Project 174405

The overall objective of our team is to understand why the body damages the blood vessels in Kawasaki disease (KD) and to identify new biologic markers that will aid in identification of children at risk for disease and develop poor outcome. KD is the leading cause of acquired heart disease in Canadian children. An infection starts KD. In a healthy person the immune cells, especially the T-cells, turn off after successfully fighting the infection. In a person with KD the T-cells do not turn off, they keep going and attack the blood vessels supplying the heart, the coronary arteries. We have evidence from two independent approaches that molecules, which regulate T-cell activation, are the critical factors that determine how T-cells are turned on and stay turned on. This project will determine how (the mechanisms), who (the genes, molecules and cells) and why (the processes) these T-cells are activated, stay activated and attack the coronary arteries. We will accomplish this goal by examining the genes, proteins, cells, disease processes and outcome in KD. These goals will be elegantly linked by studies in both children with KD as well as an animal model of disease. Our work will challenge current theories of disease but more importantly will uncover improved diagnostic tools to enhance disease recognition and individualize treatment, providing a logical approach to improving therapy and outcome in affected children.