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Published on: March 24, 2017
Proteomic Profiling of MIS-C Patients Reveals Heterogeneity Relating to Interferon Gamma Dysregulation and Vascular
Insights
Multi-system Inflammatory Syndrome in Children (MIS-C) is a severe complication of COVID-19. Proteomic analysis revealed PLA2G2A as a key marker linked to thrombotic microangiopathy and identified dysregulated IFNγ responses.
Area of Science:
- Pediatric immunology
- Infectious disease pathology
- Proteomics and systems biology
Background:
- Multi-system Inflammatory Syndrome in Children (MIS-C) is a serious condition following SARS-CoV-2 infection.
- MIS-C presents with significant inflammation and cardiovascular issues in pediatric patients.
- Understanding MIS-C's heterogeneity is crucial for effective treatment.
Approach:
- Conducted a large-scale plasma proteome analysis of over 1400 proteins in children with SARS-CoV-2.
- Investigated protein signatures to understand hyperinflammation and vascular injury.
- Compared MIS-C proteomic data with other inflammatory syndromes like MAS and TMA.
Key Points:
- Protein signatures in MIS-C overlap with macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA).
- PLA2G2A was identified as a significant biomarker for MIS-C, correlating with TMA.
- Dysregulated Interferon-gamma (IFNγ) responses were observed in MIS-C patients.
Conclusions:
- IFNγ levels can differentiate clinical heterogeneity within MIS-C.
- Proteomic profiling offers insights into MIS-C pathogenesis and potential therapeutic targets.
- PLA2G2A serves as a potential diagnostic and prognostic marker for MIS-C associated with TMA.
Abstract:
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 IFNγ responses are dysregulated in MIS-C patients, and that IFNγ levels delineate clinical heterogeneity.
