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

Abstract

The prevalence of wheat allergy has reached significant levels in many countries. Therefore, wheat is a major global food safety and public health issue. Animal models serve as critical tools to advance the understanding of the mechanisms of wheat allergenicity to develop preventive and control methods. A comprehensive review on the molecular mechanisms of wheat allergenicity using animal models is unavailable at present. There were two major objectives of this study: To identify the lessons that animal models have taught us regarding the molecular mechanisms of wheat allergenicity and to identify the strengths, challenges, and future prospects of animal models in basic and applied wheat allergy research. Using the PubMed and Google Scholar databases, we retrieved and critically analyzed the relevant articles and excluded celiac disease and non-celiac gluten sensitivity. Our analysis shows that animal models can provide insight into the IgE epitope structure of wheat allergens, effects of detergents and other chemicals on wheat allergenicity, and the role of genetics, microbiome, and food processing in wheat allergy. Although animal models have inherent limitations, they are critical to advance knowledge on the molecular mechanisms of wheat allergenicity. They can also serve as highly useful pre-clinical testing tools to develop safer genetically modified wheat, hypoallergenic wheat products, novel pharmaceuticals, and vaccines.

New Perspectives in Food Allergy

“…This latter phenotype is more frequent in patients who work in the food industry (occupational allergies) and is characterized by prevalent respiratory symptoms (asthma and rhinitis), anaphylaxis, and urticaria. The most common causal foods include wheat and other cereals, shellfish, and vegetables [57,58].…”

Pathogenesis of Celiac Disease and Other Gluten Related Disorders in Wheat and Strategies for Mitigating Them

“…Wheat allergy is characterized by IgE and non-IgE mediated immune response resulting in allergic reaction in certain individuals upon the uptake, contact, or inhalation of foods containing wheat (243,244). IgE mediated allergic responses occur immediately after food consumption, are food-specific and reproducible (245) and result from the release of histamine, platelets activator factor, and leukotrienes from mast cells and basophils (246,247).…”

The Global Rise and the Complexity of Sesame Allergy: Prime Time to Regulate Sesame in the United States of America?

“…It is simply assumed to be similar to other food allergies. Most food allergies manifest in two general forms based on the time of appearance of clinical symptoms after exposure and the underlying immune mechanisms involved in eliciting them [3,4,82]. They are: (i) immediate (or Type I or IgE antibody-mediated) hypersensitivity reactions, where symptoms appear within minutes to 3 h; and (ii) delayed (or Type IV or cell mediated) hypersensitivity reactions, where symptoms of reaction appear after 48-72 h of exposure to the food allergens [83,84].…”

“…Mechanisms underlying these two distinct types of reactions are completely different. However, both involve two essential steps: (i) sensitization phase; and (ii) disease elicitation phase [3,4,82]. Although specific mechanisms of these phases for sesame allergy have not been widely studied, they are thought to be similar to other allergies.…”

“…Mechanisms through which sesame seed proteins specifically trigger sensitization in humans are largely unknown. However, based on mechanisms in a mouse model of sesame allergy, and based on the general mechanisms of other food allergies, the following model is proposed (Figure 2) Exposure of a genetically susceptible subject to sesame protein allergens via the oral and/or skin routes results in capture of the allergenic proteins by the professional antigen presenting cells (APCs) (e.g., Langerhans cells in the skin, dendritic cells, macrophages/monocytes in the gut) [3,4,82] ( Figure 2). These APCs process the allergen and present its fragments as peptides in association with the Major Histocompatibility Complex (MHC) class-II molecule to allergen specific naïve T helper (Th) lymphocytes.…”