Walter and Eliza Hall Institute scientists have identified the three protein fragments that make gluten（面筋，麸质） - the main protein in wheat, rye（黑麦） and barley1（大麦） – toxic2 to people with coeliac disease（乳糜泻） . Their discovery opens the way for a new generation of diagnostics, treatments, prevention strategies and food tests for the millions of people worldwide with coeliac disease.
When people with coeliac disease eat products containing gluten their body's immune response is switched on and the lining3 of the small intestine4（小肠） is damaged, hampering5 their ability to absorb nutrients6. The disease is currently treated by permanently7 removing gluten from the patient's diet.
Dr Bob Anderson, head of the Walter and Eliza Hall Institute's coeliac disease research laboratory, said it had been 60 years since gluten was discovered to be the environmental cause of coeliac disease.
"In the years since, the holy grail in coeliac disease research has been to identify the toxic peptide（缩氨酸） components8 of gluten; and that's what we've done," Dr Anderson said.
The research, done in collaboration9 with Dr Jason Tye-Din, Dr James Dromey, Dr Stuart Mannering, Dr Jessica Stewart and Dr Tim Beissbarth from the institute as well as Professor Jamie Rossjohn at Monash University and Professor Jim McCluskey at the University of Melbourne, is published in today's issue of the international journal Science Translational Medicine.
The study was started by Professor Anderson nine years ago and has involved researchers in Australia and the UK as well as more than 200 coeliac disease patients.
The patients, recruited through the Coeliac Society of Victoria and the Coeliac Clinic at John Radcliffe Hospital, UK, ate bread, rye muffins or boiled barley. Six days later, blood samples were taken to measure the strength of the patients' immune responses to 2700 different gluten fragments. The responses identified 90 fragments as causing some level of immune reaction, but three gluten fragments (peptides) were revealed as being particularly toxic.
"These three components account for the majority of the immune response to gluten that is observed in people with coeliac disease," Dr Anderson said.
This knowledge has already been used by Melbourne-based biotech company, Nexpep Pty Ltd, to develop a 'peptide-based' immunotherapy（免疫疗法） that aims to desensitise people with coeliac disease to the toxic effects of gluten. Nexpep's Phase 1 trials of the therapy were completed in June and final results are expected in coming months.
The immunotherapy works by exposing people with coeliac disease to small amounts of the three toxic peptides and is based upon the same principles as desensitisation（退敏感作用） for allergies10.
Dr Anderson said although coeliac disease could be managed with a gluten-free diet, compliance11 with（符合，遵守） the diet is often challenging and nearly half the people on the diet still have residual12（剩余的，残留的） damage to their small intestine. "Consequently, the immunotherapy and three other drugs are under development to help people with coeliac disease."
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