Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. Although functional and phenotypic changes of immune cells have been reported, a global understanding of immune responses underlying acute KD is unclear. Here, using single-cell RNA sequencing, we profile peripheral blood mononuclear cells from seven patients with acute KD before and after intravenous immunoglobulin therapy and from three age-matched healthy controls. The most differentially expressed genes are identified in monocytes, with high expression of pro-inflammatory mediators, immunoglobulin receptors and low expression of MHC class II genes in acute KD. Single-cell RNA sequencing and flow cytometry analyses, of cells from an additional 16 KD patients, show that although the percentage of total B cells is substantially decreased after therapy, the percentage of plasma cells among the B cells is significantly increased.
FIG: Two-dimensional representation of cell types identified by scRNA-seq: The dimensional reduction is performed with the uniform manifold approximation and projection (UMAP). Each dot represents a cell, which is colored according to cell type. The cells are pooled across all patients and separated by conditions: a KD before intravenous immunoglobulin (IVIG) therapy; b KD after IVIG therapy; c healthy controls. Percentages of major cell types under each condition are shown on the plot, and percentages of subtypes are shown on Supplementary Fig. mDC, myeloid dendritic cells; pDC, plasmacytoid dendritic cells; HSPC, hematopoietic stem and progenitor cells. Source data are provided in the Source Data file.
The percentage of CD8+ T cells is decreased in acute KD, notably effector memory CD8+ T cells compared with healthy controls. Oligoclonal expansions of both B cell receptors and T cell receptors are observed after therapy. We identify biological processes potentially underlying the changes of each cell type. The single-cell landscape of both innate and adaptive immune responses provides insights into pathogenesis and therapy of KD.
Wang, Z., Xie, L., Ding, G. et al. Single-cell RNA sequencing of peripheral blood mononuclear cells from acute Kawasaki disease patients. Nat Commun 12, 5444 (2021). https://doi.org/10.1038/s41467-021-25771-5