tetano
Editor, Senior Moderator
Nat Commun
. 2021 Dec 10;12(1):7222.
doi: 10.1038/s41467-021-27544-6.
Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction
Caroline Diorio[SUP] 1 2 [/SUP], Rawan Shraim[SUP] 1 3 [/SUP], Laura A Vella[SUP] 4 5 [/SUP], Josephine R Giles[SUP] 5 6 [/SUP], Amy E Baxter[SUP] 5 6 [/SUP], Derek A Oldridge[SUP] 5 6 7 [/SUP], Scott W Canna[SUP] 2 8 [/SUP], Sarah E Henrickson[SUP] 9 [/SUP], Kevin O McNerney[SUP] 1 [/SUP], Frances Balamuth[SUP] 10 [/SUP], Chakkapong Burudpakdee[SUP] 1 2 [/SUP], Jessica Lee[SUP] 1 2 [/SUP], Tomas Leng[SUP] 1 [/SUP], Alvin Farrel[SUP] 1 3 [/SUP], Michele P Lambert[SUP] 2 11 [/SUP], Kathleen E Sullivan[SUP] 2 9 [/SUP], E John Wherry[SUP] 5 6 [/SUP], David T Teachey[SUP] #[/SUP][SUP] 12 13 [/SUP], Hamid Bassiri[SUP] #[/SUP][SUP] 2 4 [/SUP], Edward M Behrens[SUP] #[/SUP][SUP] 2 8 [/SUP]
Affiliations
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.
. 2021 Dec 10;12(1):7222.
doi: 10.1038/s41467-021-27544-6.
Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction
Caroline Diorio[SUP] 1 2 [/SUP], Rawan Shraim[SUP] 1 3 [/SUP], Laura A Vella[SUP] 4 5 [/SUP], Josephine R Giles[SUP] 5 6 [/SUP], Amy E Baxter[SUP] 5 6 [/SUP], Derek A Oldridge[SUP] 5 6 7 [/SUP], Scott W Canna[SUP] 2 8 [/SUP], Sarah E Henrickson[SUP] 9 [/SUP], Kevin O McNerney[SUP] 1 [/SUP], Frances Balamuth[SUP] 10 [/SUP], Chakkapong Burudpakdee[SUP] 1 2 [/SUP], Jessica Lee[SUP] 1 2 [/SUP], Tomas Leng[SUP] 1 [/SUP], Alvin Farrel[SUP] 1 3 [/SUP], Michele P Lambert[SUP] 2 11 [/SUP], Kathleen E Sullivan[SUP] 2 9 [/SUP], E John Wherry[SUP] 5 6 [/SUP], David T Teachey[SUP] #[/SUP][SUP] 12 13 [/SUP], Hamid Bassiri[SUP] #[/SUP][SUP] 2 4 [/SUP], Edward M Behrens[SUP] #[/SUP][SUP] 2 8 [/SUP]
Affiliations
- PMID: 34893640
- DOI: 10.1038/s41467-021-27544-6
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.