Drug Administration (FDA) officially listed sesame as the ninth major food allergen. After that, milk, soybeans, wheat, tree nuts, peanuts, shellfish, fish, eggs, and sesame have become the main causes of most food-related allergic reactions () (Fig. 1). Of which milk and egg allergens are the most prominent (), and wheat has become one of the most common food allergens after egg and milk in China (). The incidence of wheat allergy has been steadily increasing worldwide, and more and more people have paid attention to it. Wheat allergies can lead to a range of disorders including wheat dependent exercise induced anaphylaxis, baker’s asthma, atopic dermatitis, anaphylactic shock, etc. These symptoms usually appear within minutes to hours of exposure, and the sudden whole-body reaction leads to drop in blood pressure, which in severe cases can be fatal to patient by anaphylactic shock().

Fig. 1

Fig. 1

Big 9 allergens.

Additionally, the prevalence of wheat allergy varies from region to region and from population to population (). Infants are particularly susceptible to allergic reactions when exposed to food allergens, primarily due to inadequate production or secretion of digestive enzymes. However, as they mature, the development of their gastrointestinal system may alleviate these symptoms (). One study found that the median age of tolerance in these patients was 7 years (3–16 years), and allergy tolerance by the ages of 8, 12, and 16 years was 52 %, 66 %, and 76 %, respectively (). In a meta-analysis of the global prevalence of wheat allergy, the global self-reported prevalence of wheat allergy was 0.63 %, with 0.58 % in children (). Based on epidemiologic studies, the self-reported lifetime prevalence of wheat allergy in Europe was as high as 3.6 % (), and researchers showed that about 0.2 %–0.5 % of children under 14 in Europe were allergic to wheat ().  found that the prevalence of wheat allergy in Japanese adults was 0.21 %, which was conducted by using a questionnaire, skin prick test and the serum omega-5 gliadin-specific IgE test. In another study, the Japan Environment and Children’s Study (JECS) of 103,060 pregnant women and their children found that the prevalence of immediate wheat allergy reported by caregivers was 0.5 %, 0.4 %, and 0.2 % at age 1, 2, 3 years, respectively ().  investigated the self-reported prevalence of food allergy in six districts in Inner Mongolia, northern China, which showed that the prevalence of food allergy was high in this region (18.0 %), with as many as 3.6 % of children showing allergic to wheat. There are many factors that contribute to these differences, including genetic background, dietary habits, and environmental factors.

Currently, an effective treatment strategy for wheat allergy patients is strict avoidance of wheat allergens (). With the rapid development of food industries, the incidence of food allergy is increasing year by year globally with more and more cross-contact between various food ingredients, which makes it difficult to strictly avoid the contact with allergens. Oral immunotherapy (OIT) has received research attention as an alternative to desensitization due to its ability to modify abnormal immunologic mechanism of IgE-mediated food allergy. While permanent tolerance is not often achieved, desensitization can be achieved and maintained with daily ingestion of the offending food (). However, few clinical trials have been conducted on wheat OIT, and there is safety concerns associated with OIT, with the possibility of adverse reactions in food-allergic patients during the dose escalation phase. Therefore, it is particularly important to develop hypo/non-allergenic products by modifying wheat and wheat products using different food processing methods. Nowadays, a variety of food processing technologies have been successfully applied to reduce the allergenicity of wheat products, and a range of products have emerged, such as hypoallergenic breads, noodles, cookies, pasta and sauces. The degradation of allergens in these products is mainly achieved through heat treatment, enzymatic treatment, fermentation processes or deamidation (). However, there are still important challenges to develop more diverse and safer hypoallergenic wheat food products using more efficient technologies in order to meet the growing dietary needs of wheat-allergic populations.

In this review, we provide an overview of the mechanism of wheat allergic reactions, major allergens, antigenic epitopes, and cross-allergy with other cereals. The processing methods to eliminate or reduce wheat allergens are discussed, while animal experimental models are introduced that can objectively simulate the allergic reactions induced by the food in vivo. This review aims to provide basic information to researchers, common man and allied stakeholders (), not only to provide a certain reference value for further research on wheat processing and utilization, but also to maximize the benefits of wheat as a protein source and minimizing the adverse effects of wheat allergy.

