tetano
Editor, Senior Moderator
J Clin Invest
. 2021 Aug 31;147076.
doi: 10.1172/JCI147076. Online ahead of print.
Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C
Yanfang P Zhu[SUP] 1 [/SUP], Isaac Shamie[SUP] 1 [/SUP], Jamie Casey Lee[SUP] 2 [/SUP], Cameron J Nowell[SUP] 3 [/SUP], Weiqi Peng[SUP] 2 [/SUP], Shiela Angulo[SUP] 2 [/SUP], Linh Nn Le[SUP] 2 [/SUP], Yushan Liu[SUP] 2 [/SUP], Huilai Miao[SUP] 2 [/SUP], Hainan Xiong[SUP] 2 [/SUP], Cathleen J Pena[SUP] 2 [/SUP], Elizabeth Moreno[SUP] 2 [/SUP], Eric Griffis[SUP] 4 [/SUP], Stephanie G Labou[SUP] 5 [/SUP], Alessandra Franco[SUP] 1 [/SUP], Lori Broderick[SUP] 2 [/SUP], Hal M Hoffman[SUP] 2 [/SUP], Chisato Shimizu[SUP] 2 [/SUP], Nathan E Lewis[SUP] 2 [/SUP], John T Kanegaye[SUP] 2 [/SUP], Adriana H Tremoulet[SUP] 2 [/SUP], Jane C Burns[SUP] 2 [/SUP], Ben A Croker[SUP] 2 [/SUP]
Affiliations
Abstract
Background: Multisystem inflammatory syndrome in children (MIS-C) is a rare but potentially severe illness that follows exposure to severe acute respiratory syndrome-related 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 two diseases and the cellular source of IL-1b have not been defined.
Methods: The effects of IVIG on peripheral blood leukocyte populations from patients with MIS-C and KD were examined using flow cytometry, mass cytometry (CyTOF), and live cell imaging.
Results: Circulating 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 PI3-K and NADPH oxidase but independently of caspase activation.
Conclusions: Activated neutrophils expressing IL-1β can be targeted by IVIG, supporting its use in both KD and MIS-C to ameliorate inflammation.
Keywords: Apoptosis; COVID-19; Innate immunity; Neutrophils.
. 2021 Aug 31;147076.
doi: 10.1172/JCI147076. Online ahead of print.
Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C
Yanfang P Zhu[SUP] 1 [/SUP], Isaac Shamie[SUP] 1 [/SUP], Jamie Casey Lee[SUP] 2 [/SUP], Cameron J Nowell[SUP] 3 [/SUP], Weiqi Peng[SUP] 2 [/SUP], Shiela Angulo[SUP] 2 [/SUP], Linh Nn Le[SUP] 2 [/SUP], Yushan Liu[SUP] 2 [/SUP], Huilai Miao[SUP] 2 [/SUP], Hainan Xiong[SUP] 2 [/SUP], Cathleen J Pena[SUP] 2 [/SUP], Elizabeth Moreno[SUP] 2 [/SUP], Eric Griffis[SUP] 4 [/SUP], Stephanie G Labou[SUP] 5 [/SUP], Alessandra Franco[SUP] 1 [/SUP], Lori Broderick[SUP] 2 [/SUP], Hal M Hoffman[SUP] 2 [/SUP], Chisato Shimizu[SUP] 2 [/SUP], Nathan E Lewis[SUP] 2 [/SUP], John T Kanegaye[SUP] 2 [/SUP], Adriana H Tremoulet[SUP] 2 [/SUP], Jane C Burns[SUP] 2 [/SUP], Ben A Croker[SUP] 2 [/SUP]
Affiliations
- PMID: 34464357
- DOI: 10.1172/JCI147076
Abstract
Background: Multisystem inflammatory syndrome in children (MIS-C) is a rare but potentially severe illness that follows exposure to severe acute respiratory syndrome-related 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 two diseases and the cellular source of IL-1b have not been defined.
Methods: The effects of IVIG on peripheral blood leukocyte populations from patients with MIS-C and KD were examined using flow cytometry, mass cytometry (CyTOF), and live cell imaging.
Results: Circulating 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 PI3-K and NADPH oxidase but independently of caspase activation.
Conclusions: Activated neutrophils expressing IL-1β can be targeted by IVIG, supporting its use in both KD and MIS-C to ameliorate inflammation.
Keywords: Apoptosis; COVID-19; Innate immunity; Neutrophils.