Delineation of Single-cell Altas Provides New Insights for Development of Coronary Artery Lesions in Kawasaki Disease: Bad and Good Signaling Molecules

Abstract

BackgroundKawasaki Disease (KD) is a vasculitis syndrome featured with a high and persistent fever and mainly affects children under 5 years of age. It is the leading cause of acquired heart disease in the form of coronary artery lesions (CALs) for children in developed countries. Most KD can be relieved with the high-dosage Intravenous immunoglobulin (IVIG) therapy, but a small proportion develop CALs after IVIG treatment. MethodsWe performed the single-cell RNA sequencing for the peripheral blood mononuclear cells (PBMCs) from three KD non-CAL patients whose samples were acquired before and after IVIG treatment and three KD CAL patients whose samples were acquired only after IVIG treatment. Cell-to-cell communication patterns were also analyzed in KD CAL and non-CAL patients ResultsOverall cell expression feature analyses show immunoglobulin and adaptive immunity related genes are upregulated in KD CAL patients while B cell activation related genes are downregulated in them. Pseudo-time analyses demonstrate that both KD non-CAL patients before treatment and KD CAL patients after treatment have a dysregulated B cell developmental trajectory while the former has a mixed T and B lineage and the latter has a mixed monocyte and B lineage. The early elevated expression of SPI1 could partly explain the dysregulated B cell development in KD CAL patients. Cell communication analyses propose a disorder cell communication pattern in KD non-CAL patients before treatment and some persistent bad cell-to-cell signals in KD CAL patients after treatment. There are four signaling molecules, APP, CCL, and MCH-II, whose expression is significantly increased in the CD14 and CD16 monocytes of KD CAL patients, where the expression of RESISTIN is significantly increased in those KD non-CAL patients. ConclusionsOur results suggest that APP, CCL, and MCH-II might be the bad signals for indicating the possible development of CAL while RESISTIN is a good one for protecting from CAL.