Kawasaki disease: update on pathogenesis

Purpose of review This review will highlight recent advances in our understanding of the pathogenesis of Kawasaki disease, highlighting the molecular players involved in regulation of T-cell activation and their affect on disease incidence and outcome in both humans and mouse. Recent findings Kawasaki disease is the most common cause of multisystem vasculitis in childhood. The vessels most commonly damaged are the coronary arteries, making Kawasaki disease the number one cause of acquired heart disease in children from the developed world. The contribution of genetics to disease predisposition is clearly implicated, but the mechanisms involved in regulating predisposition to disease susceptibility and outcome are not clearly understood. Two independent approaches have recently identified regulation of T-cell activation as the critical factor in determining susceptibility and severity of Kawasaki disease. Firstly, genetic analysis of affected Japanese children identified ITPKC, 1,4,5-triphosphate 3-kinase C, a kinase involved in regulation of T-cell activation, to be significantly associated with susceptibility to and increased severity of Kawasaki disease. A second independent approach using an animal model of Kawasaki disease has also identified regulation of T-cell activation, specifically costimulation, the second signal regulating optimal T-cell activation as the critical regulator of susceptibility to and severity of disease. Summary Understanding the molecular players responsible for dysregulation of the immune response in Kawasaki disease will foster development of improved diagnostic/predictive tools and more rational use of therapeutic agents to improve outcome in affected children.