From the Guidelines

Proteins in wheat are the primary cause of wheat intolerance, specifically coeliac disease.

The proteins responsible for wheat intolerance are gluten, a storage protein found in wheat, rye, and barley, and gliadin, the alcohol-soluble part of gluten with immunodominant properties 1.
These proteins trigger an autoimmune reaction in individuals with genetic susceptibility, leading to villous atrophy, intra-epithelial lymphocytosis, and crypt hyperplasia of the small bowel 1.
The ingestion of gluten results in intestinal damage of varying severity in patients affected by coeliac disease, and the only treatment is a lifetime adherence to a gluten-free diet 1.
Gliadin peptides are presented to T cells, leading to the formation of anti-type 2 transglutaminase antibodies (TG2Ab), pro-inflammatory cytokines, lymphocyte infiltration, and subsequent tissue injury 1.
The presence of TG2Ab in the serum and duodenal histological alterations usually make the diagnosis of coeliac disease straightforward 1.
Serological tests, such as total immunoglobulin A (IgA) and IgA anti-tissue transglutaminase (tTG), are used to diagnose coeliac disease, and intestinal biopsy is used to confirm the diagnosis 1.
A gluten-free diet is the only accepted treatment for coeliac disease, and it requires the elimination of storage proteins found in wheat, rye, and barley 1.

From the Research

Proteins in wheat, such as amylase/trypsin-inhibitors (ATIs), gluten, and lectins, can contribute to adverse reactions in humans, including celiac disease, wheat allergy, and non-celiac wheat sensitivity 2, 3, 4, 5, 6
ATIs, which comprise about 2-4% of the total wheat grain proteins, have been shown to trigger the innate immune system and may play a role in non-coeliac wheat sensitivity 2
Gluten proteins, particularly the gliadin fraction, are the main factor triggering celiac disease, a common enteropathy induced by ingestion of wheat gluten proteins and related prolamins from oat, rye, and barley in genetically susceptible individuals 4, 6
The omega(5)-gliadins, part of the gluten protein fraction, are the major group of proteins responsible for wheat-dependent exercise-induced anaphylaxis (WDEIA) 4
Processing of wheat and related cereals may lead to decreased allergenicity, while genetic engineering technology offers opportunities to eliminate allergens by suppressing gene expression 4, 5

Wheat-related intolerances, including celiac disease, wheat allergy, and non-celiac wheat sensitivity, are complex conditions that involve multiple factors, including genetic predisposition, environmental triggers, and immune system responses 3, 5, 6
The identification of gluten fractions and derived peptides involved in wheat allergy and intolerance, including celiac disease, is crucial for understanding the mechanisms of toxicity and developing effective treatments 6
Recent developments in proteomics have provided an important contribution to the understanding of several basic aspects of wheat protein-related diseases, including the identification of gluten proteins and derived peptides, and the development of sensitive and specific methods for detecting trace amounts of gluten proteins in gluten-free foods 6