Genetic cause of inflammatory bowel disease

Links: UCL researchers were part of the team to discover that mutations in either of two related genes can cause a severe form of inflammatory bowel disease (IBD) in young children. Erik Glocker (UCL Infection & Immunity) said: 'This discovery is a milestone in research on inflammatory bowel disease, and will enable us to gain further insights into the physiology and immunity of the intestine.' Glocker found the first mutation in the protein IL10R2 identified in the study. Analysis of additional patients with early onset colitis revealed mutations in IL10R1. IL10 plays a crucial role in keeping the body's inflammatory responses in check. The human body is continually generating local inflammatory responses to control microbial infections and to repair damage from toxins, but if that inflammatory response is not properly controlled tissues may be excessively damaged. When either IL10R1 or IL10R2 is mutated, the signals from IL10 cannot be received, and the resulting inflammation causes tissue damage, especially in the gastrointestinal system. The gene identification effort was led by Professor Bodo Grimbacher at UCL Medical School (Royal Free Campus Hampstead), and head of the Marie-Curie Excellence Research Group, who said: 'This discovery will lead to future therapeutic options not only in children but potentially also in adult patients with IL10 signalling problems.' Other research groups focusing primarily on adult-onset IBD have identified dozens of genes and variants that affect the risk for IBD, but this is the first study to show that a single genetic mutation is sufficient to cause the disease.