Gastroenterology

Gastroenterology

Volume 129, Issue 3, September 2005, Pages 797-806
Gastroenterology

Clinical–alimentary tract
Natural Variation in Toxicity of Wheat: Potential for Selection of Nontoxic Varieties for Celiac Disease Patients

https://doi.org/10.1053/j.gastro.2005.06.017Get rights and content

Background & Aims: Celiac disease (CD) is an intestinal disorder caused by T-cell responses to peptides derived from the gluten proteins present in wheat. Such peptides have been found both in the gliadin and glutenin proteins in gluten. The only cure for CD is a lifelong gluten-free diet. It is unknown, however, if all wheat varieties are equally harmful for patients. We investigated whether wheat varieties exist with a natural low number of T-cell–stimulatory epitopes. Methods: Gluten proteins present in public databases were analyzed for the presence of T-cell–stimulatory sequences. In addition, wheat accessions from diploid (AA, SS/BB, and DD genomes), tetraploid (AABB), and hexaploid (AABBDD) Triticum species were tested for the presence of T-cell–stimulatory epitopes in gliadins and glutenins by both T-cell and monoclonal antibody–based assays. Results: The database analysis readily identified gluten proteins that lack 1 or more of the known T-cell–stimulatory sequences. Moreover, both the T-cell– and antibody-based assays showed that a large variation exists in the amount of T-cell–stimulatory peptides present in the wheat accessions. Conclusions: Sufficient genetic variation is present to endeavor the selection of wheat accessions that contain low amounts of T-cell–stimulatory sequences. Such materials may be used to select and breed wheat varieties suitable for consumption by CD patients, contributing to a well-balanced diet and an increase in their quality of life. Such varieties also may be useful for disease prevention in individuals at risk.

Section snippets

Database Searches

A wheat gliadin and glutenin subset was extracted from the Uniprot database using the SRS program (www.ebi.ac.uk). All epitope sequences listed in Table 1 were searched for full similarity against this subset using the stand-alone Macintosh (Apple, Cupertino, CA) version of the program PeptideSearch (http://www.mann.embl-heidelberg.de/GroupPages/PageLink/peptidesearchpage.html).

Description of the Different Wheat Accessions

The wheat accessions used in this study were obtained from the small-grain cereal collection maintained by the Centre

Matching of Gliadin- and Glutenin-Derived T-Cell Epitopes With Gluten Proteins

It is unknown if all gluten genes are equally toxic for CD patients. The sequences of hundreds of gluten proteins are available through databases. We have aligned the sequence of 11 T-cell–stimulatory sequences from α-gliadin, γ-gliadin, LMW-glutenin, and HMW-glutenin with the gliadin and glutenin proteins present in the Uniprot database (Table 1). Strikingly, although all γ-gliadins contained 1 or more T-cell–stimulatory sequences, the large majority of the LMW-glutenin and one third of the

Discussion

CD is the most common food intolerance in the Western hemisphere: approximately .5% to 1% of the population is now known to have the disease, although the symptoms vary widely among patients. Classic symptoms include diarrhea, stomachache, and failure to thrive. These are the result of a lesion in the small intestine characterized by villous atrophy. T cells isolated from small intestinal biopsy specimens of patients have been shown to respond specifically to gluten-derived peptides bound to

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    Supported by the Celiac Disease Consortium, an Innovative Cluster approved by the Netherlands Genomics Initiative and partially funded by the Dutch Government (BSIK03009), the Stimuleringsfonds Voedingsonderzoek Leiden University Medical Center, by grants from the European Community (QLRT-2000-00657 and QLRT-2002-02077), and by the Center for Medical Systems Biology, a center of excellence approved by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research.

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