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.

• Authors: Yanfang P Zhu, Isaac Shamie, Jamie C Lee, Cameron J Nowell, Weiqi Peng, Shiela Angulo, Linh Nn Le, Yushan Liu, Huilai Miao, Hainan Xiong, Cathleen J Pena, Elizabeth Moreno, Eric Griffis, Stephanie G Labou, Alessandra Franco, Lori Broderick, Hal M Hoffman, Chisato Shimizu, Nathan E Lewis, John T Kanegaye, Adriana H Tremoulet, Jane C Burns, Ben A Croker, Pediatric Emergency Medicine Kawasaki Disease Research Group Consortium
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 131 Issue 20 (10 15 2021) ISSN: 1558-8238 [Electronic] United States
• PMID: 34464357 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• FASLG protein, human
• Fas Ligand Protein
• IL1B protein, human
• Immunoglobulins, Intravenous
• Interleukin-1beta

Topics

• COVID-19 (blood, complications, immunology, therapy)
• Case-Control Studies
• Cell Death (immunology)
• Cell Lineage (immunology)
• Child
• Child, Preschool
• Fas Ligand Protein (immunology)
• Female
• Humans
• Immunoglobulins, Intravenous (therapeutic use)
• Infant
• Interleukin-1beta (antagonists & inhibitors, blood)
• Leukocyte Count
• Male
• Mucocutaneous Lymph Node Syndrome (blood, immunology, therapy)
• Neutrophil Activation
• Neutrophils (classification, immunology, pathology)
• Systemic Inflammatory Response Syndrome (blood, immunology, therapy)