CONTAINMENT OF THE T-CELL RESPONSE TO GLUTEN IN COELIAC DISEASE

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Coeliac disease affects about 1% of Casucasians and West Asians, about 250,000 Australians. Diagnosis of coeliac disease is problematic, less than one fifth of Australians with coeliac disease have been diagnosed, while many more adopt a gluten free diet and strictly avoid foods made from wheat, barley, rye and oats mistakenly thinking that they have coeliac disease. New diagnostics and therapies that are easy to perform and acceptable to patients are badly needed if the public are to benefit from emerging understanding of coeliac disease. It is an unfortunate mistake that the immune system recognizes and reacts to gluten in people with coeliac disease. The immune cells that sense gluten and damage the intestine, T-cells, detect only very specific short fragments (epitopes) of gluten proteins. Understanding which gluten fragments cause coeliac disease would enable new tests to diagnose coeliac disease, design of non-toxic gluten, and may even allow new treatments that could desensitise the immune system to gluten in the same way that desensitisation therapy works for allergy. Understanding of the gluten fragments causing coeliac disease is improving but it is still incomplete. We have developed a simple test that can pin-point the gluten fragments recognized by any individual with coeliac disease. With the help of volunteers with coeliac disease and a library of fragmented gluten proteins, we will be able to map all the regions of gluten in wheat, barley, rye, and oats that stimulate T-cells. We will find the most potent epitopes that could be used in diagnostic tests, food tests, and desensitisation therapy. Studying individuals with coeliac disease when they eat oats, normally a forbidden food for coeliac suffers yet fewer than 1:4 actually react to oats, will define the changes in intestinal tissue following destructive or tolerant responses to this grain and provide a tool to assess future desensitisation therapies for coeliac disease.