Summary Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells, with increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL-6 may be preferable to IL-1 or TNF-α. We identified several potential mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C suggesting complement inhibitors could be used to treat the disease. Graphical abstract Highlights • Granulocyte frequency correlates with MIS-C disease severity at presentation • Recovering patients have increased CD163 on monocytes and new atypical neutrophils • Cytokine profile of acute MIS-C suggests inhibiting IL6 rather than IL1 or TNF • Raised plasma C5b-9 identifies complement inhibitors as potential MIS-C therapy Genomics; Immune response; Immune system disorder; Immunology
【저자키워드】 immunology, immune response, Genomics, Immune system disorder, 【초록키워드】 COVID-19, SARS-CoV-2, coronavirus, therapy, IL-6, children, disease severity, neutrophil, T-cells, Infection, IL6, complement, immune, MIS-C, memory, monocyte, immune profiling, therapeutic, Patient, plasma, Complement inhibitor, disease, patients, IL-1, TNF-α, B-cell, TNF, Activated neutrophils, Frequency, Inflammatory, Atypical, B-cells, post treatment, acute respiratory syndrome, Activation, Abstract, potential mechanism, syndrome, life-threatening, plasmablast, treat, symptom resolution, CD163, CD8+, feature, deep, identify, the disease, inhibiting, classical monocyte, immature neutrophil, 【제목키워드】 immune, MIS-C, disease,