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Platelets in Kawasaki disease: mediators of vascular inflammation

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From Nature Reviews Rheumatology

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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.

Key points

  • Platelets are essential for haemostasis and thrombosis; however, platelets also have multifaceted roles in regulating immune responses and contributing to the pathogenesis of inflammatory diseases.

  • Thrombocytosis is usually reported in Kawasaki disease, a systemic paediatric vasculitis, and has been associated with increased risk of developing coronary artery aneurysms.

  • Levels of monocyte–platelet aggregates (MPAs) and neutrophil–platelet aggregates (NPAs) increase during Kawasaki disease; these leukocyte–platelet aggregates (LPAs) might amplify Kawasaki disease pathogenesis through their pro-inflammatory and thrombotic functions and have been related to the development of coronary artery aneurysms in Kawasaki disease.

  • Although aspirin therapy does not reduce MPA formation, studies suggest that targeting the P-selectin–PSGL1 axis or inhibiting the P2Y12 receptor might attenuate platelet-induced monocyte activation.

  • Platelets are active participants and mediators of cardiovascular inflammation during Kawasaki disease vasculitis, not innocent bystanders. Hence, platelets might be promising therapeutic targets for Kawasaki disease vasculitis.

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Fig. 1: Pathophysiology and immune responses of Kawasaki disease.
Fig. 2: Platelets boost IL-1 inflammation and cardiovascular diseases.
Fig. 3: Antiplatelet therapy and Kawasaki disease.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Pediatric Infectious Diseases, Guerin Children’s, Cedars Sinai Medical Center, Los Angeles, CA, USA

    Magali Noval Rivas & Moshe Arditi

  2. Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Magali Noval Rivas & Moshe Arditi

  3. Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey

    Begüm Kocatürk

  4. Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany

    Bernardo S. Franklin

  5. Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Moshe Arditi

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Noval Rivas, M., Kocatürk, B., Franklin, B.S. et al. Platelets in Kawasaki disease: mediators of vascular inflammation. Nat Rev Rheumatol 20, 459–472 (2024). https://doi.org/10.1038/s41584-024-01119-3

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