Table 5_CD14+ monocytes: the immune communication hub in early vasculitis symptoms of Kawasaki disease.xlsx

BackgroundKawasaki Disease (KD) is an acute systemic vasculitis syndrome predominantly affecting children, with a propensity to induce coronary artery lesions. Aberrant immune activation and cytokines cascade reactions are involved in its pathogenesis. The aim of this study is to investigate the changes in immune cell communication during the course of KD and to identify potential biomarkers.
MethodsThe study enrolled seven pediatric patients diagnosed with Kawasaki Disease (KD) between December 2019 and December 2021. Single-cell RNA sequencing (scRNA-seq) technology was utilized to analyze peripheral blood mononuclear cells (PBMCs). Bioinformatics methods including quality control, dimensionality reduction, cell annotation, differential expression analysis, cell communication analysis, and co-expression network analysis were employed for data processing and analysis.
ResultsThis study utilized single-cell sequencing technology to uncover the dynamics of immune cell communication during the course of KD, revealing a significant increase in the number of CD14+ monocytes in the early stages of vasculitis, which play a central role in cell-cell communication. SELPLG was identified as a particularly crucial gene in the signal transduction among immune cells. The study also observed various cellular communication patterns of vasculitis at different time points and identified co-expression modules related to ribosomal function, cell proliferation, and immune responses in CD19+ B cells, CD4+ T cells, CD8+ T cells, CD14+ monocytes, and CD16+ monocytes. Notably, the expression of the ITK gene in CD14+ monocytes stood out. Furthermore, MHC-I genes were the most active molecules involved in signal transduction, and the expression of CD40 genes increased with the prolongation of vasculitis duration.
ConclusionCD14+ monocytes play a pivotal role in cellular communication during the activation process of KD vasculitis, with SELPLG and ITK as important communication signal genes. These findings provide a novel perspective for the discovery of biomarkers, prediction of disease progression, and the development of targeted treatment strategies for KD.
Clinical Trial Registrationhttp://www.medresman.org.cn/pub/cn/proj/projectshow.aspx?proj=7739, identifier ChiCTR, ChiCTR2100044729.

背景 川崎病（Kawasaki Disease, KD）是一种主要累及儿童的急性全身性血管炎综合征，易诱发冠状动脉病变。其发病机制涉及异常免疫激活与细胞因子级联反应。本研究旨在探讨KD病程中免疫细胞通讯的动态变化，并鉴定潜在生物标志物。
方法 本研究纳入2019年12月至2021年12月期间确诊的7例川崎病患儿。采用单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）技术对外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）进行分析。通过质控、降维、细胞注释、差异表达分析、细胞通讯分析及共表达网络分析等生物信息学方法完成数据处理与分析。
结果 本研究借助单细胞测序技术揭示了KD病程中免疫细胞通讯的动态变化，发现血管炎早期CD14+单核细胞数量显著升高，且在细胞间通讯中发挥核心作用。鉴定出SELPLG是免疫细胞信号转导过程中尤为关键的基因。研究同时观察到不同时间点血管炎的多种细胞通讯模式，并在CD19+B细胞、CD4+T细胞、CD8+T细胞、CD14+单核细胞及CD16+单核细胞中鉴定出与核糖体功能、细胞增殖及免疫应答相关的共表达模块。值得注意的是，ITK基因在CD14+单核细胞中的表达尤为突出。此外，主要组织相容性复合体I类（MHC-I）基因是参与信号转导最活跃的分子，且CD40基因的表达随血管炎病程延长而升高。
结论 CD14+单核细胞在KD血管炎激活过程的细胞通讯中发挥关键作用，SELPLG与ITK为重要的通讯信号基因。本研究结果为KD的生物标志物发现、疾病进展预测及靶向治疗策略开发提供了全新视角。
临床试验注册 http://www.medresman.org.cn/pub/cn/proj/projectshow.aspx?proj=7739，注册号为ChiCTR, ChiCTR2100044729。