Background: Kawasaki 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.Methods: The 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.Results: This 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.Conclusion: CD14+ 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 Registration: http://www.medresman.org.cn/pub/cn/proj/projectshow.aspx?proj=7739, identifier ChiCTR, ChiCTR2100044729.
Background: Kawasaki disease (KD), an acute vasculitis syndrome affecting children under 5 years, lacks specific biological markers for diagnosis. This study explores immune cell activation in KD patients during early vasculitis symptoms to identify potential diagnostic markers and guide intravenous immunoglobulin (IVIG) therapy timing. Methods: The study included single-cell sequencing (SCS) from 10 patients, comprising seven with KD and three controls, as well as flow cytometry and polymerase chain reaction (PCR) validation from 277 patients. This included 95 children with KD and controls consisting of 12 healthy children and 170 children with febrile illnesses. Children with KD were divided into early vasculitis group and late vasculitis group based on whether the symptoms of vasculitis were less than or more than three days. peripheral blood mononuclear cells (PBMCs) were sequenced using the 10× Genomics platform, and flow cytometry and quantitative PCR (qPCR) verified changes in gene expression and cell proportions. Results: KD patients showed higher CD19+ B cells, particularly in the late vasculitis group. Pre-treatment CD19+ B cells were elevated and normalized post-IVIG treatment. Flow cytometry validation confirmed the increase in CD19+ B cells before IVIG treatment, which decreased to normal levels post-treatment, aligning with the SCS results. The study identified a total of 1,680 differentially expressed genes (DEGs) involved in B cell activation and immune responses, with core genes like IFITM1, CD55, FCER1G, and others down-regulated in the late vasculitis group. Time-series analysis revealed genes with high expression in early vasculitis that down-regulated over time, including S100A8, S100A9, and S100A12 which were further validated using qPCR, showing higher expression in the early stage of KD compared to healthy controls. Conclusions: This study highlights the close relationship between the number of immune cells and gene expression changes with the duration of vasculitis in KD, providing new insights into the pathophysiological mechanisms of the disease and potential prognostic indicators for clinical treatment.
Background: Kawasaki disease (KD), the most common acquired heart disease in children with rising global incidence, significantly increases risk for later allergic diseases. KD-asthma comorbidity escalates medical needs and treatment complexity, necessitating a deeper understanding of their relationship. Therefore, this study aimed to explore shared transcriptomic profiles, immune cell landscapes, and key susceptibility genes between pediatric KD and asthma through multi-omics integration. Methods: This study retrospectively analyzed allergic disease incidence in KD patients at the Department of Cardiology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, and recruited 13 KD-asthma children for single-cell RNA sequencing. Common susceptibility genes were identified through literature mining and differential analysis of public datasets. Bioinformatics methods explored immune cell landscapes, gene expression profiles, and functional characteristics. Results: Retrospective analysis of 222 pediatric KD patients revealed that 47.74% later developed allergic diseases. A systematic review of nearly 5,000 articles identified shared susceptibility genes significantly enriched in immune processes and signaling pathways. Single-cell RNA sequencing of 13 children showed distinct immune cell compositions and expression profiles versus controls. Both diseases exhibited enrichment of inflammatory and extracellular vesicle-related genes. Molecular function analysis showed that asthma differentially expressed genes primarily involved antigen binding and major histocompatibility complex (MHC) class II protein complex binding, while KD genes involved Toll-like receptor binding and calcium-dependent protein binding. Conclusions: This study suggests a potential immunological link between KD and subsequent allergic conditions. Shared susceptibility genes and transcriptomic profiles are significantly enriched in inflammatory and vesicle-related pathways, providing insights into the biological overlap between these conditions.
Early diagnosis of Kawasaki disease (KD) remains challenging, particularly in incomplete or early-stage cases, increasing the risk of coronary artery compl