دورية أكاديمية
أعرض في EDS

Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children.

التفاصيل البيبلوغرافية
العنوان: Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children.
المؤلفون: Boribong BP; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA., LaSalle TJ; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Program in Health Sciences and Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, USA., Bartsch YC; Harvard Medical School, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Ellett F; Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School, Boston, MA 02114, USA., Loiselle ME; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA., Davis JP; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA., Gonye ALK; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Sykes DB; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA., Hajizadeh S; Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Kreuzer J; Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA., Pillai S; Harvard Medical School, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Haas W; Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA., Edlow AG; Harvard Medical School, Boston, MA 02115, USA; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Boston, MA 02114, USA; Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA., Fasano A; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA., Alter G; Harvard Medical School, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Irimia D; Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School, Boston, MA 02114, USA., Sade-Feldman M; Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: msade-feldman@mgh.harvard.edu., Yonker LM; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: lyonker@mgh.harvard.edu.
المصدر: Cell reports. Medicine [Cell Rep Med] 2022 Dec 20; Vol. 3 (12), pp. 100848. Date of Electronic Publication: 2022 Nov 21.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2020]-
مواضيع طبية MeSH: Neutrophils* , COVID-19*, Humans ; Child ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/diagnosis
مستخلص: Multisystem inflammatory syndrome in children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory illness characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigenemia, cytokine storm, and immune dysregulation. In severe COVID-19, neutrophil activation is central to hyperinflammatory complications, yet the role of neutrophils in MIS-C is undefined. Here, we collect blood from 152 children: 31 cases of MIS-C, 43 cases of acute pediatric COVID-19, and 78 pediatric controls. We find that MIS-C neutrophils display a granulocytic myeloid-derived suppressor cell (G-MDSC) signature with highly altered metabolism that is distinct from the neutrophil interferon-stimulated gene (ISG) response we observe in pediatric COVID-19. Moreover, we observe extensive spontaneous neutrophil extracellular trap (NET) formation in MIS-C, and we identify neutrophil activation and degranulation signatures. Mechanistically, we determine that SARS-CoV-2 immune complexes are sufficient to trigger NETosis. Our findings suggest that hyperinflammatory presentation during MIS-C could be mechanistically linked to persistent SARS-CoV-2 antigenemia, driven by uncontrolled neutrophil activation and NET release in the vasculature.
Competing Interests: Declaration of interests M.S.-F. receives funding from Bristol-Myers Squibb. G.A. is a founder of Seromyx Systems, Inc. A.F. is co-founder of and stockholder in Alba Therapeutics.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
التعليقات: Update of: bioRxiv. 2021 Dec 20;:. (PMID: 34981052)
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معلومات مُعتمدة: K08 HL143183 United States HL NHLBI NIH HHS; T32 GM007753 United States GM NIGMS NIH HHS; T32 GM144273 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: COVID-19; RNA sequencing; multisystem inflammatory syndrome in children; neutrophil; neutrophil extracellular traps; pediatrics
SCR Disease Name: pediatric multisystem inflammatory disease, COVID-19 related
تواريخ الأحداث: Date Created: 20221208 Date Completed: 20221223 Latest Revision: 20240211
رمز التحديث: 20240211
مُعرف محوري في PubMed: PMC9676175
DOI: 10.1016/j.xcrm.2022.100848
PMID: 36476388
قاعدة البيانات: MEDLINE
الوصف
تدمد:2666-3791
DOI:10.1016/j.xcrm.2022.100848