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| Item Type: | Article |
|---|---|
| Title: | Discriminating promiscuous from target-specific autoantibodies in COVID-19 |
| Creators: |
Lebedin, M.  ORCID: https://orcid.org/0000-0002-3877-7195, Vazquez Garcia, C. ORCID: https://orcid.org/0000-0003-4583-7616, Spatt, L., Ratswohl, C. ORCID: https://orcid.org/0000-0001-5413-0730, Thibeault, C., Ostendorf, L. ORCID: https://orcid.org/0000-0003-3553-6406, Alexander, T. ORCID: https://orcid.org/0000-0003-1193-0097, Paul, F. ORCID: https://orcid.org/0000-0002-6378-0070, Sander, L.E., Kurth, F. and de la Rosa, K. ORCID: https://orcid.org/0000-0003-4809-3157
|
| 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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