Atici Asli Ekin, Noval Rivas Magali, Arditi Moshe
Division of Infectious Diseases and Immunology, Department of Pediatrics, Guerin Children's at Cedars-Sinai Medical Center, Los Angeles, California, USA; Infectious and Immunologic Diseases Research Center, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Division of Infectious Diseases and Immunology, Department of Pediatrics, Guerin Children's at Cedars-Sinai Medical Center, Los Angeles, California, USA; Infectious and Immunologic Diseases Research Center, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Can J Cardiol. 2024 Dec;40(12):2305-2320. doi: 10.1016/j.cjca.2024.07.023. Epub 2024 Jul 30.
Kawasaki disease (KD) manifests as an acute febrile condition and systemic vasculitis, the etiology of which remains elusive. Primarily affecting children under 5 years of age, if untreated KD can lead to a significant risk of coronary artery aneurysms and subsequent long-term cardiovascular sequelae, including myocardial ischemia and myocardial infarction. Intravenous immunoglobulin therapy mitigates the risk of aneurysm formation, but a subset of patients exhibit resistance to this treatment, increasing the susceptibility of coronary artery lesions. Furthermore, the absence of a KD-specific diagnostic test or biomarkers complicates early detection and appropriate treatment. Experimental murine models of KD vasculitis have substantially improved our understanding of the disease pathophysiology, revealing the key roles of the NLRP3 inflammasome and interleukin-1 (IL-1) signalling pathway. This review aims to delineate the pathophysiologic findings of KD while summarising the findings for the emerging key role of IL-1β in its pathogenesis, derived from both human data and experimental murine models, and the translational potential of these findings for anti-IL-1 therapies for children with KD.
川崎病（KD）表现为急性发热病症和全身性血管炎，其病因仍不明晰。主要影响5岁以下儿童，若不治疗，KD会导致冠状动脉瘤形成以及后续长期心血管后遗症的重大风险，包括心肌缺血和心肌梗死。静脉注射免疫球蛋白疗法可降低动脉瘤形成的风险，但一部分患者对这种治疗表现出抗性，增加了冠状动脉病变的易感性。此外，缺乏KD特异性诊断测试或生物标志物使早期检测和恰当治疗变得复杂。KD血管炎的实验小鼠模型极大地增进了我们对该疾病病理生理学的理解，揭示了NLRP3炎性小体和白细胞介素-1（IL-1）信号通路的关键作用。本综述旨在阐述KD的病理生理学发现，同时总结来自人类数据和实验小鼠模型的关于IL-1β在其发病机制中新兴关键作用的发现，以及这些发现对KD患儿抗IL-1疗法的转化潜力。
