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Item Type: | Article |
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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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