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

乳糜泻影响了大约1%的高加索人和西亚人，大约25万澳大利亚人。乳糜泻的诊断是有问题的，不到五分之一的患有乳糜泻的澳大利亚人被诊断出来，而更多的人采用无麸质饮食，严格避免小麦、大麦、黑麦和燕麦制成的食物，错误地认为自己患有乳糜泻。如果公众要从对乳糜泻的新认识中获益，就迫切需要易于实施和为患者所接受的新诊断和治疗方法。这是一个不幸的错误，免疫系统识别和反应谷蛋白与乳糜泻的人。感知谷蛋白并破坏肠道的免疫细胞，t细胞，只能检测到谷蛋白的非常特定的短片段（表位）。了解哪些麸质片段会导致乳糜泻，将有助于新的测试来诊断乳糜泻，设计无毒的麸质，甚至可能带来新的治疗方法，可以使免疫系统对麸质脱敏，就像脱敏治疗对过敏一样。对引起乳糜泻的麸质碎片的了解正在改善，但仍不完整。我们开发了一种简单的测试方法可以精确定位任何乳糜泻患者都能识别的谷蛋白片段。在患有乳糜泻的志愿者和面筋蛋白碎片库的帮助下，我们将能够绘制出小麦、大麦、黑麦和燕麦中刺激t细胞的面筋的所有区域。我们将找到最有效的表位，可用于诊断测试，食品测试和脱敏治疗。研究患有乳糜泻的人在食用燕麦（通常是乳糜泻患者禁止食用的食物，但对燕麦的实际反应少于1:4）时的情况，将确定对这种谷物产生破坏性或耐受性反应后肠道组织的变化，并提供评估未来乳糜泻脱敏疗法的工具。

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.