Single-cell RNA sequencing of peripheral blood mononuclear cells

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).

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