Lay Summary

Proposal No.   IBD-0003R
Principal Investigator: Geoffrey W. Krissansen, Ph.D.
Applicant Organization:  University of Auckland (New Zealand)
Project Title:  Pattern recognition receptors as potential susceptibility loci for Crohn's disease
Period of Award:  November 1, 2002 – March 31, 2005

Crohn’s disease (CD) is a chronic inflammatory bowel disease affecting approximately 1 in 1000 people in developed countries.  The immune system attacks the digestive tract, causing abdominal pain, cramping, diarrhea, rectal bleeding, fever, and weight loss.  The prevailing theory is that the immune system in genetically susceptible individuals responds incorrectly to intestinal bacteria or viruses.  Recent research identified a gene that was damaged in approximately 15% of Crohn’s patients.  The NOD2 protein that is made from the NOD2 gene helps our immune systems to recognize and respond to bacteria, but the damaged NOD2 protein cannot do this correctly in CD patients.  NOD2 is but one of several proteins that allow our immune systems to recognize bacteria.

We will screen up to 100 CD families that show abnormal responses to bacteria to determine whether genes that make these other proteins are also damaged in CD patients.  We will develop a novel system to examine the effects that a damaged NOD2 gene has on the immune system.  Finally, we will determine whether introducing a normal NOD2 protein into damaged CD cells can restore their response to bacteria.  The project could lead to the discovery of new therapeutic and diagnostic targets, provide a model cell system to understand the disease process, and will provide information that will be critical in assessing therapeutic approaches to prevent or ameliorate CD.