{"doi":"10.1172/jci147076","title":"Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C","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.","journal":"Journal of Clinical Investigation","year":2021,"id":153095,"datarank":0.6414999178524083,"base_score":4.276666119016055,"endowment":4.276666119016055,"self_citation_contribution":0.6414999178524083,"citation_network_contribution":0.0,"self_endowment_contribution":0.6414999178524083,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":71,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9649,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":563281,"name":"Isaac Shamie","orcid":"0000-0002-6122-2905","position":1,"is_corresponding":false},{"id":649682,"name":"Jamie Casey Lee","orcid":"0000-0001-5465-3670","position":2,"is_corresponding":false},{"id":338853,"name":"Cameron J. 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