期刊
JCI INSIGHT
卷 6, 期 15, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.150111
关键词
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资金
- career development grants from the Rheumatology Research Foundation
- Arthritis National Research Foundation
- APS ACTION
- VA Healthcare System
- Intramural Research Program of the NIH
- NHLBI
- Lasker Foundation
- Falk Medical Research Trust Catalyst Award
- JOBST-American Venous Forum Award
- NIH [R01HL115138]
- Lupus Research Alliance
- Burroughs Wellcome Fund
- University of Michigan Frankel Cardiovascular Center Ignitor Award
- A. Alfred Taubman Medical Research Institute
- Rheumatology Research Foundation
The presence of autoantibodies targeting neutrophil extracellular traps (NETs) in individuals hospitalized with severe COVID-19 may impair NET clearance, exacerbating SARS-CoV-2-mediated thromboinflammation.
The release of neutrophil extracellular traps (NETs) by hyperactive neutrophils is recognized to play an important role in the thromboinflammatory milieu inherent to severe presentations of COVID-19. At the same time, a variety of functional autoantibodies have been observed in individuals with severe COVID-19, where they likely contribute to immunopathology. Here, we aimed to determine the extent to which autoantibodies might target NETs in COVID-19 and, if detected, to elucidate their potential functions and clinical associations. We measured anti-NET antibodies in 328 individuals hospitalized with COVID-19 alongside 48 healthy controls. We found high anti-NET activity in the IgG and IgM fractions of 27% and 60% of patients, respectively. There was a strong correlation between anti-NET IgG and anti-NET IgM. Both anti-NET IgG and anti-NET IgM tracked with high levels of circulating NETs, impaired oxygenation efficiency, and high circulating D-dimer. Furthermore, patients who required mechanical ventilation had a greater burden of anti-NET antibodies than did those not requiring oxygen supplementation. Levels of anti-NET IgG (and, to a lesser extent, anti-NET IgM) demonstrated an inverse correlation with the efficiency of NET degradation by COVID-19 sera. Furthermore, purified IgG from COVID-19 sera with high levels of anti-NET antibodies impaired the ability of healthy control serum to degrade NETs. In summary, many individuals hospitalized with COVID-19 have anti-NET antibodies, which likely impair NET clearance and may potentiate SARS-CoV-2-mediated thromboinflammation.
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