Research Topic

The Molecular Aspects of Gluten-Related Disorders

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About this Research Topic

The term Gluten-Related Disorders (GRD), refers to pathologies caused by the ingestion of wheat-based food. Celiac disease (CD) wheat allergy (WA) and non-celiac gluten sensitivity (NCGS) are different forms of gluten-related disorders. Epidemiologic studies have underlined a worrying increase of GRDs ...

The term Gluten-Related Disorders (GRD), refers to pathologies caused by the ingestion of wheat-based food. Celiac disease (CD) wheat allergy (WA) and non-celiac gluten sensitivity (NCGS) are different forms of gluten-related disorders. Epidemiologic studies have underlined a worrying increase of GRDs worldwide in wheat consuming countries.

CD is the most studied gluten intolerance, where the intake of gluten, contained in wheat and related cereal (barley and rye), triggers an immune reaction predominantly in the small intestinal mucosa, that appears, in the most severe of cases, with intestinal villous atrophy. Gluten proteins are markedly resistant to gastrointestinal digestion, resulting in the release of long peptides that stimulate inflammatory immune responses in subjects genetically predisposed. Both an adaptive, and innate immune, responses are elicited by undigested gluten peptides. To date, several gluten peptides have been identified to stimulate intestinal T cell responses in HLA-DQ2/DQ8 positive CD patients. In concert with the adaptive immunity, some gluten peptides elicit an innate immune response, and both immune pathways contribute to gut mucosa damage.

Wheat allergy represents another type of GRD, where the ingestion of wheat and related cereals might induce IgE-mediated reaction, in both adults and children. Wheat proteins have been found to trigger different IgE-mediated allergic reactions which are classified as: Baker's asthma, food allergy and wheat-dependent exercise-induced anaphylaxis (WDEIA). Research studies indicate that many proteins are involved in wheat allergy, such as alpha-amylase trypsin inhibitor (Baker's asthma), no-specific lipid transfer proteins (food allergy) and omega-5-gliadin (WDEIA).

While CD and wheat allergy have been widely studied, the mechanisms inducing the NCGS are still far from being explained. NCGS is defining as the condition in which consumption of wheat triggers gastrointestinal and extra intestinal symptoms in patients with any celiac-specific antibodies and villous atrophy as well as any allergy related process. Though the occurrence of NCGS is associated with the assumption of gluten, recent evidences suggest that some components of wheat other than gluten may trigger symptoms. Nowadays, because of the absence of reliable biomarkers, NCGS diagnosis is based on the exclusion of CD and wheat allergy, and after the disappearance of symptoms upon a gluten-free dietary regime. Recent evidences suggest the involvement of innate immunity where an alpha-amylase trypsin inhibitor may be the triggering factor.

To date, the only treatment for the GRDs is the strict lifelong gluten-free diet. Efforts are required to unravel the mechanisms behind the GRDs, as well as to develop new and alternative therapies to gluten-free diet. This Research Topic will provide a comprehensive overview on the molecular aspects and on novel frontiers for therapeutic and preventive management of GRD.

We welcome the submission of Reviews, Mini-Reviews and Original Research articles covering, but not limited to, the following themes:

1. The molecular and cellular mechanisms of CD.
2. The molecular and cellular mechanisms of WA.
3. The pathogenesis of NCG.
4. The digestion properties of gluten proteins.
5. how the diversity of wheat landraces has beneficial impact on human health.
6. Novel therapeutic frontiers for GRDs.
7. Prevention of GRDs.


Keywords: Celiac Disease, Wheat Allergy, Non-Celiac Gluten Sensitivity, Innate Immune Response, Adaptive Immune Response, Gluten Protein, Immunogenic and Toxic Peptides


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