Jeremic, Ivica (36016708800)Ivica (36016708800)JeremicDjuric, Olivera (56410787700)Olivera (56410787700)DjuricNikolic, Milos (56910382000)Milos (56910382000)NikolicVlajnic, Marina (57194184351)Marina (57194184351)VlajnicNikolic, Aleksandra (57194842918)Aleksandra (57194842918)NikolicRadojkovic, Dragica (6602844151)Dragica (6602844151)RadojkovicBonaci-Nikolic, Branka (10839652200)Branka (10839652200)Bonaci-Nikolic2025-07-022025-07-022019https://doi.org/10.1007/s00296-019-04426-1https://www.scopus.com/inward/record.uri?eid=2-s2.0-85070999809&doi=10.1007%2fs00296-019-04426-1&partnerID=40&md5=d127e1b13c16c8c9bece047d35335a8ehttps://remedy.med.bg.ac.rs/handle/123456789/12604Neutrophil 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. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.Anti-dsDNABAFFCell-free DNADNase INETSLE