Scientists from Melbourne’s Walter and Eliza Hall Institute have identified the three protein fragments that make gluten, which is toxic to people with celiac disease. Gluten is the main protein in wheat, rye and barley.
A vaccine based on the discovery has entered clinical trials.
A press release from the Walter and Eliza Hall Institute is available here.
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Dr Bob Anderson is head of the Walter and Eliza Hall Institute’s Coeliac disease research laboratory and one of the researchers involved in the study
“This study has identified what is known as the ‘canonical’ toxic sequence that explains why wheat, rye and barley are all toxic to people with coeliac disease.
In the 60 years since gluten was discovered to be the environmental cause of coeliac disease, there has been a search for the disease mechanism and specifically the “toxic gluten peptide/s” that cause coeliac disease.
Although often overlooked or misdiagnosed, coeliac disease is readily diagnosed by a combination of blood tests and biopsy of the small intestine. The only currently available treatment is a diet free of gluten – the main protein in wheat, rye and barley grains. Our discovery opens the way for a new generation of diagnostics, treatments, prevention strategies and food tests for the 200,000 Australians with coeliac disease.
This study has also led to coeliac disease being the first human immune disease for which there is a definitive understanding of the disease-causing immune responses; its findings have implications far beyond coeliac disease. Two-thirds of genes implicated in coeliac disease are shared with other autoimmune and inflammatory disorders. Our findings suggest that other genetically related immune diseases such as type 1 diabetes could be amenable to highly targeted immunotherapy, diagnosis and prevention.”
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Dr Robert Loblay is Director of the Allergy Unit at Royal Prince Alfred Hospital, NSW
“The results of the study are of considerable theoretical interest to immunologists interested in how T cells go about their business of reacting to complex antigens in a real-life setting. Studying this in people with coeliac disease makes it doubly interesting because coeliac disease happens to be the first human autoimmune disease where an environmental (dietary) trigger has been identified. This makes it an excellent experimental model for fundamental studies of the disease process.
Whether or not these findings will translate into a safe, practical and clinically effective vaccine that would allow people with coeliac disease to eat gluten-containing foods remains to be seen. If the current candidate vaccine passes the short term (Phase I) safety tests, and immunological activity is demonstrated in subsequent Phase II studies, the next step will be to determine long-term safety & efficacy in a large-scale Phase III trial. This is likely to take many years, and because of uncertain long-term effects on gastrointestinal cancer risks (known to be increased in people with active coeliac disease) lifelong surveillance of vaccine recipients will be required.
Even if a candidate vaccine eventually proves to be safe & effective in the long-term, it will still have to prove itself to be more convenient and cost-effective than the alternative (dietary gluten avoidance) which is getting easier to manage with every passing year.”