The study investigates the role of neutrophil extracellular traps (NETs) in the pathogenesis of lupus nephritis in systemic lupus erythematosus (SLE) patients. NETs, composed of DNA, histones, and neutrophil proteins, are antimicrobial structures released by neutrophils in response to infections. The timely removal of NETs is crucial for tissue homeostasis to avoid the presentation of self-antigens. The researchers found that serum endonuclease DNase1 is essential for the degradation of NETs. However, a subset of SLE patients' sera showed poor degradation of NETs due to either the presence of DNase1 inhibitors or anti-NET antibodies that prevent DNase1 access to NETs. Impairment of DNase1 function and failure to dismantle NETs correlated with kidney involvement in SLE. The study suggests that identifying SLE patients who cannot clear NETs might be a useful indicator of renal involvement and that targeting NETs could be a therapeutic approach in SLE.The study investigates the role of neutrophil extracellular traps (NETs) in the pathogenesis of lupus nephritis in systemic lupus erythematosus (SLE) patients. NETs, composed of DNA, histones, and neutrophil proteins, are antimicrobial structures released by neutrophils in response to infections. The timely removal of NETs is crucial for tissue homeostasis to avoid the presentation of self-antigens. The researchers found that serum endonuclease DNase1 is essential for the degradation of NETs. However, a subset of SLE patients' sera showed poor degradation of NETs due to either the presence of DNase1 inhibitors or anti-NET antibodies that prevent DNase1 access to NETs. Impairment of DNase1 function and failure to dismantle NETs correlated with kidney involvement in SLE. The study suggests that identifying SLE patients who cannot clear NETs might be a useful indicator of renal involvement and that targeting NETs could be a therapeutic approach in SLE.