Celiac disease, wheat allergy, and nonceliac sensitivity to gluten: topical issues of the pathogenesis and diagnosis of gluten-associated diseases

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Abstract

Historically, wheat and other gluten-containing grains have been an essential part of the diet of many people worldwide. However, the widespread use of gluten-containing products has led to an increased incidence of adverse reactions associated with their consumption, such as celiac disease and wheat allergy, as well as nonceliac gluten sensitivity, which has become common in recent years.

Gluten-associated diseases have similar clinical manifestations (abdominal pain, bloating, diarrhea, nausea, and vomiting). The pathogenetic mechanisms underlying celiac disease and wheat allergy are quite well understood; in both cases, an immune response occurs when wheat proteins are consumed, both with effective treatment. Nonceliac gluten sensitivity is the subject of discussion; however, the processes underlying this disease are not fully understood; thus, its diagnosis and treatment have no unified approach. To date, nonceliac gluten sensitivity is a diagnosis of exclusion, which is established in the absence of markers of celiac disease or wheat allergy and improved following a gluten-free diet.

A gluten-free diet is the most effective treatment for gluten-related diseases. However, like any other strict dietary restriction, gluten avoidance can result in reduced intakes of important nutrients, such as dietary fiber, protein, and micronutrients. In recent years, an increasing trend is found in the general population without confirmed gluten-related disorders that gluten-free product consumption or gluten-free diet adherence since gluten avoidance can improve well-being or gluten can be toxic for all human beings

According to current guidelines, only patients diagnosed with celiac disease or wheat allergy are advised to follow a strict gluten-free diet.

Herein, the modern conception of the immunopathology of gluten-related diseases and an overview of new potential therapies are presented.

About the authors

Yuliya A. Kaminarskaya

Chaika Healht

Author for correspondence.
Email: osipovaulia@gmail.com
ORCID iD: 0000-0002-9893-3292
SPIN-code: 1333-6058

MD

Russian Federation, 49-2, Bolshaya Academicheskaya street, Moscow, 125008

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2. Fig. 1. Pathogenesis of celiac disease. After deamination of gluten peptides process of antigen-presentatiom begins. HLA2-DQ2/DQ8 in antigen presenting cells (APC) present this peptides to CD4+ T-cells which are key in the initiation of the inflammatory response. On one hand, they promote a Th1 response in which large amounts of IFN-γ and IL-21 are produced contributing to the activation of Intestinal intraepithelial lymphocytes (IELS). CD4+ T-cells also induce a Th2 response and promote the clonal expansion of B-cells and production of IgA antibodies against TG2 and gliadin.

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3. Fig. 2. Pathogenesis of wheat allergy. Wheat allergy can be triggered by several wheat proteins, named as allergens. Th2 cells play an essential role in the induction of IgE by B-cells in the initial phase of the allergic response. After a new consumption of allergen, IgE antibodies bound to their receptors on mast cells and basophils, recognize specific, which leads to consequent cell activation and release of inflammatory and vasoactive mediators. As a result, allergic inflammation is elicited.

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4. Fig. 3. Possible mechanism of nonceliac gluten sensitivity. The pathogenesis is expected to be based on innate immune responses due to the activation of TLR receptors of immune cells. In addition to the influence of gluten, amylase and trypsin inhibitors (ATIs), fermentable oligo-, mono-, disaccharides, polyols (FODMAPs) can also activate dendritic cells and macrophages through TLR4 and play a potential role in the development of non-celiac gluten sensitivity. This interaction results in the release of pro-inflammatory cytokines and chemokines, infiltration of tissues by eosinophils, but does not lead to damage to the intestinal mucosa. АПК ― antigen presenting cells.

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