Abstract
BACKGROUNDMultisystem inflammatory syndrome in children (MIS-C) is a rare but potentially severe illness that follows exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Kawasaki disease (KD) shares several clinical features with MIS-C, which prompted the use of intravenous immunoglobulin (IVIG), a mainstay therapy for KD. Both diseases share a robust activation of the innate immune system, including the IL-1 signaling pathway, and IL-1 blockade has been used for the treatment of both MIS-C and KD. The mechanism of action of IVIG in these 2 diseases and the cellular source of IL-1β have not been defined.METHODSThe effects of IVIG on peripheral blood leukocyte populations from patients with MIS-C and KD were examined using flow cytometry and mass cytometry (CyTOF) and live-cell imaging.RESULTSCirculating neutrophils were highly activated in patients with KD and MIS-C and were a major source of IL-1β. Following IVIG treatment, activated IL-1β+ neutrophils were reduced in the circulation. In vitro, IVIG was a potent activator of neutrophil cell death via PI3K and NADPH oxidase, but independently of caspase activation.CONCLUSIONSActivated neutrophils expressing IL-1β can be targeted by IVIG, supporting its use in both KD and MIS-C to ameliorate inflammation.FUNDINGPatient Centered Outcomes Research Institute; NIH; American Asthma Foundation; American Heart Association; Novo Nordisk Foundation; NIGMS; American Academy of Allergy, Asthma and Immunology Foundation.
Keywords: Apoptosis; COVID-19; Innate immunity; Neutrophils.
【저자키워드】 COVID-19, Neutrophils, Apoptosis, Innate immunity, 【초록키워드】 Treatment, SARS-CoV-2, Intravenous immunoglobulin, coronavirus, therapy, children, neutrophil, flow cytometry, MIS-C, Peripheral blood, innate immune system, heart, Kawasaki disease, Patient, signaling pathway, circulation, cell death, mechanism of action, disease, clinical feature, IL-1, caspase, IL-1β, cellular, NADPH oxidase, Inflammatory, Innate, Cytometry, acute respiratory syndrome, Activation, syndrome, foundation, blockade, PI3K, Effect, Academy, robust, examined, reduced, activated, expressing, leukocyte population, 【제목키워드】 Intravenous immunoglobulin, MIS-C, Kawasaki disease, Patient,