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Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons

The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. While regulatory T (Treg) and B (Breg) cells, as the main elements of immune homeostasis, contribute to the control of hyperinflammation during COVID-19 infection, we...

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Autores principales: Saheb Sharif-Askari, Fatemeh, Saheb Sharif-Askari, Narjes, Hafezi, Shirin, Alsayed, Hawra Ali Hussain, Selvakumar, Balachandar, Eladham, Mariam Wed Abdelaziz, Mdkhana, Bushra, Bayram, Ola Salam, Temsah, Mohamad-Hani, Halwani, Rabih
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10575900/
https://www.ncbi.nlm.nih.gov/pubmed/37833265
http://dx.doi.org/10.1038/s41598-023-43675-w
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author Saheb Sharif-Askari, Fatemeh
Saheb Sharif-Askari, Narjes
Hafezi, Shirin
Alsayed, Hawra Ali Hussain
Selvakumar, Balachandar
Eladham, Mariam Wed Abdelaziz
Mdkhana, Bushra
Bayram, Ola Salam
Temsah, Mohamad-Hani
Halwani, Rabih
author_facet Saheb Sharif-Askari, Fatemeh
Saheb Sharif-Askari, Narjes
Hafezi, Shirin
Alsayed, Hawra Ali Hussain
Selvakumar, Balachandar
Eladham, Mariam Wed Abdelaziz
Mdkhana, Bushra
Bayram, Ola Salam
Temsah, Mohamad-Hani
Halwani, Rabih
author_sort Saheb Sharif-Askari, Fatemeh
collection PubMed
description The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. While regulatory T (Treg) and B (Breg) cells, as the main elements of immune homeostasis, contribute to the control of hyperinflammation during COVID-19 infection, we hypothesized change in their levels in relation to disease severity and the presence of autoantibodies (auto-Abs) to type I IFNs. Cytometric analysis of blood of 62 COVID-19 patients with different severities revealed an increased proportion of conventional (cTreg; CD25(+)FoxP3(+)) and unconventional (uTreg; CD25(-)FoxP3(+)) Tregs, as well as the LAG3(+) immune suppressive form of cTreg/uTreg, in the blood of severe COVID-19 cases compared to the milder, non-hospitalized cases. The increase in blood levels of cTreg/uTreg, but not LAG3(+) cTreg/uTreg subtypes, was even higher among patients with severe COVID-19 and auto-Abs to type I IFNs. Regarding Bregs, compared to the milder, non-hospitalized cases, the proportion of IL-35(+) and IL-10(+) Bregs was elevated in the blood of severe COVID-19 patients, and to a higher extent in those with auto-Abs to type I IFNs. Moreover, blood levels of cTreg, LAG3(+) cTreg/uTreg, and IL-35(+) and IL-10(+) Breg subtypes were associated with lower blood levels of proinflammatory cytokines such as IL-6, IL-17, TNFα, and IL-1β. Interestingly, patients who were treated with either tocilizumab and/or a high dose of Vitamin D had higher blood levels of these regulatory cells and better control of the proinflammatory cytokines. These observations suggest that perturbations in the levels of immunomodulatory Tregs and Bregs occur in COVID-19, especially in the presence of auto-Abs to type I IFNs.
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spelling pubmed-105759002023-10-15 Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons Saheb Sharif-Askari, Fatemeh Saheb Sharif-Askari, Narjes Hafezi, Shirin Alsayed, Hawra Ali Hussain Selvakumar, Balachandar Eladham, Mariam Wed Abdelaziz Mdkhana, Bushra Bayram, Ola Salam Temsah, Mohamad-Hani Halwani, Rabih Sci Rep Article The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. While regulatory T (Treg) and B (Breg) cells, as the main elements of immune homeostasis, contribute to the control of hyperinflammation during COVID-19 infection, we hypothesized change in their levels in relation to disease severity and the presence of autoantibodies (auto-Abs) to type I IFNs. Cytometric analysis of blood of 62 COVID-19 patients with different severities revealed an increased proportion of conventional (cTreg; CD25(+)FoxP3(+)) and unconventional (uTreg; CD25(-)FoxP3(+)) Tregs, as well as the LAG3(+) immune suppressive form of cTreg/uTreg, in the blood of severe COVID-19 cases compared to the milder, non-hospitalized cases. The increase in blood levels of cTreg/uTreg, but not LAG3(+) cTreg/uTreg subtypes, was even higher among patients with severe COVID-19 and auto-Abs to type I IFNs. Regarding Bregs, compared to the milder, non-hospitalized cases, the proportion of IL-35(+) and IL-10(+) Bregs was elevated in the blood of severe COVID-19 patients, and to a higher extent in those with auto-Abs to type I IFNs. Moreover, blood levels of cTreg, LAG3(+) cTreg/uTreg, and IL-35(+) and IL-10(+) Breg subtypes were associated with lower blood levels of proinflammatory cytokines such as IL-6, IL-17, TNFα, and IL-1β. Interestingly, patients who were treated with either tocilizumab and/or a high dose of Vitamin D had higher blood levels of these regulatory cells and better control of the proinflammatory cytokines. These observations suggest that perturbations in the levels of immunomodulatory Tregs and Bregs occur in COVID-19, especially in the presence of auto-Abs to type I IFNs. Nature Publishing Group UK 2023-10-13 /pmc/articles/PMC10575900/ /pubmed/37833265 http://dx.doi.org/10.1038/s41598-023-43675-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Saheb Sharif-Askari, Fatemeh
Saheb Sharif-Askari, Narjes
Hafezi, Shirin
Alsayed, Hawra Ali Hussain
Selvakumar, Balachandar
Eladham, Mariam Wed Abdelaziz
Mdkhana, Bushra
Bayram, Ola Salam
Temsah, Mohamad-Hani
Halwani, Rabih
Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons
title Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons
title_full Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons
title_fullStr Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons
title_full_unstemmed Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons
title_short Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons
title_sort increased blood immune regulatory cells in severe covid-19 with autoantibodies to type i interferons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10575900/
https://www.ncbi.nlm.nih.gov/pubmed/37833265
http://dx.doi.org/10.1038/s41598-023-43675-w
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