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: Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease causing right heart failure. Idiopathic PAH (IPAH), a type of PAH with unknown causes, has a particularly poor prognosis. Current targeted therapies are insufficient, highlighting the need for new therapeutic targets and biomarkers. This study aims to identify potential metabolic biomarkers and dysregulated pathways for the diagnosis and treatment of IPAH through integrated metabolomic and transcriptomic analyses. Methods: This study enrolled PAH patients [2023–2024] and collected pretreatment blood samples, using healthy children as controls. RNA sequencing analyzed gene expression in peripheral blood mononuclear cells (PBMCs), and liquid chromatography-mass spectrometry (LC-MS) detected blood metabolites. Metabolites were identified via multiple databases, and bioinformatics analyses [principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA)] explored PAH’s molecular mechanisms. Results: In PAH patients, 1,629 differentially expressed genes (DEGs) were found, with 802 upregulated and 827 downregulated genes, enriched in cell cycle regulation, stress response, and mitochondrial dysfunction. Metabolomics showed 30 upregulated and 29 downregulated metabolites, mainly in amino acid and energy metabolism. Key genes like LDHB and IRS2, and metabolites such as glucose and L-glutamine, are closely linked to PAH’s pathology, especially in glycolysis pathways. Conclusions: The study underscores the intimate connection between transcription factor (e.g., JUNB, ZNF281)-regulated gene expression (e.g., LDHB, IRS2) and metabolite (e.g., glucose, L-glutamine) alterations in PAH, revealing that key genes and metabolites closely tied to the disease’s pathology.

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

Background: Kawasaki disease (KD) is a pediatric systemic vasculitis in which T-cell-mediated immune responses play a pivotal role. However, the precise dynamic evolution of T-cell subsets during disease progression remains poorly understood. Methods: Single-cell RNA sequencing (scRNA-seq) was employed to perform high-resolution annotation of peripheral blood mononuclear cells (PBMCs) from healthy controls and KD patients, both pre- and post- IVIG treatment. T-cell developmental trajectories were reconstructed via Monocle3-based pseudotime analysis. Furthermore, the functional significance of the significant pathway was validated in a CAWS-induced KD murine model. Results: A high-resolution single-cell landscape identified 13 distinct T-cell subtypes. Pseudotime analysis revealed a significant lineage commitment of CD4 ⁺ T cells toward a Th17 phenotype during the acute phase of KD, synchronized with the transcriptional upregulation of the STAT3/JAK signaling axis. Animal experiments further demonstrated that pharmacological inhibition of this pathway substantially attenuated inflammatory infiltration in the cardiac vasculature of KD mice. Conclusion: This study identifies the STAT3/JAK-mediated Th17 differentiation bias as a potential regulatory program associated with acute inflammation in Kawasaki disease, thereby highlighting the STAT3/JAK axis as a potential therapeutic target.