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MIS-C: A COVID-19-as sociated condition between hypoimmunity and hyperimmunity
Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of COVID-19. A better knowledge of immunological, cellular, and genetic characteristics of MIS-C could help better understand the pathogenesis of the disease and contribute to identifying specific diagnostic biomark...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574022/ https://www.ncbi.nlm.nih.gov/pubmed/36263058 http://dx.doi.org/10.3389/fimmu.2022.985433 |
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author | Gelzo, Monica Castaldo, Alice Giannattasio, Antonietta Scalia, Giulia Raia, Maddalena Esposito, Maria Valeria Maglione, Marco Muzzica, Stefania D’Anna, Carolina Grieco, Michela Tipo, Vincenzo La Cava, Antonio Castaldo, Giuseppe |
author_facet | Gelzo, Monica Castaldo, Alice Giannattasio, Antonietta Scalia, Giulia Raia, Maddalena Esposito, Maria Valeria Maglione, Marco Muzzica, Stefania D’Anna, Carolina Grieco, Michela Tipo, Vincenzo La Cava, Antonio Castaldo, Giuseppe |
author_sort | Gelzo, Monica |
collection | PubMed |
description | Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of COVID-19. A better knowledge of immunological, cellular, and genetic characteristics of MIS-C could help better understand the pathogenesis of the disease and contribute to identifying specific diagnostic biomarkers and develop targeted therapies. We studied 37 MIS-C children at hospital admission and 24 healthy controls analyzing serum cytokines (IFN-α, IFN-β, IFN-γ, IL-6, IL-10, IL-17A, IL-12p70 and TNF), lymphocyte populations by flow cytometry and 386 genes related to autoimmune diseases, autoinflammation and primary immunodeficiencies by NGS. MIS-C patients showed a significant increase of serum IFNγ (despite a significant reduction of activated Th1) and ILs, even if with a great heterogeneity among patients, revealing different pathways involved in MIS-C pathogenesis and suggesting that serum cytokines at admission may help to select the inflammatory pathways to target in each patient. Flow cytometry demonstrated a relevant reduction of T populations while the percentage of B cell was increased in agreement with an autoimmune pathogenesis of MIS-C. Genetic analysis identified variants in 34 genes and 83.3% of patients had at least one gene variant. Among these, 9 were mutated in more patients. Most genes are related to autoimmune diseases like ATM, NCF1, MCM4, FCN3, and DOCK8 or to autoinflammatory diseases associated to the release of IFNγ like PRF1, NOD2, and MEF. Thus, an incomplete clearance of the Sars-CoV2 during the acute phase may induce tissue damage and self-antigen exposure and genetic variants can predispose to hyper-reactive immune dysregulation events of MIS-C-syndrome. Type II IFN activation and cytokine responses (mainly IL-6 and IL-10) may cause a cytokine storm in some patients with a more severe acute phase of the disease, lymphopenia and multisystemic organ involvement. The timely identification of such patients with an immunocytometric panel might be critical for targeted therapeutic management. |
format | Online Article Text |
id | pubmed-9574022 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95740222022-10-18 MIS-C: A COVID-19-as sociated condition between hypoimmunity and hyperimmunity Gelzo, Monica Castaldo, Alice Giannattasio, Antonietta Scalia, Giulia Raia, Maddalena Esposito, Maria Valeria Maglione, Marco Muzzica, Stefania D’Anna, Carolina Grieco, Michela Tipo, Vincenzo La Cava, Antonio Castaldo, Giuseppe Front Immunol Immunology Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of COVID-19. A better knowledge of immunological, cellular, and genetic characteristics of MIS-C could help better understand the pathogenesis of the disease and contribute to identifying specific diagnostic biomarkers and develop targeted therapies. We studied 37 MIS-C children at hospital admission and 24 healthy controls analyzing serum cytokines (IFN-α, IFN-β, IFN-γ, IL-6, IL-10, IL-17A, IL-12p70 and TNF), lymphocyte populations by flow cytometry and 386 genes related to autoimmune diseases, autoinflammation and primary immunodeficiencies by NGS. MIS-C patients showed a significant increase of serum IFNγ (despite a significant reduction of activated Th1) and ILs, even if with a great heterogeneity among patients, revealing different pathways involved in MIS-C pathogenesis and suggesting that serum cytokines at admission may help to select the inflammatory pathways to target in each patient. Flow cytometry demonstrated a relevant reduction of T populations while the percentage of B cell was increased in agreement with an autoimmune pathogenesis of MIS-C. Genetic analysis identified variants in 34 genes and 83.3% of patients had at least one gene variant. Among these, 9 were mutated in more patients. Most genes are related to autoimmune diseases like ATM, NCF1, MCM4, FCN3, and DOCK8 or to autoinflammatory diseases associated to the release of IFNγ like PRF1, NOD2, and MEF. Thus, an incomplete clearance of the Sars-CoV2 during the acute phase may induce tissue damage and self-antigen exposure and genetic variants can predispose to hyper-reactive immune dysregulation events of MIS-C-syndrome. Type II IFN activation and cytokine responses (mainly IL-6 and IL-10) may cause a cytokine storm in some patients with a more severe acute phase of the disease, lymphopenia and multisystemic organ involvement. The timely identification of such patients with an immunocytometric panel might be critical for targeted therapeutic management. Frontiers Media S.A. 2022-10-03 /pmc/articles/PMC9574022/ /pubmed/36263058 http://dx.doi.org/10.3389/fimmu.2022.985433 Text en Copyright © 2022 Gelzo, Castaldo, Giannattasio, Scalia, Raia, Esposito, Maglione, Muzzica, D’Anna, Grieco, Tipo, La Cava and Castaldo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Gelzo, Monica Castaldo, Alice Giannattasio, Antonietta Scalia, Giulia Raia, Maddalena Esposito, Maria Valeria Maglione, Marco Muzzica, Stefania D’Anna, Carolina Grieco, Michela Tipo, Vincenzo La Cava, Antonio Castaldo, Giuseppe MIS-C: A COVID-19-as sociated condition between hypoimmunity and hyperimmunity |
title | MIS-C: A COVID-19-as sociated condition between hypoimmunity and hyperimmunity |
title_full | MIS-C: A COVID-19-as sociated condition between hypoimmunity and hyperimmunity |
title_fullStr | MIS-C: A COVID-19-as sociated condition between hypoimmunity and hyperimmunity |
title_full_unstemmed | MIS-C: A COVID-19-as sociated condition between hypoimmunity and hyperimmunity |
title_short | MIS-C: A COVID-19-as sociated condition between hypoimmunity and hyperimmunity |
title_sort | mis-c: a covid-19-as sociated condition between hypoimmunity and hyperimmunity |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574022/ https://www.ncbi.nlm.nih.gov/pubmed/36263058 http://dx.doi.org/10.3389/fimmu.2022.985433 |
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