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  • Title: Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C.
    Author: Zhu YP, Shamie I, Lee JC, Nowell CJ, Peng W, Angulo S, Le LN, Liu Y, Miao H, Xiong H, Pena CJ, Moreno E, Griffis E, Labou SG, Franco A, Broderick L, Hoffman HM, Shimizu C, Lewis NE, Kanegaye JT, Tremoulet AH, Burns JC, Croker BA, Pediatric Emergency Medicine Kawasaki Disease Research Group Consortium.
    Journal: J Clin Invest; 2021 Oct 15; 131(20):. PubMed ID: 34464357.
    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.
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