Proteomic Profiling of MIS-C Patients Reveals Heterogeneity Relating to Interferon Gamma Dysregulation and Vascular Endothelial Dysfunction.

TitleProteomic Profiling of MIS-C Patients Reveals Heterogeneity Relating to Interferon Gamma Dysregulation and Vascular Endothelial Dysfunction.
Publication TypeJournal Article
Year of Publication2021
AuthorsDiorio C, Shraim R, Vella LA, Giles JR, Baxter AE, Oldridge DA, Canna SW, Henrickson SE, McNerney KO, Balamuth F, Burudpakdee C, Lee J, Leng T, Farrell A, Lambert MP, Sullivan KE, E Wherry J, Teachey DT, Bassiri H, Behrens EM
JournalmedRxiv
Date Published2021 Apr 20
Abstract

Multi-system Inflammatory Syndrome in Children (MIS-C) is a major complication of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic in pediatric patients. Weeks after an often mild or asymptomatic initial infection with SARS-CoV-2 children may present with a severe shock-like picture and marked inflammation. Children with MIS-C present with varying degrees of cardiovascular and hyperinflammatory symptoms. We performed a comprehensive analysis of the plasma proteome of more than 1400 proteins in children with SARS-CoV-2. We hypothesized that the proteome would reflect heterogeneity in hyperinflammation and vascular injury, and further identify pathogenic mediators of disease. Protein signatures demonstrated overlap between MIS-C, and the inflammatory syndromes macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). We demonstrate that PLA2G2A is a key marker of MIS-C that associates with TMA. We found that IFNγ responses are dysregulated in MIS-C patients, and that IFNγ levels delineate clinical heterogeneity.

DOI10.1101/2021.04.13.21255439
Alternate JournalmedRxiv
PubMed ID33907759
PubMed Central IDPMC8077582