Single-cell RNA sequencing of peripheral blood mononuclear cells from acute Kawasaki disease patients

Wang, Zhen; Xie, Lijian; Ding, Guohui; Song, Sirui; Chen, Liqin; Li, Guang; Xia, Min; Han, Dingding; Zheng, Yue; Liu, Jia; Xiao, Tingting; Zhang, Hong; Huang, Yujuan; Li, Yixue; Huang, Min

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. 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.