4.7 Article

Evidence, detailed characterization and clinical context of complement activation in acute multisystem inflammatory syndrome in children

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SCIENTIFIC REPORTS
卷 12, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-022-23806-5

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  1. Semmelweis University
  2. European Union-Next Generation EU [TKP2021-EGA-24]
  3. Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund [TKP2021-EGA]
  4. Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary
  5. National Office for Innovation and Research [2020-1.1.6JOVO-2021-00013, 860044]

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Multisystem inflammatory syndrome in children (MIS-C) is a rare and life-threatening complication of SARS-CoV-2 infection. This syndrome is characterized by high fever, inflammation, and shock-like symptoms. Activation of immune cells and inflammation markers play a crucial role in the pathogenesis, and treatment with intravenous immunoglobulin leads to improvement of the disease. Complement system activation is closely related to the disease activity and its reduction is associated with rapid improvement after treatment.
Multisystem inflammatory syndrome in children (MIS-C) is a rare, life-threatening complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MIS-C develops with high fever, marked inflammation and shock-like picture several weeks after exposure to, or mild infection with SARS-CoV-2. Deep immune profiling identified activated macrophages, neutrophils, B-plasmablasts and CD8 + T cells as key determinants of pathogenesis together with multiple inflammatory markers. The disease rapidly responds to intravenous immunoglobulin (IVIG) treatment with clear changes of immune features. Here we present the results of a comprehensive analysis of the complement system in the context of MIS-C activity and describe characteristic changes during IVIG treatment. We show that activation markers of the classical, alternative and terminal pathways are highly elevated, that the activation is largely independent of anti-SARS-CoV-2 humoral immune response, but is strongly associated with markers of macrophage activation. Decrease of complement activation is closely associated with rapid improvement of MIS-C after IVIG treatment.

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