Kawasaki disease: pathophysiology and insights from mouse models

Kawasaki disease is an acute febrile illness and systemic vasculitis of unknown aetiology that predominantly afflicts young children, causes coronary artery aneurysms and can result in long-term cardiovascular sequelae. Kawasaki disease is the leading cause of acquired heart disease among children in the USA. Coronary artery aneurysms develop in some untreated children with Kawasaki disease, leading to ischaemic heart disease and myocardial infarction. Although intravenous immunoglobulin (IVIG) treatment reduces the risk of development of coronary artery aneurysms, some children have IVIG-resistant Kawasaki disease and are at increased risk of developing coronary artery damage. In addition, the lack of specific diagnostic tests and biomarkers for Kawasaki disease make early diagnosis and treatment challenging. The use of experimental mouse models of Kawasaki disease vasculitis has considerably improved our understanding of the pathology of the disease and helped characterize the cellular and molecular immune mechanisms contributing to cardiovascular complications, in turn leading to the development of innovative therapeutic approaches. Here, we outline the pathophysiology of Kawasaki disease and summarize and discuss the progress gained from experimental mouse models and their potential therapeutic translation to human disease. This Review outlines the pathophysiology of Kawasaki disease and discusses the progress gained from experimental mouse models and their potential therapeutic translation to human disease. Key pointsKawasaki disease is a childhood systemic vasculitis leading to the development of coronary artery aneurysms; it is the leading cause of acquired heart disease in children in developed countries.The cause of Kawasaki disease is unknown, although it is suspected to be triggered by an unidentified infectious pathogen in genetically predisposed children.Kawasaki disease might not be a normal immune response to an unusual environmental stimulus, but rather a genetically determined unusual and uncontrolled immune response to a common stimulus.Although the aetiological agent in humans is unknown, mouse models of Kawasaki disease vasculitis demonstrate similar pathological features and have substantially accelerated discoveries in the field.Genetic and transcriptomic analysis of blood samples from patients with Kawasaki disease and experimental evidence generated using mouse models have demonstrated the critical role of IL-1 beta in the pathogenesis of this disease and the therapeutic potential of targeting this pathway (currently under investigation in clinical trials).