Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Ramaswamy et al. 2021 Supplementary Tables

Published: 7 April 2021| Version 3 | DOI: 10.17632/v9dkw64s6c.3
Contributor:
Anjali Ramaswamy

Description

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.

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Steps to reproduce

The CITE-seq panel is a custom list of 189 antibodies to surface markers. The differential gene expression data was produced using single-cell analysis workflow outlined in STAR methods. Data objects and steps to reproduce differential gene expression results are available at FASTgenomics.

Institutions

Yale University School of Medicine, Loma Linda University

Categories

Health Sciences

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