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Discriminating promiscuous from target-specific autoantibodies in COVID-19

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Item Type:Article
Title:Discriminating promiscuous from target-specific autoantibodies in COVID-19
Creators Name:Lebedin, M., Vazquez Garcia, C., Spatt, L., Ratswohl, C., Thibeault, C., Ostendorf, L., Alexander, T., Paul, F., Sander, L.E., Kurth, F. and de la Rosa, K.
Abstract:Diverse autoantibodies were suggested to contribute to severe outcomes of COVID-19, but their functional implications are largely unclear. ACE2, the SARS-CoV-2 receptor and a key regulator of blood pressure, was described to be one of many targets of autoantibodies in COVID-19. ACE2 in its soluble form (sACE2) is highly elevated in the blood of critically ill patients, raising the question of whether sACE2:spike complexes induce ACE2 reactivity. Screening 247 COVID-19 patients, we observed elevated sACE2 and anti-ACE2 IgG that poorly correlated. Interestingly, levels of IgGs recognizing ACE2, IFNα2, and CD26 strongly correlated in severe COVID-19, with 15% of sera showing polyreactivity versus 4.1% exhibiting target-directed autoimmunity. Promiscuous autoantibodies failed to impair the activity of ACE2 and IFNα2, while only specific anti-IFNα2 IgG compromised cytokine function. Our study suggests that the detection of autoantibodies in COVID-19 is often attributed to a promiscuous reactivity, potentially misinterpreted as target-specific autoimmunity with functional impact.
Keywords:Autoantibodies, COVID-19, SARS-CoV-2, Autoimmunity, Autoreactivity
Source:European Journal of Immunology
ISSN:0014-2980
Publisher:Wiley
Volume:53
Number:5
Page Range:e2250210
Date:May 2023
Official Publication:https://doi.org/10.1002/eji.202250210
PubMed:View item in PubMed

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