Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction

Nat Commun. 2021 Dec 10;12(1):7222. doi: 10.1038/s41467-021-27544-6.


Multi-system Inflammatory Syndrome in Children (MIS-C) is a major complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection 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. Here we perform a comprehensive analysis of the plasma proteome of more than 1400 proteins in children with SARS-CoV-2. We hypothesize that the proteome would reflect heterogeneity in hyperinflammation and vascular injury, and further identify pathogenic mediators of disease. We show that protein signatures demonstrate overlap between MIS-C, and the inflammatory syndromes macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). We demonstrate that PLA2G2A is an important marker of MIS-C that associates with TMA. We find that IFNγ responses are dysregulated in MIS-C patients, and that IFNγ levels delineate clinical heterogeneity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • COVID-19 / complications*
  • COVID-19 / metabolism
  • COVID-19 / pathology
  • Case-Control Studies
  • Chemokine CXCL9
  • Child
  • Endothelium, Vascular / physiopathology*
  • Group II Phospholipases A2
  • Humans
  • Inflammation
  • Interferon-gamma / immunology*
  • Interleukin-10
  • Proteome*
  • Proteomics
  • Systemic Inflammatory Response Syndrome / metabolism
  • Systemic Inflammatory Response Syndrome / pathology*
  • Vascular Diseases


  • Biomarkers
  • CXCL9 protein, human
  • Chemokine CXCL9
  • IL10 protein, human
  • Proteome
  • Interleukin-10
  • Interferon-gamma
  • Group II Phospholipases A2
  • PLA2G2A protein, human

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related