A Complement Atlas identifies interleukin 6 dependent alternative pathway dysregulation as a key druggable feature of COVID-19
- Author
- Karel Van Damme (UGent) , Levi Hoste (UGent) , Jozefien Declercq (UGent) , Elisabeth De Leeuw (UGent) , Bastiaan Maes, Liesbet Martens (UGent) , Roos Colman (UGent) , Robin Browaeys (UGent) , Cedric Bosteels (UGent) , Stijn Verwaerde (UGent) , Nicky Vermeulen, Sahine Lameire (UGent) , Nincy Debeuf (UGent) , Julie Deckers (UGent) , Patrick Stordeur, Martin Guilliams (UGent) , Sjoerd Schetters (UGent) , Filomeen Haerynck (UGent) , Simon Tavernier (UGent) and Bart Lambrecht (UGent)
- Organization
- Abstract
- To improve COVID-19 therapy, it is essential to understand the mechanisms driving critical illness. The complement system is an essential part of innate host defense that can also contribute to injury. All complement pathways have been implicated in COVID-19 pathogenesis, however the upstream drivers and downstream consequences on tissue injury remain ill-defined. Here, we demonstrate that complement activation is mediated by the alternative pathway and we provide a comprehensive atlas of the alterations in complement around the time of respiratory deterioration. Proteome and single-cell sequencing mapping across cell types and tissues reveals a division of labor between lung epithelial, stromal and myeloid cells in the production of complement, in addition to liver-derived factors. Upstream, IL-6 drives complement responses, linking complement dysregulation to approved COVID-19 therapies. In an exploratory proteomic study, C5 inhibition improves epithelial damage and markers of disease severity. Collectively, these results identify complement dysregulation as a key druggable feature of COVID-19.
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01GWSEW8W64S84X0Z8V3XFEDQG
- MLA
- Van Damme, Karel, et al. “A Complement Atlas Identifies Interleukin 6 Dependent Alternative Pathway Dysregulation as a Key Druggable Feature of COVID-19.” MedRxiv, Cold Spring Harbor Laboratory, 2023, doi:10.1101/2023.03.25.23287712.
- APA
- Van Damme, K., Hoste, L., Declercq, J., De Leeuw, E., Maes, B., Martens, L., … Lambrecht, B. (2023). A Complement Atlas identifies interleukin 6 dependent alternative pathway dysregulation as a key druggable feature of COVID-19. https://doi.org/10.1101/2023.03.25.23287712
- Chicago author-date
- Van Damme, Karel, Levi Hoste, Jozefien Declercq, Elisabeth De Leeuw, Bastiaan Maes, Liesbet Martens, Roos Colman, et al. 2023. “A Complement Atlas Identifies Interleukin 6 Dependent Alternative Pathway Dysregulation as a Key Druggable Feature of COVID-19.” MedRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2023.03.25.23287712.
- Chicago author-date (all authors)
- Van Damme, Karel, Levi Hoste, Jozefien Declercq, Elisabeth De Leeuw, Bastiaan Maes, Liesbet Martens, Roos Colman, Robin Browaeys, Cedric Bosteels, Stijn Verwaerde, Nicky Vermeulen, Sahine Lameire, Nincy Debeuf, Julie Deckers, Patrick Stordeur, Martin Guilliams, Sjoerd Schetters, Filomeen Haerynck, Simon Tavernier, and Bart Lambrecht. 2023. “A Complement Atlas Identifies Interleukin 6 Dependent Alternative Pathway Dysregulation as a Key Druggable Feature of COVID-19.” MedRxiv. Cold Spring Harbor Laboratory. doi:10.1101/2023.03.25.23287712.
- Vancouver
- 1.Van Damme K, Hoste L, Declercq J, De Leeuw E, Maes B, Martens L, et al. A Complement Atlas identifies interleukin 6 dependent alternative pathway dysregulation as a key druggable feature of COVID-19. medRxiv. Cold Spring Harbor Laboratory; 2023.
- IEEE
- [1]K. Van Damme et al., “A Complement Atlas identifies interleukin 6 dependent alternative pathway dysregulation as a key druggable feature of COVID-19,” medRxiv. Cold Spring Harbor Laboratory, 2023.
@misc{01GWSEW8W64S84X0Z8V3XFEDQG,
abstract = {{To improve COVID-19 therapy, it is essential to understand the mechanisms driving critical illness. The complement system is an essential part of innate host defense that can also contribute to injury. All complement pathways have been implicated in COVID-19 pathogenesis, however the upstream drivers and downstream consequences on tissue injury remain ill-defined. Here, we demonstrate that complement activation is mediated by the alternative pathway and we provide a comprehensive atlas of the alterations in complement around the time of respiratory deterioration. Proteome and single-cell sequencing mapping across cell types and tissues reveals a division of labor between lung epithelial, stromal and myeloid cells in the production of complement, in addition to liver-derived factors. Upstream, IL-6 drives complement responses, linking complement dysregulation to approved COVID-19 therapies. In an exploratory proteomic study, C5 inhibition improves epithelial damage and markers of disease severity. Collectively, these results identify complement dysregulation as a key druggable feature of COVID-19.}},
author = {{Van Damme, Karel and Hoste, Levi and Declercq, Jozefien and De Leeuw, Elisabeth and Maes, Bastiaan and Martens, Liesbet and Colman, Roos and Browaeys, Robin and Bosteels, Cedric and Verwaerde, Stijn and Vermeulen, Nicky and Lameire, Sahine and Debeuf, Nincy and Deckers, Julie and Stordeur, Patrick and Guilliams, Martin and Schetters, Sjoerd and Haerynck, Filomeen and Tavernier, Simon and Lambrecht, Bart}},
language = {{eng}},
publisher = {{Cold Spring Harbor Laboratory}},
series = {{medRxiv}},
title = {{A Complement Atlas identifies interleukin 6 dependent alternative pathway dysregulation as a key druggable feature of COVID-19}},
url = {{http://doi.org/10.1101/2023.03.25.23287712}},
year = {{2023}},
}
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