Gluten and Gluten-Related Disorders, Animation

(USMLE topics) What is gluten? Structure of glutens. Pathology of Celiac (Coeliac) disease, wheat allergy. Also includes non-celiac gluten sensitivity.

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Gluten is not a single protein, but a complex mixture of related proteins that constitute the bulk of protein stores in many grains. These proteins belong to 2 main classes: prolamins and glutelins.
Gluten has unique viscosity properties that give the dough its elasticity. Because of its low costs, wheat gluten is widely used as a thickening or binding agent, and to fortify low-protein food products. For this reason, apart from obvious sources, gluten can also be found in a variety of processed foods, including meat and meat substitutes, as well as medications and nutrition supplements.
Prolamins are of most clinical significance when it comes to gluten-related disorders. In wheat they are called gliadin. Proteins similar to gliadin exist in rye, barley, oat, and their derivatives. These proteins are highly polymorphic, meaning there exist many variations of the same protein. Thus, not only different grains, but also different varieties or even different genotypes of the same grain can produce different gluten compounds. Composition of a particular gluten also varies depending on growing conditions and processing technologies.
Prolamins are the main causative agent of celiac disease. Prolamins are rich in the amino acids proline and glutamine, and are therefore highly resistant to digestion by enzymes of the gastrointestinal tract. Partial digestion of prolamins produces a family of small peptides, that can trigger inappropriate immune response in people with celiac disease. These peptides are known as epitopes. A given patient may react only to a few of these peptides. Different patients may react to different peptides. The most toxic epitope, responsible for strongest reactions in most patients, is a 33-amino acids peptide from wheat alpha-2-gliadin.
While it also contains gluten, oat is safe for most people with celiac disease. This is because the prolamin content in oat is significantly lower than that in the other 3 grains, and the number of people reacting to oat epitopes is relatively smaller.
People with celiac disease usually inherit a genetic predisposition to the disease. They have certain receptors that bind strongly to the epitopes and alert the immune system, specifically T-helper cells, to their presence. Activated T-helper cells release inflammatory cytokines, and attract cytotoxic T-cells to the small intestine. This results in inflammation of the mucosa, villous atrophy, and increased gut permeability. Common gastrointestinal symptoms include bloating and abnormal bowel habits.
Wheat gluten is also involved in wheat allergy. Allergy is an immediate abnormal immune response, usually within minutes of ingestion. The mechanism is similar to other food allergies and involves IgE-mediated release of histamine and other inflammatory chemicals from mast cells. Symptoms include itching, swelling, rash, vomiting, diarrhea, and in some cases, life‐threatening anaphylaxis. Gluten, however, is not always the culprit in wheat allergy. Some people react not to gluten, but to other wheat proteins and pollen proteins.
The most common gluten-related disorder is the so-called non-celiac gluten sensitivity. This term includes all reactions to gluten-containing grains that are not celiac disease or wheat allergy. Pathology is not yet understood, and the terminology maybe a misnomer, because other proteins and carbohydrates present in the grains may also be responsible for the symptoms.