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Toxic chain. Gluten is digested (1-3) into a "33-mer" that enters the intestine (4) and triggers a reaction from immune cells (5-6).

Gluten Allergy Puzzle Solved

A relatively common disorder of the digestive system called celiac disease prevents people from eating most grain products. Now researchers have discovered the peptide responsible for celiac sufferers' reactions, and they suggest a way to treat the disease. Currently its only treatment is an extremely restricted diet.

Celiac disease affects about 1 in 200 people. When they consume anything containing gluten--a type of protein found in wheat, barley, and rye--their immune systems attack it, prompting severe intestinal inflammation. Recently, scientists found that a common enzyme called tissue transglutaminase, or tTGase, chemically modifies gluten. Mysteriously, in people with gluten intolerance, this modification activates the immune system's T cells and leads to inflammation.

After his wife and son were diagnosed with celiac disease (it has a genetic component), Stanford University chemist Chaitan Khosla decided to hunt down the disease's cause himself. His research team exposed a common gluten protein to digestive enzymes from the human stomach and pancreas. The researchers identified a chain of 33 amino acids in the gluten that wasn't digested. To see if this peptide is responsible for the immune reaction seen in celiac disease, Khosla's group combined it with tTGase. They found that the chain was a prime target of the enzyme. Furthermore, T cells from patients with celiac disease proliferated when exposed to the peptide, suggesting that it was responsible for the uncontrolled immune response, the group reports in the 27 September issue of Science.

Based on their find, the researchers propose two treatments. One would be supplements of an enzyme, found in certain bacteria, that they found degrades the hardy chain. Alternatively, a vaccine based on the peptide might desensitize patients' immune systems.

The find "adds significantly to the already existing body of evidence," says immunologist Frits Koning of the University of Leiden in the Netherlands. But because the newly uncovered amino acid chain is not unique to celiac patients, "it is not the peptide itself that does the trick. There are probably other genetic and environmental factors involved."

Related sites
Abstract of Science paper
Chaitan Khosla's home page
Celiac Disease Foundation