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- Title
Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction.
- Authors
Diorio, Caroline; Shraim, Rawan; Vella, Laura A.; Giles, Josephine R.; Baxter, Amy E.; Oldridge, Derek A.; Canna, Scott W.; Henrickson, Sarah E.; McNerney, Kevin O.; Balamuth, Frances; Burudpakdee, Chakkapong; Lee, Jessica; Leng, Tomas; Farrel, Alvin; Lambert, Michele P.; Sullivan, Kathleen E.; Wherry, E. John; Teachey, David T.; Bassiri, Hamid; Behrens, Edward M.
- 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. Multi-inflammatory syndrome in children (MIS-C) can be associated with SARS-CoV-2 infection but can also be similar to other inflammatory syndromes. Here the authors characterise the plasma proteome phenotype in MIS-C and compare to other SARS-CoV-2 related syndromes and find disproportionately high IFN-γ responses in MIS-C patients.
- Subjects
MULTISYSTEM inflammatory syndrome in children; INTERFERON gamma; MACROPHAGE activation syndrome; ENDOTHELIUM diseases; SYNDROMES in children
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-27544-6