Neutrophil extracellular traps as a potential marker of systemic lupus erythematosus activity

The heterogeneity of systemic lupus erythematosus (SLE) poses a significant challenge in identifying biomarkers for assessing disease activity. Currently, there is a paucity of established biomarkers capable of evaluating SLE flares. This study aimed to identify novel biomarkers that exhibit improved diagnostic accuracy in assessing SLE activity.

A cross-sectional study was conducted at Zhongshan Hospital Xiamen University from August 2021 to April 2024,enrolling 118 patients with SLE, including 81 cases of active SLE, 50 cases of active lupus nephritis (LN) and 30 cases of active non-LN. The objective was to evaluate the diagnostic accuracy of novel biomarker called Neutrophil Extracellular Traps(NETs) for SLE activity and analyze its correlations with conventional biomarkers such as complement C3, C4, and anti-dsDNA.

Serum NETs levels were significantly elevated in patients with active SLE and active LN(P < 0.001). Furthermore, positive correlations were observed between NETs levels and disease activity score based on Systemic Lupus Erythematosus Disease Activity Index-2 K (SLEDAI-2 K) (r = 0.64, P < 0.001), as well as anti-dsDNA antibody (r = 0.54, P < 0.001).Conversely, the NETs levels were negativity correlated with complement C3 concentration (r = -0.50, P < 0.001), as well as C4 concentration (r = -0.34,P < 0.001). Univariate and multivariate analysis revealed two biomarkers performed statistical significance: NETs (OR = 6.802, 95 %CI: 2.414-19.167,P < 0.001) and anti-dsDN A(OR = 3.95,95 %CI:1.582-9.864, P = 0.003). NETs had the highest AUC of 0.82(P < 0.001), with a cut-off at 515.47 ng/L demonstrating 61.63 % sensitivity and 96.87 % specificity. For the active LN group, the AUC was found to be 0.97 (P < 0.001), with a cutoff value of 515.47 ng/L, sensitivity of 100 %, and specificity of 59.76 %. Moreover, the active non-LN group had AUC of 0.70 (P = 0.007), with the same cutoff value, sensitivity of 89.61 %, and specificity of 51.61 %.

In contrast to conventional laboratory markers, serum NETs represent a novel diagnostic marker for assessing disease activity in SLE, demonstrating promising potential for clinical application.