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NET Formation in Systemic Lupus Erythematosus: Changes during the COVID-19 Pandemic
Jasmin Knopf1,2, Johanna Sjöwall3, Martina Frodlund4
1Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
Insights
Neutrophil extracellular traps (NETs) and NET activity changed significantly in patients with systemic lupus erythematosus (SLE) during the pandemic, independent of SARS-CoV-2 exposure. This finding impacts understanding of autoimmune disease flares.
Area of Science:
- Immunology
- Rheumatology
- Infectious Diseases
Background:
- COVID-19 severity is linked to immune dysregulation, raising concerns for autoimmune patients on immunosuppressants.
- Thromboembolism is a complication of COVID-19 and systemic lupus erythematosus (SLE), potentially involving neutrophil extracellular traps (NETs).
- Imbalances in NET formation and clearance may worsen autoimmune conditions like SLE.
Purpose of the Study:
- To assess NET formation markers in SLE patients before and during the COVID-19 pandemic.
- To correlate NET formation with clinical parameters in SLE patients.
- To determine if SARS-CoV-2 exposure influences NET formation in SLE.
Main Methods:
- Assessed neutrophil elastase (NE) activity, cell-free DNA, MPO-DNA, and NE-DNA complexes in pre-pandemic and pandemic serum samples from SLE patients.
- Correlated NET markers with clinical parameters including blood cell counts and complement levels.
- Analyzed serologic evidence of SARS-CoV-2 exposure.
Main Results:
- Significant differences in NE-DNA complexes and NE activity were observed between pre-pandemic and pandemic serum samples.
- NE activity correlated with hemoglobin, blood cell counts, and complement levels (C3, C4) pre-pandemic.
- During the pandemic, NE activity correlated only with leukocyte and neutrophil counts.
- These changes in NE activity occurred independently of SARS-CoV-2 exposure.
Conclusions:
- NET formation, specifically NE activity, appears to change in SLE patients during the pandemic.
- These alterations in NET activity are not solely driven by SARS-CoV-2 infection or exposure.
- Findings suggest a potential link between pandemic-related factors and NET dysregulation in SLE, impacting disease activity.
Abstract:
The severity of the coronavirus disease in 2019 (COVID-19) is strongly linked to a dysregulated immune response. This fuels the fear of severe disease in patients with autoimmune disorders continuously using immunosuppressive/immunomodulating medications. One complication of COVID-19 is thromboembolism caused by intravascular aggregates of neutrophil extracellular traps (NETs) occluding the affected vessels. Like COVID-19, systemic lupus erythematosus (SLE) is characterized by, amongst others, an increased risk of thromboembolism. An imbalance between NET formation and clearance is suggested to play a prominent role in exacerbating autoimmunity and disease severity. Serologic evidence of exposure to SARS-CoV-2 has a minor impact on the SLE course in a Swedish cohort reportedly. Herein, we assessed NET formation in patients from this cohort by neutrophil elastase (NE) activity and the presence of cell-free DNA, MPO-DNA, and NE-DNA complexes and correlated the findings to the clinical parameters. The presence of NE-DNA complexes and NE activity differed significantly in pre-pandemic versus pandemic serum samples. The latter correlated significantly with the hemoglobin concentration, blood cell counts, and complement protein 3 and 4 levels in the pre-pandemic but only with the leukocyte count and neutrophil levels in the pandemic serum samples. Taken together, our data suggest a change, especially in the NE activity independent of exposure to SARS-CoV-2.
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