Hara Toshiro, Sakai Yasunari
Reiwa Health Sciences University, Fukuoka, Japan.
Kawasaki Disease Center, Fukuoka Children's Hospital, Fukuoka, Japan.
Immun Inflamm Dis. 2025 Sep;13(9):e70267. doi: 10.1002/iid3.70267.
Kawasaki disease (KD) is a leading cause of acquired heart disease in children. Evidence suggests that microbial and nonmicrobial triggers for KD differ across geographical regions and environmental conditions. Although the precise triggers remain unidentified, KD is likely caused by microbial or environmental agents acting on genetically predisposed children.
Insights into KD pathogenesis have also been derived from three well-established murine models, which highlight diverse vasculitis-inducing pathways. The diversity of microbial triggers supports the hypothesis that KD arises from immune-mediated responses rather than direct infection. Pathogen-associated molecular patterns (PAMPs), microbe-associated molecular patterns (MAMPs) and inflammatory cell death-linked damage-associated molecular patterns (DAMPs) play critical roles in KD pathogenesis. Furthermore, genetic polymorphisms associated with KD, such as ITPKC, CASP3, and FCGR2A, contribute to immune activation by promoting inflammasome activation, pyroptosis and antibody-dependent enhancement (ADE), thereby intensifying inflammation. Oxidative and nitrative stress further amplify inflammatory responses, with their interplay potentially driving KD onset. The relatively low recurrence rate of KD, despite its diverse triggers, may partly be explained by the presence of anti-DAMP antibodies. Historically, reduced exposure to infections and improved sanitation may have led to lower levels of anti-DAMP antibodies, potentially contributing to the increased incidence of KD observed over time.
Continued research into microbial and immune mechanisms is crucial to advance our understanding of KD pathogenesis.
川崎病（KD）是儿童后天性心脏病的主要病因。有证据表明，KD的微生物和非微生物触发因素因地理区域和环境条件而异。尽管确切的触发因素仍未明确，但KD可能是由作用于具有遗传易感性儿童的微生物或环境因素引起的。
对KD发病机制的深入了解也来自于三种成熟的小鼠模型，这些模型突出了不同的血管炎诱导途径。微生物触发因素的多样性支持了KD源于免疫介导反应而非直接感染的假说。病原体相关分子模式（PAMPs）、微生物相关分子模式（MAMPs）以及与炎症细胞死亡相关的损伤相关分子模式（DAMPs）在KD发病机制中起关键作用。此外，与KD相关的基因多态性，如ITPKC、CASP3和FCGR2A，通过促进炎性小体激活、细胞焦亡和抗体依赖性增强（ADE）来促进免疫激活，从而加剧炎症。氧化应激和硝化应激进一步放大炎症反应，它们之间的相互作用可能推动KD的发病。尽管KD有多种触发因素，但其相对较低的复发率可能部分归因于抗DAMP抗体的存在。从历史上看，感染暴露减少和卫生条件改善可能导致抗DAMP抗体水平降低，这可能是导致KD发病率随时间增加的原因之一。
持续研究微生物和免疫机制对于增进我们对KD发病机制的理解至关重要。
