Study: Research Provides New Insight into Gluten Intolerance

19 Nov 2014 --- Celiac disease patients suffer from gluten intolerance and must adjust to a life without gluten from food sources like wheat, rye and barley. There is no treatment of the disease except lifelong gluten-free diet, but now a Danish/Norwegian research team publishes new research, that may lead to the development of a drug against the disease.

Gluten intolerance is often caused by celiac disease, which makes the human organism sensitive to gluten proteins from certain cereals. No known drug can cure the disease or make the patient able to eat gluten again, and therefore the patients have to completely refrain from eating gluten-containing foods.

Now a Danish/Norwegian research team from the University of Southern Denmark and the University of Oslo/Oslo University Hospital has managed to retrieve hitherto unknown details about what is happening in the body of a celiac patient who eats gluten.

"We've got a new fundamental understanding of the pathological mechanisms in celiac disease, and it opens the possibility to develop new drugs against this disease”, says head of research, associate professor and ph.d., Thomas J. D. Jørgensen, Department of Biochemistry and Molecular Biology, University of Southern Denmark.

The research team published their results in the journal PNAS.

The first authors are former ph.d. student Simon Mysling from University of Southern Denmark and postdoc Rasmus Iversen from the University of Oslo. Thomas J. D. Jørgensen and Professor Ludvig M. Sollid from the University of Oslo/Oslo University Hospital led the research.

Doctors know that celiac disease is a so-called autoimmune disease. This means that gluten activates the body's immune system so that it starts to attack the body itself. In particular the immune system attacks the mucosa of the small intestine, so it weakens and loses its capability to absorb nutrients properly.

When the immune system is activated, it produces antibodies that attack a particular enzyme in the body. Exactly how this interaction between antibodies and enzyme plays out has until now been unclear, but now the research team presents new details about how the antibodies are formed and behave as well as how the enzyme reacts to different stimuli.

"We now have an insight into how the antibodies react when they encounter the enzyme. We also know how the enzyme changes shape when exposed to different environmental impacts, such as the concentration of calcium ions changes ", explains Thomas J.D. Jørgensen.

Ref: Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange. Rasmus Iversen, Simon Mysling, Kathrin Hnida, Thomas J. D. Jørgensen and Ludvig M. Sollid. PNAS.