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Gene mutation in Crohn’s disease stops body-bug chat


A gene commonly mutated in Crohn’s disease sufferers is responsible for allowing the body’s immune system to ‘chat’ to microbes in the gut. Researchers at Hammersmith Hospitals NHS Trust and Imperial College London who have uncovered the role of this gene say that it will now be possible to develop better tests for this debilitating disease, and will help researchers to uncover the genetic basis of Crohn’s and similar inflammatory bowel diseases.

Writing in the journal The Lancet tomorrow (21 May), the Hammersmith researchers describe the effect that mutations in the gene, known as NOD2/CARD15, has on the release of immune system molecules in the gut. Normally, the gene produces a protein that is involved in recognising bacteria in the gut. This recognition prevents the initiation of an early immune response, which subsequently leads to the lining of the gut becoming inflamed. In around a quarter of Crohn’s disease sufferers, mutations in the NOD2/CARD15 gene prevent this communication from taking place.

“The NOD2/CARD15 system was the first genetic defect found to be associated with Crohns disease, but until now we haven’t been able to understand exactly why this caused the disease,” comments study leader Dr David van Heel, gastroenterologist at Hammersmith Hospital and Imperial College London. “Our studies suggest that this defect does not allow the immune system to work properly in the very earliest stages of mounting an immune response."

“The body normally senses microbes present in the gut that are essential in maintaining normal gut function, and there is regular cross-talk between the gut lining and the microbes that they contain. This functional defect probably disrupts this natural process.”

“We think that this new finding provides a basis for new tests for Crohn’s disease, with implications for both research and future treatments,” adds Dr van Heel, gastroenterologist at Hammersmith Hospital and Imperial College, who led the study.

Crohn’s disease affects between 30,000 and 60,000 people in the UK, with between 3,000 and 6,000 new cases diagnosed each year. The number of people with Crohn’s disease has been rising steadily, particularly among young people.

It can affect anywhere from the mouth to the anus but most commonly affects the small intestine and/or colon. It causes inflammation, deep ulcers and scarring to the wall of the intestine and often occurs in patches. The main symptoms are pain in the abdomen, urgent diarrhoea, general tiredness and loss of weight. Crohn’s is sometimes associated with other inflammatory conditions affecting the joints, skin and eyes.

"These results, although some way from providing clinical treatment, are extremely encouraging," comments Professor Subrata Ghosh, medical advisor to NACC - the National Association for Colitis and Crohn’s Disease, and one of the co-authors of the study. "In addition to helping patients with this faulty gene, we may find that patients without this particular genetic defect have similar disruptions to other parts of the NOD2/CARD15 system. Our hope is that this will lead to the identification of further genetic defects, and ultimately to new treatment strategies."

Simon Wilde | alfa
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