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SARS-CoV-2 infection is associated with anti-desmoglein 2 autoantibody detection
Ward, Kerensa E Steadman, Lora Karim, Abid R Reynolds, Gary M Pugh, Matthew Chua, Winnie Faustini, Sian E Thwaites, Ryan S Openshaw, Peter J M
Ward, Kerensa E
Steadman, Lora
Karim, Abid R
Reynolds, Gary M
Pugh, Matthew
Chua, Winnie
Faustini, Sian E
Thwaites, Ryan S
Openshaw, Peter J M
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Epub Date
Issue Date
2023-04-24
Submitted date
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Abstract
Post-acute cardiac sequelae, following SARS-CoV-2 infection, are well recognized as complications of COVID-19. We have previously shown the persistence of autoantibodies against antigens in skin, muscle, and heart in individuals following severe COVID-19; the most common staining on skin tissue displayed an inter-cellular cement pattern consistent with antibodies against desmosomal proteins. Desmosomes play a critical role in maintaining the structural integrity of tissues. For this reason, we analyzed desmosomal protein levels and the presence of anti-desmoglein (DSG) 1, 2, and 3 antibodies in acute and convalescent sera from patients with COVID-19 of differing clinical severity. We find increased levels of DSG2 protein in sera from acute COVID-19 patients. Furthermore, we find that DSG2 autoantibody levels are increased significantly in convalescent sera following severe COVID-19 but not in hospitalized patients recovering from influenza infection or healthy controls. Levels of autoantibody in sera from patients with severe COVID-19 were comparable to levels in patients with non-COVID-19-associated cardiac disease, potentially identifying DSG2 autoantibodies as a novel biomarker for cardiac damage. To determine if there was any association between severe COVID-19 and DSG2, we stained post-mortem cardiac tissue from patients who died from COVID-19 infection. This confirmed DSG2 protein within the intercalated discs and disruption of the intercalated disc between cardiomyocytes in patients who died from COVID-19. Our results reveal the potential for DSG2 protein and autoimmunity to DSG2 to contribute to unexpected pathologies associated with COVID-19 infection.
Citation
Kerensa E Ward, Lora Steadman, Abid R Karim, Gary M Reynolds, Matthew Pugh, Winnie Chua, Sian E Faustini, Tonny Veenith, Ryan S Thwaites, Peter J M Openshaw, Mark T Drayson, Adrian M Shields, Adam F Cunningham, David C Wraith, Alex G Richter, SARS-CoV-2 infection is associated with anti-desmoglein 2 autoantibody detection, Clinical and Experimental Immunology, Volume 213, Issue 2, August 2023, Pages 243–251, https://doi.org/10.1093/cei/uxad046
Publisher
Research Unit
PubMed ID
37095599 (pubmed)
PubMed Central ID
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Type
Journal article
Language
en
Description
© 2023 The Authors. Published by Oxford University Press. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1093/cei/uxad046
Series/Report no.
ISSN
0009-9104
EISSN
1365-2249
ISBN
ISMN
Gov't Doc #
Sponsors
This study was funded as part of the UK Coronavirus Immunology Consortium funded by NIHR and UKRI. This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. Post-mortem sample collection was funded by an MRC Clinical Research Training Fellowship and the Welsh Assembly Government.
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Licence for published version: Creative Commons Attribution 4.0 International