NGFN Research Team Discovers First Susceptibility Gene for Crohn's Disease

Recently, a NGFN research team headed by Prof. Stefan Schreiber identified the first traceable gene for Crohn's Disease, a chronic inflammatory bowel disease which frequently begins in young adulthood and then torments affected people for the rest of their lives. The main symptoms are usually bloody diarrhoea, severe abdominal pain, fever and fatigue.

By analyzing blood samples from more than 550 patients suffering inflammatory bowel disease Prof. Schreiber and his team identified a gene that confers susceptibility to Crohn's disease. This gene - called NOD2 - codes for a small protein that is found in certain cells of the host defense system in the intestine.
These so-called Monocytes and stimulated intestinal epithelial cells provide the first line of defense against pathogens by detecting and killing invading bacteria. NOD2 recognizes the bacterial component lipopolysaccharide.

Mutations of the NOD2 gene occuring in Crohn's disease patients cause a truncation of the NOD2 protein. This leads to a decreased response to bacterial lipopolysaccharides and defective signalling cascades. As a consequence the invasive bacteria are not eliminated. The failure of this first line of defense probably leads to an adaptation of the defense strategy against these bacteria. A second line of defense is generated by maturation of another set of immune cells, the so-called T-cells. In some individuals these adaptive immune cells trigger an abnormally high production of defensive cells and molecules, that not only kill the invading bacteria but also damage the surrounding tissue of the intestine and the harmless intestinal flora. This leads to relapsing inflammatory disorders.

Prof. Schreiber and his team found that beside of NOD2 there are additional disease-genes in inflammatory bowel disease. Furthermore environmental factors, e.g. nutritional habits or hygiene, either trigger or modify the risk for and course of Crohn's disease in the presence of genetic susceptibility. Since its first occurrence in 1920 the incidence of this inflammatory bowel diseased raised dramatically. Currently the Crohn's disease affects one out of 400 adults in north-western industrialised nations.

Numerous important collaborators were involved in this research such as the Guy's, King's and St. Thomas's Hospital in London, The BMBF network on Inflammatory Bowel Diseases (IBD) and the nationwide patient organisation DCCV (German Crohn´s & Ulcerative Colitis Foundation). These results were recently published in several renowned scientific journals including "Lancet" (Volume 357, issue 9272, pages 1925-1028), "Proceedings of the National Academy of Sciences" (Volume 99, issue 1, p 321 - 326), "European Journal of Human Genetics" (Volume 10, Nr. 4, pages 259-265) and "American Journal of Human Genetics" (Volume 72, Nr. 4, pages 1018-22).