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

By 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, Edward M. Behrens

Posted 20 Apr 2021
medRxiv DOI: 10.1101/2021.04.13.21255439

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 IFN{gamma} responses are dysregulated in MIS-C patients, and that IFN{gamma} levels delineate clinical heterogeneity.

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