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. 2022 Jul 22;12(1):12523.
doi: 10.1038/s41598-022-15969-y.

Anti-cardiolipin IgG autoantibodies associate with circulating extracellular DNA in severe COVID-19

Daniel Bertin #  1 , Alexandre Brodovitch #  2 , Alexandre Lopez  3 , Robin Arcani  4   5 , Grace M Thomas  5 , Abdou Beziane  2 , Samuel Weber  2 , Benjamin Babacci  2 , Xavier Heim  2   5 , Louise Rey  2 , Marc Leone  3 , Jean Louis Mege  2   6 , Nathalie Bardin  7   8
Affiliations

Anti-cardiolipin IgG autoantibodies associate with circulating extracellular DNA in severe COVID-19

Daniel Bertin et al. Sci Rep. .

Abstract

Whereas the detection of antiphospholipid autoantibodies (aPL) in COVID-19 is of increasing interest, their role is still unclear. We analyzed a large aPL panel in 157 patients with COVID-19 according to the disease severity. We also investigated a potential association between aPL and extracellular DNA (exDNA, n = 85) or circulating markers of neutrophil extracellular traps (NET) such as citrullinated histones H3 (CitH3, n = 49). A total of 157 sera of patients infected by SARS-CoV-2 were collected. A large aPL panel including lupus anticoagulant, anti-cardiolipin and anti-beta-2 glycoprotein I (IgG, IgM and IgA), anti-phosphatidylethanolamine IgA, anti-prothrombin (IgG and IgM) was retrospectively analyzed according to the disease severity. We found a total aPL prevalence of 54.8% with almost half of the cases having aCL IgG. Within an extended panel of aPL, only aCL IgG were associated with COVID-19 severity. Additionally, severe patients displayed higher CitH3 levels than mild patients. Interestingly, we highlighted a significant association between the levels of aCL IgG and exDNA only in aCL positive patients with severe disease. In conclusion, we showed a significant link between aPL, namely aCL IgG, and circulating exDNA in patients with severe form of COVID-19, that could exacerbate the thrombo-inflammatory state related to disease severity.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Flow Chart of patients. ARDS acute respiratory distress syndrome, ICU Intensive Care Unit. Two comparison were performed in this study: one between severe and mild COVID groups (*) and another between COVID ICU and non COVID ICU groups (**).
Figure 2
Figure 2
Antiphospholipid autoantibody levels in mild and severe patients with COVID-19. aCL anti-cardiolipin, aB2GPI anti-beta-2 glycoprotein I, aPE anti-phosphatidylethanolamine, aPT anti-prothrombin autoantibodies. Statistical analysis performed with Student's t test. ns not significant.
Figure 3
Figure 3
Extracellular DNA and citrullinated histones H3 levels in patients with COVID-19. Extracellular DNA levels in mild/severe COVID-19 patients (a) and in aCL IgG positive (Pos)/negative (Neg) patients with severe COVID-19 (b). Citrullinated histones H3 levels in mild /severe COVID-19 patients (c) and in aCL IgG positive (Pos)/negative (Neg) with severe COVID-19 (d). Statistical analysis performed with Student's t test. aCL anti-cardiolipin, ns not significant.
Figure 4
Figure 4
Putative mechanism of anticardiolipin autoantibodies in COVID-19 severity. We hypothesize that SARS-CoV-2 infection of genetically-prone patients results in autoimmunity. Anticardiolipin autoantibodies (aCL) can bind a cell surface complex composed of lysobiphosphatidic acid (LBPA) and endothelial protein C receptor (EPCR). This interaction promotes cell death via reactive oxygen species (ROS). Then, releases extracellular DNA contributes to a heightened thrombo-inflammatory state associated with COVID-19 severity. The figure has been drawn by AB using InkScape 0.92, http://www.inkscape.org.
See this image and copyright information in PMC

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