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.
【저자키워드】 viral infection, interferons, chemokines, Predictive markers, rheumatology, 【초록키워드】 severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, Inflammation, Macrophage, coronavirus, SARS-COV-2 infection, children, Infection, coronavirus 2, Symptoms, heterogeneity, MIS-C, Severe acute respiratory syndrome, Protein, Asymptomatic, response, hyperinflammation, Pediatric patients, phenotype, Mild, plasma, macrophage activation syndrome, proteome, respiratory, disease, patients, IFN-γ, marker, thrombotic microangiopathy, Inflammatory, mediators, Vascular injury, overlap, acute respiratory syndrome coronavirus, comprehensive analysis, IFNγ, syndrome, thrombotic, pathogenic, clinical heterogeneity, IFNγ levels, PLA2G2A, Hyperinflammatory, initial, identify, dysregulated, IFN-γ response, IFNγ level, infection with SARS-CoV-2, Week, 【제목키워드】 Endothelial dysfunction, Patient, interferon gamma, dysregulation, Vascular, indicate,