Designing individual treatments for coeliac disease

July 24, 2007

Treatments individually tailored to the 200,000 Australians with coeliac disease are now closer following research by Monash scientists and colleagues into the disease.

Often overlooked or misdiagnosed, coeliac disease is currently treated by removing gluten from the patient’s diet.
Gluten is the main protein in wheat, rye and barley grains. In people with coeliac disease, gluten inflames and damages the lining of the small intestine, hampering its ability to absorb nutrients from food.

The team of Kate Henderson and Professor Jamie Rossjohn from Monash University, Dr Jason Tye-Din and Dr Robert Anderson from Walter and Eliza Hall Institute (WEHI), Professor Jim McCluskey from Melbourne University and colleagues discovered the immune response in people with the DQ8 form of coeliac disease was quite different to that of DQ2. Their findings are published in the current issue of the international journal Immunity.

Dr Anderson said crucial to the research was the discovery that T-cells (white blood cells that play a critical role in the immune response) in people with DQ8-associated coeliac disease reacted quite differently to the small proteins in gluten than the T-cells in people with the DQ2 from of the disease.

“At the molecular level there’s quite a different immune response to the gluten,” Dr Anderson said. “It is sufficiently different to the reaction with DQ2 that different therapies would be appropriate for people with the DQ8 form of coeliac disease.”

People’s susceptibility to coeliac disease is determined by two major genes – DQ2 and DQ8. The first form of gene is common in people in North America, Europe and Australia. About 95 per cent of coeliac patients have DQ2.

In China and East Asia, the DQ2 genes are rare while DQ8 genes are common. Although there is a commonly-held belief that coeliac disease doesn’t occur in East Asia and China it is likely that as Asian diets become more Western and therefore include more wheat – people diagnosed with the disease will increase.

When people with coeliac disease eat or drink products containing gluten, their body’s immune response is switched on and damage is done to the intestine. It had been assumed the molecular workings underpinning this immune response in the DQ2 and DQ8 forms of the disease were similar and that any potential treatments could apply equally to both forms.

At the moment a gluten-free diet is the only treatment for coeliac disease. However nearly half the people on the diet still have damage to their small intestine. Consequently other therapies, including a vaccine and three different drugs, are in various stages of development.