Antibodies against neutrophil extracellular traps (NETs) potentiate clinical performance of anti-double-stranded DNA antibodies in systemic lupus erythematosus

Autoantibodies against NETs (ANETA) are present in SLE patients. We aimed to determine the clinical relevance of ANETA in SLE. Serum from 129 SLE patients, 161 patients with various rheumatoid diseases (DC), and 53 healthy controls (HC) were tested by a home-made ANETA ELISA platform. ANETA showed a sensitivity of 35.7% and a specificity of 92.5%, respectively, in the diagnosis of SLE. The combination of ANETA with anti-dsDNA antibody increased the diagnostic sensitivity from 49.6% to 62.8% for SLE. The presence of ANETA potentiates the clinical utility of anti-dsDNA antibodies in identifying a subset of SLE patients with higher disease activity and hematological abnormalities. The binding of ANETA to NETs did not inhibit the immunostimulatory effect of NETs. Our findings suggested that ANETA have potential as clinically relevant biomarkers that potentiate the clinical performance of anti-dsDNA antibodies in the diagnosis, risk stratification and subtyping of patients with SLE.