Kawasaki disease (KD) is a childhood vasculitis disease that is difficult to diagnose, and there is an urgent need for the identification of accurate and specific biomarkers. Here, we aimed to investigate metabolic alterations in patients with KD to determine novel diagnostic and prognostic biomarkers for KD. To this end, we performed untargeted metabolomics and found that several metabolic pathways were significantly enriched, including amino acid, lipid, and tryptophan metabolism, the latter of which we focused on particularly. Tryptophan-targeted metabolomics was conducted to explore the role of tryptophan metabolism in KD. The results showed that Trp and indole acetic acid (IAA) levels markedly decreased, and that l-kynurenine (Kyn) and kynurenic acid (Kyna) levels were considerably higher in patients with KD than in healthy controls. Changes in Trp, IAA, Kyn, and Kyna levels in a KD coronary arteritis mouse model were consistent with those in patients with KD. We further analyzed public single-cell RNA sequencing data of patients with KD and revealed that their peripheral blood mononuclear cells showed Aryl hydrocarbon receptor expression that was remarkably higher than that of healthy children. These results suggest that the Trp metabolic pathway is significantly altered in KD and that metabolic indicators may serve as novel diagnostic and therapeutic biomarkers for KD.

中文翻译：

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代谢分析揭示川崎病患者色氨酸代谢的改变

川崎病（KD）是一种难以诊断的儿童血管炎疾病，迫切需要鉴定准确且特异的生物标志物。在这里，我们的目的是研究川崎病患者的代谢变化，以确定川崎病的新诊断和预后生物标志物。为此，我们进行了非靶向代谢组学，发现几个代谢途径显着富集，包括氨基酸、脂质和色氨酸代谢，我们特别关注后者。以色氨酸为靶点的代谢组学研究了色氨酸代谢在川崎病中的作用。结果显示色氨酸和吲哚乙酸（IAA）水平显着下降，并且我川崎病患者中的犬尿氨酸 (Kyn) 和犬尿酸 (Kyna) 水平显着高于健康对照者。KD 冠状动脉炎小鼠模型中 Trp、IAA、Kyn 和 Kyna 水平的变化与 KD 患者的变化一致。我们进一步分析了川崎病患者的公开单细胞RNA测序数据，发现他们的外周血单个核细胞的芳烃受体表达量明显高于健康儿童。这些结果表明色氨酸代谢途径在川崎病中显着改变，代谢指标可以作为川崎病的新型诊断和治疗生物标志物。