Rheumatology International

, Volume 39, Issue 11, pp 1849–1857 | Cite as

Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus

  • Ivica JeremicEmail author
  • Olivera Djuric
  • Milos Nikolic
  • Marina Vlajnic
  • Aleksandra Nikolic
  • Dragica Radojkovic
  • Branka Bonaci-Nikolic
Observational Research


Neutrophil extracellular traps (NETs) are the main source of autoantigens in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the clinical importance of NETs-associated markers in SLE. We compared NETs-associated markers in SLE patients (n = 111) with healthy controls (n = 50). Moreover, in 35 patients with drug-naïve SLE (n = 35), we investigated correlation between NETs-associated markers [DNase I concentration, myeloperoxidase (MPO) activity, anti-MPO antibodies, cell-free DNA (cfDNA), NETolytic activity] with serological parameters [anti-dsDNA antibodies, C3, C4 and B-cell activating factor (BAFF) levels] and disease activity measured by modified SLE Disease Activity Index (M-SLEDAI-2K). In comparison with healthy controls, SLE patients had higher cfDNA, MPO activity, anti-MPO antibodies (p < 0.001), BAFF and DNase I concentration (p < 0.01). Contrary, NETolytic activity was lower in SLE patients (p < 0.05), despite higher concentration of DNase I. MPO activity and cfDNA levels showed correlation with DNase I concentration (p < 0.001, p < 0.01, respectively). BAFF levels correlated with cfDNA, DNase I concentration and MPO activity (p < 0.05). Anti-dsDNA antibodies showed correlation with MPO activity (p < 0.01), cfDNA and BAFF levels (p < 0.001). Anti-dsDNA and C3 levels were independent predictors of M-SLEDAI-2K in multivariate analysis (p < 0.01). We demonstrated that sera of SLE patients have decreased NETolytic activity, leading to increased levels of various NETs-associated markers, which correlate with anti-dsDNA antibodies in drug-naïve SLE. We showed that BAFF participates in a complex relationship between NETosis and anti-dsDNA antibodies production. These findings have important implications for a better understanding of SLE pathogenesis and development of therapy that inhibits NETs persistence and disease progression.


NET SLE DNase I Anti-dsDNA Cell-free DNA BAFF 


Author contributions

IJ and BBN designed study, performed clinical assessment, critically analyzed data and prepared the manuscript. OD performed the statistical analysis and prepared the manuscript for publication. MN analyzed data and prepared the manuscript. MV and IJ performed laboratory work and collected the data. AN and DR contributed to data analysis and critical revisions. All authors read and approved the final manuscript.


Supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, Grant No. 175065 and No. 173008.

Compliance with ethical standards

Conflict of interest

The Authors declare that there is no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Medicine, Institute of RheumatologyUniversity of BelgradeBelgradeSerbia
  2. 2.School of Medicine, Institute of EpidemiologyUniversity of BelgradeBelgradeSerbia
  3. 3.School of Medicine, Clinic of Dermatovenereology, Clinical Centre of SerbiaUniversity of BelgradeBelgradeSerbia
  4. 4.Institute of Molecular Genetics and Genetic EngineeringUniversity of BelgradeBelgradeSerbia
  5. 5.School of Medicine, Clinic of Allergy and ImmunologyUniversity of BelgradeBelgradeSerbia

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