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. Veenith, Tonny 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.
Veenith, Tonny
Thwaites, Ryan S.
Openshaw, Peter J. M.
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2023-05-18
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Abstract
Post-acute cardiac sequelae, following SARS-CoV-2 infection, are well recognised 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 analysed 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 hospitalised 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.
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Ward KE, Steadman L, Karim AR, Reynolds GM, Pugh M, Chua W, Faustini SE, Veenith T, Thwaites RS, Openshaw PJM, Drayson MT, Shields AM, Cunningham AF, Wraith DC, Richter AG. SARS-CoV-2 infection is associated with anti-desmoglein 2 autoantibody detection. Clin Exp Immunol. 2023 Jul 21;213(2):243-251. doi: 10.1093/cei/uxad046.
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