Neutrophil extracellular traps and oxidative stress in systemic lupus erythematosus patients with and without renal involvement

Objectives: To investigate the levels of plasma neutrophil extracellular traps (NETs) and free thiols, the latter reflecting systemic oxidative stress (OS), and to explore the relationship between NETs and OS in quiescent systemic lupus erythematosus (SLE) patients with and without renal involvement. Methods: Plasma levels of NETs and free thiols were measured cross-sectionally in 100 SLE patients with low disease activity (SLEDAI < 5), of whom 73 patients had no renal involvement (non-LN) and 27 patients had lupus nephritis (LN). Additionally, 22 healthy controls (HCs) were included. NETs were measured using a myeloperoxidase-DNA complex ELISA and free thiols were measured using a thiol assay kit. Results: NETs levels were significantly higher in both non-LN and LN patients compared to HCs (p < 0.001, p = 0.013), with no difference between the two patient groups (p = 0.799). Free thiol levels were not significantly different between groups. Interestingly, NETs were negatively correlated with free thiols in all 100 SLE patients (rho = -0.32) and non-LN patients (rho = -0.38), but not in LN patients. Levels of free thiols were significantly lower in subgroups of patients with estimated glomerular filtration rate (eGFR) < 60, serum creatinine (sCr) ≥ 90, C reactive protein (CRP) levels ≥ 5 and body mass index (BMI) ≥ 30. In multivariable regression, disease duration, NETs levels, and eGFR were independently associated with free thiol levels. Conclusions: Levels of NETs were increased in quiescent SLE patients. Although free thiol levels did not differ among the groups. The levels of NETs and free thiols were independently associated in SLE patients, suggesting a potential role of OS in NETs formation. Therefore, reducing OS might be an additional therapeutic target for SLE treatment.