Journal Article

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

Henrickson, Sarah E., Behrens, Edward M., Giles, Josephine R., Burudpakdee, Chakkapong, Lambert, Michele P., Teachey, David T., Diorio, Caroline, Lee, Jessica, McNerney, Kevin O., Wherry, E. John, Baxter, Amy E., Canna, Scott W., Vella, Laura A., Sullivan, Kathleen E., Farrel, Alvin, Bassiri, Hamid, Oldridge, Derek A., Shraim, Rawan, Leng, Tomas, Balamuth, Frances

2021

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/21 / 631/250/127/1212 / 631/250/255/2514 / 631/250/98 / 692/4023 / 692/53/2423 / 82/47 / Biomarkers / Case-Control Studies / Cell activation / Chemokine CXCL9 / Child / Children / Coronaviruses / COVID-19 / COVID-19 - complications / COVID-19 - metabolism / COVID-19 - pathology / Disorders / Endothelium, Vascular - physiopathology / Group II Phospholipases A2 / Heterogeneity / Humanities and Social Sciences / Humans / Infections / Inflammation / Interferon / Interferon-gamma - immunology / Interleukin-10 / Macrophages / multidisciplinary / Patients / Pediatrics / Phenotypes / Proteins / Proteome / Proteomes / Proteomics / Respiratory diseases / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Signs and symptoms / Systemic Inflammatory Response Syndrome - metabolism / Systemic Inflammatory Response Syndrome - pathology / Thrombotic microangiopathy / Vascular Diseases / Viral diseases / γ-Interferon