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NETosis-Related Biomarkers in Systemic Lupus Erythematosus, Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing
Mark M Melamud1, Anna S Tolmacheva1, Alexey E Sizikov1,2
1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
International Journal of Molecular Sciences
|December 30, 2025
Summary
NETosis, a form of cell death, shows distinct biomarker patterns in rheumatic diseases. Systemic lupus erythematosus (SLE) exhibits the most significant NETosis signs, while psoriatic arthritis (PsA) and ankylosing spondylitis (AS) show increased cell-free DNA.
Area of Science:
- Rheumatology and Immunology
- Cellular Biology
- Biomarker Discovery
Background:
- NETosis is implicated in rheumatic diseases like SLE, RA, PsA, and AS.
- Circulating NETosis biomarker levels and their disease-specific changes require further clarification.
Purpose of the Study:
- To investigate and compare NETosis markers (cfDNA, MPO, H3cit) across SLE, RA, PsA, and AS.
- To identify disease-specific NETosis profiles and associations with clinical factors.
Main Methods:
- Quantification of total, nuclear, and mitochondrial cell-free DNA (cfDNA).
- Measurement of myeloperoxidase (MPO) and citrullinated histone H3 (H3cit) as specific NETosis markers.
- Statistical analysis (ANCOVA) adjusting for sex, age, and disease duration.
Main Results:
- Elevated total cfDNA in SLE and AS; nuclear and mitochondrial cfDNA increased in all four diseases.
- Significantly higher MPO and H3cit in SLE, with MPO also elevated in RA.
- SLE patients with high MPO/H3cit had co-existing cardiovascular diseases; biological therapy affected mitochondrial cfDNA, MPO, and H3cit.
Conclusions:
- Distinct NETosis marker profiles characterize SLE, RA, PsA, and AS.
- SLE shows the most pronounced NETosis activity, followed by RA.
- cfDNA increases are prominent in PsA and AS, suggesting different pathogenic roles of NETosis.

