Researchers have identified three fragments in gluten that appear to trigger the autoimmune response in people with celiac disease.
The findings, published online July 21st in Science Translational Medicine, may lead to a more targeted cure for the disease instead of what patients do now—abstain completely from food containing wheat, barley and rye and their by-products.
"If you can (narrow down) the toxicity of an allergen to a few components, that enables you to make a highly targeted therapy in a way that you no longer need to target the whole immune system," said researcher Dr. Robert Anderson of The Walter and Eliza Hall Institute of Medical Research in Victoria, Australia.
In the case of celiac disease, which is not an allergy but an autoimmune disorder, autoantibodies produced in response to gluten damage the lining of the small intestine.
In order to identify the antigenic peptides recognized by the T cells that cause this disease, the researchers asked 244 patients in Australia and Britain to eat gluten-containing cereals over three days. The researchers then analyzed blood samples from the patients to quantify their responses to all celiac toxic prolamins (a class of plant storage protein).
The peptides that stimulated the T cells "were the same among patients who ate the same cereal, but were different after wheat, barley and rye ingestion," the authors report. To their surprise, a sequence from wheat and barley "was immunodominant regardless of the grain consumed."
"Furthermore," they said, "T cells specific for just three peptides accounted for the majority of gluten-specific T cells, and their recognition of gluten peptides was highly redundant."
The surprising finding that "the majority of the immune response to gluten can fall back to just three components of gluten... means the immune response is highly focused on maybe some particular forbidden fragments of the gluten," Dr. Anderson said by telephone.
He and some colleagues have since gone on to design an experimental injectable vaccine containing very small doses of each of the three components.
Sci Transl Med 2010.
Reuters Health Information © 2010