Related Experiment Video
Updated: Oct 10, 2025
High-Throughput Transcriptome Analysis for Investigating Host-Pathogen Interactions
Published on: March 5, 2022
Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular
Caroline Diorio1,2, Rawan Shraim1,3, Laura A Vella4,5
1Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Insights
Multi-system Inflammatory Syndrome in Children (MIS-C) is a severe complication of COVID-19. This study analyzed over 1400 proteins in children, revealing key inflammatory markers and potential therapeutic targets for MIS-C.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Proteomics
Background:
- Multi-system Inflammatory Syndrome in Children (MIS-C) is a serious complication following SARS-CoV-2 infection.
- MIS-C presents with significant cardiovascular and hyperinflammatory symptoms in pediatric patients.
- Initial SARS-CoV-2 infection is often mild or asymptomatic before MIS-C onset.
Purpose of the Study:
- To comprehensively analyze the plasma proteome in children with SARS-CoV-2 infection.
- To identify protein signatures reflecting hyperinflammation and vascular injury in MIS-C.
- To discover pathogenic mediators and potential biomarkers for MIS-C.
Main Methods:
- Plasma proteomic analysis of over 1400 proteins.
- Comparative analysis of protein signatures in MIS-C, macrophage activation syndrome (MAS), and thrombotic microangiopathy (TMA).
- Assessment of interferon-gamma (IFNγ) levels and their correlation with clinical heterogeneity.
Main Results:
- Protein signatures show overlap between MIS-C, MAS, and TMA.
- PLA2G2A identified as a significant MIS-C marker associated with TMA.
- Dysregulated IFNγ responses observed in MIS-C patients, correlating with clinical variations.
Conclusions:
- The plasma proteome provides insights into MIS-C pathogenesis, highlighting links to other inflammatory syndromes.
- PLA2G2A and IFNγ are potential biomarkers for MIS-C diagnosis and understanding disease heterogeneity.
- Further research into these mediators may guide targeted therapies for MIS-C.
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.
More Related Videos
08:09Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
Published on: March 24, 2017
10:37Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform
Published on: November 30, 2016