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通过生物信息学探索川崎病中与铁死亡相关的免疫特征。

Exploring ferroptosis-associated immune characteristics in Kawasaki disease through bioinformatics.

作者信息

Li Wei, Duan Yan, Zhang Lingyun, Zou Jialin, Liu Bin, Jiang Jun, Liu Dong, Liu Haiyan, Li Gang

机构信息

Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Luzhou, Sichuan, China.

Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China.

出版信息

Sci Rep. 2025 Aug 18;15(1):30261. doi: 10.1038/s41598-025-15182-7.

Abstract

Kawasaki disease (KD), as a common pediatric inflammatory vasculitis, has an unclear pathogenesis. This study integrated bioinformatics and clinical data analysis to explore the characteristics of ferroptosis in KD. We used data from the Gene Expression Omnibus (GEO) database to identify ferroptosis-related genes, and variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) analysis. We employed seven machine learning methods to determine the optimal predictive model, revealing that the Support Vector Machine (SVM) model exhibited optimal performance in external validation. Unsupervised clustering based on FRGs stratified KD patients into high and low expression subtypes. The high expression subtype showed significantly elevated levels of monocyte immune infiltration, which was further validated by single-cell analysis. Clinical data analysis demonstrated that patients in the high-monocyte group not only had a higher incidence of incomplete KD presentations but also exhibited lower resistance to intravenous immunoglobulin (IVIG) therapy. These results suggest that ferroptosis may participate in the pathogenesis of KD by modulating monocyte levels, providing new insights into explaining clinical heterogeneity and differences in IVIG treatment responses.

摘要

川崎病(KD)作为一种常见的儿童炎性血管炎,其发病机制尚不清楚。本研究整合生物信息学和临床数据分析,以探讨KD中 ferroptosis 的特征。我们使用来自基因表达综合数据库(GEO)的数据来识别与ferroptosis相关的基因,并使用最小绝对收缩和选择算子(LASSO)分析进行变量选择。我们采用七种机器学习方法来确定最佳预测模型,结果显示支持向量机(SVM)模型在外部验证中表现出最佳性能。基于铁死亡相关基因(FRGs)的无监督聚类将KD患者分为高表达和低表达亚型。高表达亚型显示单核细胞免疫浸润水平显著升高,单细胞分析进一步验证了这一点。临床数据分析表明,高单核细胞组患者不仅不完全KD表现的发生率较高,而且对静脉注射免疫球蛋白(IVIG)治疗的抵抗力较低。这些结果表明,ferroptosis可能通过调节单核细胞水平参与KD的发病机制,为解释临床异质性和IVIG治疗反应差异提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd2d/12361573/7088ffa287fb/41598_2025_15182_Fig1_HTML.jpg

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