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

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

doi:10.1038/s41467-021-25771-5

Abstract

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.

Highlights

Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries
IL-1β and tumor necrosis factor (TNF) are crucial inflammatory mediators during the pathogenesis of KD and have been used as therapeutic targets to treat intravenous immunoglobulin (IVIG)-resistant patients[37]. We found that both IL1B and TNF were mainly expressed in monocytes among peripheral blood mononuclear cells (PBMCs) and were upregulated in pre-treatment KD patients (Fig. 3d)
Discussion great efforts have been made in the research and treatment of KD, many essential questions remain to be clarified, such as what trigger the disease, how the coronary artery lesions (CALs) is developed and the mechanism of IVIG therapy

Summary

Introduction

Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. 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. 9 Collaborative Innovation Center for Genetics and Kawasaki disease (KD) is an acute, systemic febrile illness and vasculitis of childhood that can lead to coronary artery lesions (CALs)[1]. This disease predominantly affects children who are younger than 5 years and has become the most common cause of acquired heart disease among children in many developed countries[2].

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Conclusion