Aberrant peripheral immune responses in acute Kawasaki disease with single-cell sequencing

Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. Although diverse immune aberrance was reported, a global understanding of immune responses underlying acute KD was lacking. Based on single-cell sequencing, we profiled peripheral blood mononuclear cells from patients with acute KD before and after intravenous immunoglobulin therapy and from healthy controls. Most differentially expressed genes were derived from monocytes, with upregulation of immunoglobulin receptors, complement and receptors and downregulation of MHC class II receptors before therapy. The percentage of B cells was significantly increased before therapy and rapidly returned to normal after therapy. There was also an increased abundance of B-cell receptors with IGHA and IGHG after therapy, accompanied by massive oligoclonal expansion. The percentage of CD8 T cells was remarkably decreased during acute KD, especially the subset of effector memory CD8 T cells. All lymphocyte compartments were characterized by underexpressed interferon response pathways before therapy. The identification of unique innate and adaptive immune responses suggests potential mechanisms underlying pathogenesis and progression of KD.

川崎病（KD）是发达国家儿童获得性心脏病最常见的病因。尽管有多种免疫异常的报道，但对急性川崎病潜在的免疫反应缺乏全面的了解。基于单细胞测序，我们对急性川崎病患者在静脉注射免疫球蛋白治疗前后以及健康对照者的外周血单个核细胞进行了分析。大多数差异表达基因来自单核细胞，治疗前免疫球蛋白受体、补体及其受体上调，MHC II类受体下调。B细胞百分比在治疗前显著增加，治疗后迅速恢复正常。治疗后带有IGHA和IGHG的B细胞受体丰度也增加，同时伴有大量寡克隆扩增。在急性川崎病期间，CD8 T细胞百分比显著降低，尤其是效应记忆CD8 T细胞亚群。治疗前所有淋巴细胞亚群的特征是干扰素反应通路表达不足。独特的先天性和适应性免疫反应的确定提示了川崎病发病机制和进展的潜在机制。