Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children

Area of Science:

• Molecular Biology
• Immunology
• Pediatric Cardiology

Background:

• Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) are pediatric inflammatory conditions with overlapping symptoms but distinct cardiovascular outcomes.
• Endothelial cells (ECs) play a crucial role in cardiovascular health and may be differentially affected in KD and MIS-C, contributing to varied clinical trajectories.

Purpose of the Study:

• To investigate the differential molecular responses of endothelial cells (ECs) exposed to sera from patients with MIS-C versus KD.
• To identify specific gene expression patterns and pathways in ECs that distinguish MIS-C from KD, potentially explaining differences in cardiovascular complications.

Main Methods:

• RNA sequencing (RNA-seq) was performed on cultured human ECs incubated with pre-treatment sera from MIS-C, KD, and healthy control cohorts.
• Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis were employed to identify key molecular pathways and transcripts.

Main Results:

• MIS-C sera induced significant upregulation of TNFα/NFκB pathway genes, pro-survival transcripts, and autophagy-related genes (UBD, EBI3, SQSTM1) in ECs.
• Conversely, KD sera were associated with decreased EC homeostasis and endothelial-mesenchymal transition (EndoMT) related transcripts compared to MIS-C.
• WGCNA identified seven distinct gene modules in MIS-C, highlighting altered immune responses, EC homeostasis, and EndoMT.

Conclusions:

• Endothelial cells exhibit distinct transcriptomic profiles when exposed to MIS-C versus KD sera, characterized by increased pro-survival signaling in MIS-C.
• The observed differences in EC responses, including altered homeostasis and EndoMT, may underlie the divergent cardiovascular sequelae observed in MIS-C and KD.