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

Caroline Diorio, Rawan Shraim, Laura A. Vella, Josephine R. Giles, Amy E. Baxter, Derek A. Oldridge, Scott W. Canna, Sarah E. Henrickson, Kevin O. McNerney, Frances Balamuth, Chakkapong Burudpakdee, Jessica Lee, Tomas Leng, Alvin Farrel, Michele P. Lambert, Kathleen E. Sullivan, E. John Wherry, David T. Teachey (), Hamid Bassiri and Edward M. Behrens
Additional contact information
Caroline Diorio: University of Pennsylvania Perelman School of Medicine
Rawan Shraim: University of Pennsylvania Perelman School of Medicine
Laura A. Vella: University of Pennsylvania Perelman School of Medicine
Josephine R. Giles: University of Pennsylvania Perelman School of Medicine
Amy E. Baxter: University of Pennsylvania Perelman School of Medicine
Derek A. Oldridge: University of Pennsylvania Perelman School of Medicine
Scott W. Canna: University of Pennsylvania Perelman School of Medicine
Sarah E. Henrickson: University of Pennsylvania Perelman School of Medicine
Kevin O. McNerney: University of Pennsylvania Perelman School of Medicine
Frances Balamuth: University of Pennsylvania Perelman School of Medicine
Chakkapong Burudpakdee: University of Pennsylvania Perelman School of Medicine
Jessica Lee: University of Pennsylvania Perelman School of Medicine
Tomas Leng: University of Pennsylvania Perelman School of Medicine
Alvin Farrel: University of Pennsylvania Perelman School of Medicine
Michele P. Lambert: University of Pennsylvania Perelman School of Medicine
Kathleen E. Sullivan: University of Pennsylvania Perelman School of Medicine
E. John Wherry: University of Pennsylvania Perelman School of Medicine
David T. Teachey: University of Pennsylvania Perelman School of Medicine
Hamid Bassiri: University of Pennsylvania Perelman School of Medicine
Edward M. Behrens: University of Pennsylvania Perelman School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-27544-6

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