Study Identifies Major Peptide Culprits in Celiac Disease

Discovery could lead to progress in developing disease immunotherapies or prevention strategies

THURSDAY, July 22 (HealthDay News) -- The overactive immune response to gluten that characterizes celiac disease results mostly from a limited number of peptides activating pathogenic T cells, suggesting that the disease might be prevented by developing nontoxic gluten products or be treated with immunotherapy, according to a study in the July 21 issue of Science Translational Medicine.

Jason A. Tye-Din, Ph.D., of the University of Melbourne in Parkville, Australia, and colleagues fed more than 200 patients with celiac disease foods containing wheat, barley, or rye for three days to induce an immune response to gluten. Six days after induction, the researchers took blood samples and screened peripheral blood mononuclear cells using a high throughput enzyme-linked immunosorbent spot assay to identify the peptides that stimulated T cells in the immune response.

Overall, the researchers assessed responses to 2,700 different peptides, with 90 peptides resulting in some level of immune response. However, three peptides were found to be particularly toxic, with T cells responsive to those peptides responsible for most of the immune response, suggesting that it might be practical to develop celiac disease immunotherapies. The researchers also identified a single peptide responsible for the toxicity shared by wheat, barley, and rye.

"Our findings show that pathogenic T cells in celiac disease show limited diversity, and therefore suggest that peptide-based therapeutics for this disease and potentially other strongly human leukocyte antigen-restricted immune diseases should be possible," the authors write.

A number of study authors hold patents pertaining to the use of gluten peptides in therapeutics, diagnostics, and the development of nontoxic gluten; several authors disclosed financial ties to companies developing peptide-based therapeutics, diagnostics, and nontoxic gluten suitable for celiac disease patients.

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