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SARS-CoV-2 Antibodies Mediate Complement and Cellular Driven Inflammation

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to constitute a serious public health threat worldwide. Protective antibody-mediated viral neutralization in response to SARS-CoV-2 infection has been firm...

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Autores principales: Jarlhelt, Ida, Nielsen, Sif Kaas, Jahn, Camilla Xenia Holtermann, Hansen, Cecilie Bo, Pérez-Alós, Laura, Rosbjerg, Anne, Bayarri-Olmos, Rafael, Skjoedt, Mikkel-Ole, Garred, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596567/
https://www.ncbi.nlm.nih.gov/pubmed/34804055
http://dx.doi.org/10.3389/fimmu.2021.767981
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author Jarlhelt, Ida
Nielsen, Sif Kaas
Jahn, Camilla Xenia Holtermann
Hansen, Cecilie Bo
Pérez-Alós, Laura
Rosbjerg, Anne
Bayarri-Olmos, Rafael
Skjoedt, Mikkel-Ole
Garred, Peter
author_facet Jarlhelt, Ida
Nielsen, Sif Kaas
Jahn, Camilla Xenia Holtermann
Hansen, Cecilie Bo
Pérez-Alós, Laura
Rosbjerg, Anne
Bayarri-Olmos, Rafael
Skjoedt, Mikkel-Ole
Garred, Peter
author_sort Jarlhelt, Ida
collection PubMed
description The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to constitute a serious public health threat worldwide. Protective antibody-mediated viral neutralization in response to SARS-CoV-2 infection has been firmly characterized. Where the effects of the antibody response are generally considered to be beneficial, an important biological question regarding potential negative outcomes of a SARS-CoV-2 antibody response has yet to be answered. We determined the distribution of IgG subclasses and complement activation levels in plasma from convalescent individuals using in-house developed ELISAs. The IgG response towards SARS-CoV-2 receptor-binding domain (RBD) after natural infection appeared to be mainly driven by IgG1 and IgG3 subclasses, which are the main ligands for C1q mediated classical complement pathway activation. The deposition of the complement components C4b, C3bc, and TCC as a consequence of SARS-CoV-2 specific antibodies were depending primarily on the SARS-CoV-2 RBD and significantly correlated with both IgG levels and disease severity, indicating that individuals with high levels of IgG and/or severe disease, might have a more prominent complement activation during viral infection. Finally, freshly isolated monocytes and a monocyte cell line (THP-1) were used to address the cellular mediated inflammatory response as a consequence of Fc-gamma receptor engagement by SARS-CoV-2 specific antibodies. Monocytic Fc gamma receptor charging resulted in a significant rise in the secretion of the pro-inflammatory cytokine TNF-α. Our results indicate that SARS-CoV-2 antibodies might drive significant inflammatory responses through the classical complement pathway and via cellular immune-complex activation that could have negative consequences during COVID-19 disease. We found that increased classical complement activation was highly associated to COVID-19 disease severity. The combination of antibody-mediated complement activation and subsequent cellular priming could constitute a significant risk of exacerbating COVID-19 severity.
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spelling pubmed-85965672021-11-18 SARS-CoV-2 Antibodies Mediate Complement and Cellular Driven Inflammation Jarlhelt, Ida Nielsen, Sif Kaas Jahn, Camilla Xenia Holtermann Hansen, Cecilie Bo Pérez-Alós, Laura Rosbjerg, Anne Bayarri-Olmos, Rafael Skjoedt, Mikkel-Ole Garred, Peter Front Immunol Immunology The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to constitute a serious public health threat worldwide. Protective antibody-mediated viral neutralization in response to SARS-CoV-2 infection has been firmly characterized. Where the effects of the antibody response are generally considered to be beneficial, an important biological question regarding potential negative outcomes of a SARS-CoV-2 antibody response has yet to be answered. We determined the distribution of IgG subclasses and complement activation levels in plasma from convalescent individuals using in-house developed ELISAs. The IgG response towards SARS-CoV-2 receptor-binding domain (RBD) after natural infection appeared to be mainly driven by IgG1 and IgG3 subclasses, which are the main ligands for C1q mediated classical complement pathway activation. The deposition of the complement components C4b, C3bc, and TCC as a consequence of SARS-CoV-2 specific antibodies were depending primarily on the SARS-CoV-2 RBD and significantly correlated with both IgG levels and disease severity, indicating that individuals with high levels of IgG and/or severe disease, might have a more prominent complement activation during viral infection. Finally, freshly isolated monocytes and a monocyte cell line (THP-1) were used to address the cellular mediated inflammatory response as a consequence of Fc-gamma receptor engagement by SARS-CoV-2 specific antibodies. Monocytic Fc gamma receptor charging resulted in a significant rise in the secretion of the pro-inflammatory cytokine TNF-α. Our results indicate that SARS-CoV-2 antibodies might drive significant inflammatory responses through the classical complement pathway and via cellular immune-complex activation that could have negative consequences during COVID-19 disease. We found that increased classical complement activation was highly associated to COVID-19 disease severity. The combination of antibody-mediated complement activation and subsequent cellular priming could constitute a significant risk of exacerbating COVID-19 severity. Frontiers Media S.A. 2021-11-02 /pmc/articles/PMC8596567/ /pubmed/34804055 http://dx.doi.org/10.3389/fimmu.2021.767981 Text en Copyright © 2021 Jarlhelt, Nielsen, Jahn, Hansen, Pérez-Alós, Rosbjerg, Bayarri-Olmos, Skjoedt and Garred 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
Jarlhelt, Ida
Nielsen, Sif Kaas
Jahn, Camilla Xenia Holtermann
Hansen, Cecilie Bo
Pérez-Alós, Laura
Rosbjerg, Anne
Bayarri-Olmos, Rafael
Skjoedt, Mikkel-Ole
Garred, Peter
SARS-CoV-2 Antibodies Mediate Complement and Cellular Driven Inflammation
title SARS-CoV-2 Antibodies Mediate Complement and Cellular Driven Inflammation
title_full SARS-CoV-2 Antibodies Mediate Complement and Cellular Driven Inflammation
title_fullStr SARS-CoV-2 Antibodies Mediate Complement and Cellular Driven Inflammation
title_full_unstemmed SARS-CoV-2 Antibodies Mediate Complement and Cellular Driven Inflammation
title_short SARS-CoV-2 Antibodies Mediate Complement and Cellular Driven Inflammation
title_sort sars-cov-2 antibodies mediate complement and cellular driven inflammation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596567/
https://www.ncbi.nlm.nih.gov/pubmed/34804055
http://dx.doi.org/10.3389/fimmu.2021.767981
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