Platelets in Kawasaki disease: mediators of vascular inflammation

Abstract

Kawasaki disease, a systemic vasculitis that affects young children and can result in coronary artery aneurysms, is the leading cause of acquired heart disease among children. A hallmark of Kawasaki disease is increased blood platelet counts and platelet activation, which is associated with an increased risk of developing resistance to intravenous immunoglobulin and coronary artery aneurysms. Platelets and their releasate, including granules, microparticles, microRNAs and transcription factors, can influence innate immunity, enhance inflammation and contribute to vascular remodelling. Growing evidence indicates that platelets also interact with immune and non-immune cells to regulate inflammation. Platelets boost NLRP3 inflammasome activation and IL-1β production by human immune cells by releasing soluble mediators. Activated platelets form aggregates with leukocytes, such as monocytes and neutrophils, enhancing numerous functions of these cells and promoting thrombosis and inflammation. Leukocyte–platelet aggregates are increased in children with Kawasaki disease during the acute phase of the disease and can be used as biomarkers for disease severity. Here we review the role of platelets in Kawasaki disease and discuss progress in understanding the immune-effector role of platelets in amplifying inflammation related to Kawasaki disease vasculitis and therapeutic strategies targeting platelets or platelet-derived molecules. This Review outlines the role of platelets in Kawasaki disease and the immune-effector role of platelets in amplifying inflammation related to Kawasaki disease vasculitis and highlights therapeutic strategies that target platelets or platelet-derived molecules.