2. Wheat allergy

2.1. Mechanisms of wheat allergy

The pathogenesis of wheat allergy is similar to that of other common food allergies, where the allergen is transported to immune cells, ultimately causing allergic symptoms (). Current research suggests the following three mechanisms of reaction to food allergy: IgE-mediated food allergy, non-IgE-mediated food allergy, and food allergy mediated by a combination of the two (). Wheat allergy is primarily a type I allergic reaction mediated by IgE (), including three stages of sensitization, excitation and effect (). When food allergens or allergenic fragments enter the body of allergic patients for the first time, they pass through the gastrointestinal mucosa, which are captured by antigen presenting cells and presented to T cell receptors, leading to T cell activation and differentiation into Th2 cells. The Th2 cells secrete cytokines, such as interleukin-4 (IL-4), which can induce B lymphocytes to transform into plasma cells. Plasma cells then release specific IgE antibodies, which spread throughout the body as the blood circulates, bind to mast cells and high-affinity receptors on the cell membrane of basophilic granulosa, making these cells become target cells for sensitization, making the body in the sensitization stage (). When the sensitized organism is re-exposed to the allergen, it specifically binds to the IgE antibodies already bound to the target cells, inducing the cells to undergo a degranulation reaction, releasing histamine, leukotrienes, and other reactive mediators. These active mediators can cause an inflammatory response, acting on the effector tissues and organs, thereby triggering a local or systemic allergic reaction ().(Fig. 2).

Fig. 2

Fig. 2

Immunoglobin E (IgE)-mediated food allergy mechanism.

Clinical symptoms usually manifest as respiratory problems, such as conjunctivitis, rhinitis, and asthma, while skin reactions, such as hives, eczema, and itching (). Moreover, it also causes gastrointestinal problems, such as vomiting, abdominal pain, and diarrhea as well as symptoms, such as low blood pressure and impaired thinking (). These symptoms usually appear within minutes to hours of exposure.

2.2. Types of wheat allergens

Wheat allergy is caused by a wide variety of allergens. Different wheat allergens have different pathogenic mechanisms, and allergic patients experience different clinical symptoms (). Both the establishment of wheat allergen detection methods and the search for methods to reduce allergenicity need to be based on the premise of clarifying information about the major wheat allergen proteins. Based on the solubility of the proteins, wheat proteins are usually classified into three categories, namely gliadin, glutenin, and soluble proteins. Of these, gliadin accounts for about 40–50 %, glutenin for about 30–40 % and soluble proteins for about 15–20 % (; ). As of September 21, 2023, WHO/IUIS Allergen Nomenclature Sub-Committee have approved 28 wheat allergens, which can be categorized into 9 foodborne allergens and 19 inhalant allergens, depending on exposure conditions. Food allergy to wheat is more common in children and is a concern because of the high risk of exposure with severe allergic reactions, and inhaled wheat allergy can trigger asthma or rhinitis in bakers, which is a common occupational disease among workers with high exposure to wheat flour, such as bakers (). The biochemical names, molecular weights, and allergen exposure routes of these foodborne allergens are listed in Table 2.

2.2.1. Gliadin

Gliadin exists as peptide single chains, rich in glutamine and proline, which can be classified into four isoforms, namely α, β, γ and ω; Such classification is based on their electrophoretic mobility, with sensitization present in each isoform(). They are highly fluid and help to enhance the stickiness and extensibility of the dough. Both α- and β-gliadin proteins have comparable primary structures consisting of around 250 and 300 AA residues; α-gliadin are more damaging to the mucous membranes of the intestines, showing a major allergen in wheat allergy and celiac disease ().  showed that γ-gliadin is a major allergen that triggers wheat-dependent exercise-induced anaphylaxis, which also showed to be an important allergen in celiac disease. In addition,  showed that ω5-gliadin is also a major allergen that triggers wheat-dependent exercise-induced anaphylaxis.

2.2.2. Glutenin

Glutenin molecules are connected by disulfide bonds; their amino acids are mostly polar amino acids, which easily aggregate, giving the dough strength and elasticity (). According to the size of relative molecular mass, they can be categorized into high-molecular-weight glutenin subunit (HMW-GS) and low-molecular-weight glutenin subunit (LMW-GS) (). The latter one is an important allergen in susceptible populations, which has been associated with celiac disease and wheat contact dermatitis (). The HMW-GS and ω-5-gliadin are major allergens in wheat-dependent exercise-induced anaphylaxis (WDEIA) and their IgE-binding levels can be an important indicator for assessing WDEIA ().

 

 

Posted in Food Allergies, Food Chemistry: X, Wheat Allergy | Comments Off on Linking To And Excerpting From Food Chemistry: X “Allergens from wheat and wheat products: A comprehensive review on allergy mechanisms and modifications”