Activating KIR genes act as risk factors for Crohn’s Disease (93.34)

Abstract

Activating Killer-cell Immunoglobulin-like Receptor (KIR) genes constitute a subset of KIR family. The genes are expressed as activating receptors on the surface of NK cells as well as on a subset of T cells. The receptors interact with poorly defined ligands and decrease the activation threshold of these cells. Overall, they increase immune reactivity of the individuals. The activating KIR genes, like other KIR genes, are highly polymorphic. Furthermore, KIR haplotypes differ from each other with respect to the number of activating genes. Some haplotypes have no activating genes while others may carry upto seven such genes. Consequently, humans differ from each other with respect to the number of inherited activating KIR genes. Activating KIR genes have been associated with autoimmune diseases. However, little is known about their association with Crohn’s Disease. We have investigated the potential association of these genes with this disease in Canadian children of the French origin. Our results show that these genes act as risk factors for developing CD in these children. An increased number of inherited activating KIR genes correspondingly increased the risk for the disease. These results were also replicated in the Canadian (Caucasian) children of non-French origin. Collectively, our results suggest that activating KIR genes act as risk factors in developing CD in humans. The study was supported by the Crohn’s and Colitis Foundation of Canada (CCFC)