Toxic fragments in gluten that cause coeliac disease finally identified

It is 60 years since gluten was discovered to be the environmental cause of coeliac disease and for all of those 60 years, researchers have been working to identify the toxic peptide components of gluten. And now, at last, a team at the Walter and Eliza Hall Institute’s coeliac disease research laboratory in Melbourne, Australia, under Dr Bob Anderson, has done just that.

Nine years ago, while at Oxford University, Professor Anderson began looking at the immune response activated in people fed wheat, barley or rye; the most recent phase of his work has involved researchers in Australia and the UK as well as more than 200 coeliac disease patients, recruited through the Coeliac Society of Victoria and the Coeliac Clinic at John Radcliffe Hospital, UK, who 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.

By comparing the type of T-cells found in the patients' blood with a "library" of 16,000 gluten fragments, he and colleagues were able to work out which fragments triggered the biggest immune response. To their surprise, the researchers found that the peptide known to be toxic in wheat gluten was not a problem in the patients fed barley and rye. Instead, the researchers found each of the three grains had their own toxic peptide that triggered an immune response. They also found one peptide, dubbed the "universal toxic peptide", was a problem no matter what grain was eaten. Thus three out of four critical peptides for coeliac disease have now been identified.

Professor Anderson says the findings are being used to develop a new class of drugs, called peptide-based immunotherapy, that involve injecting patients with a small amount of the toxic peptides to desensitise their body to them. The first phase of trials of the therapy to assess safety and tolerability were completed in June, and final results are expected in coming months.

Professor Anderson is the CEO, chief scientist, chief medical officer, director and substantial shareholder of Melbourne-based biotech company Nexpep, which is carrying out trials and helped fund the study.

The study is published in the international journal Science Translational Medicine.

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