Thromboinflammation Supports Complement Activation in Cancer Patients With COVID-19.
Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers
/ blood
COVID-19
/ blood
Complement Activation
/ immunology
Complement Inactivating Agents
/ blood
Female
Fibrin Fibrinogen Degradation Products
/ metabolism
Humans
Inflammation
/ blood
Male
Middle Aged
Neoplasms
/ blood
Platelet Activation
/ immunology
Retrospective Studies
SARS-CoV-2
/ immunology
Thrombosis
/ blood
Young Adult
COVID-19
cancer
complement
endothelial dysfunction
thromboinflammation
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
28
05
2021
accepted:
02
08
2021
entrez:
7
9
2021
pubmed:
8
9
2021
medline:
21
9
2021
Statut:
epublish
Résumé
COVID-19 pathology is associated with exuberant inflammation, vascular damage, and activation of coagulation. In addition, complement activation has been described and is linked to disease pathology. However, few studies have been conducted in cancer patients. This study examined complement activation in response to COVID-19 in the setting of cancer associated thromboinflammation. Markers of complement activation (C3a, C5a, sC5b-9) and complement inhibitors (Factor H, C1-Inhibitor) were evaluated in plasma of cancer patients with (n=43) and without (n=43) COVID-19 and stratified based on elevated plasma D-dimer levels (>1.0 μg/ml FEU). Markers of vascular endothelial cell dysfunction and platelet activation (ICAM-1, thrombomodulin, P-selectin) as well as systemic inflammation (pentraxin-3, serum amyloid A, soluble urokinase plasminogen activator receptor) were analyzed to further evaluate the inflammatory response. Increases in circulating markers of endothelial cell dysfunction, platelet activation, and systemic inflammation were noted in cancer patients with COVID-19. In contrast, complement activation increased in cancer patients with COVID-19 and elevated D-dimers. This was accompanied by decreased C1-Inhibitor levels in patients with D-dimers > 5 ug/ml FEU. Complement activation in cancer patients with COVID-19 is significantly increased in the setting of thromboinflammation. These findings support a link between coagulation and complement cascades in the setting of inflammation.
Sections du résumé
Background
COVID-19 pathology is associated with exuberant inflammation, vascular damage, and activation of coagulation. In addition, complement activation has been described and is linked to disease pathology. However, few studies have been conducted in cancer patients.
Objective
This study examined complement activation in response to COVID-19 in the setting of cancer associated thromboinflammation.
Methods
Markers of complement activation (C3a, C5a, sC5b-9) and complement inhibitors (Factor H, C1-Inhibitor) were evaluated in plasma of cancer patients with (n=43) and without (n=43) COVID-19 and stratified based on elevated plasma D-dimer levels (>1.0 μg/ml FEU). Markers of vascular endothelial cell dysfunction and platelet activation (ICAM-1, thrombomodulin, P-selectin) as well as systemic inflammation (pentraxin-3, serum amyloid A, soluble urokinase plasminogen activator receptor) were analyzed to further evaluate the inflammatory response.
Results
Increases in circulating markers of endothelial cell dysfunction, platelet activation, and systemic inflammation were noted in cancer patients with COVID-19. In contrast, complement activation increased in cancer patients with COVID-19 and elevated D-dimers. This was accompanied by decreased C1-Inhibitor levels in patients with D-dimers > 5 ug/ml FEU.
Conclusion
Complement activation in cancer patients with COVID-19 is significantly increased in the setting of thromboinflammation. These findings support a link between coagulation and complement cascades in the setting of inflammation.
Identifiants
pubmed: 34491250
doi: 10.3389/fimmu.2021.716361
pmc: PMC8416543
doi:
Substances chimiques
Biomarkers
0
Complement Inactivating Agents
0
Fibrin Fibrinogen Degradation Products
0
fibrin fragment D
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
716361Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
Copyright © 2021 Peerschke, Valentino, So, Shulman and Ravinder.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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