Anti-neutrophil extracellular trap antibodies in autoimmune rheumatic diseases: a suitable biomarker of thrombosis in systemic lupus erythematosus

Objectives: This case-control study aimed to elucidate the prevalence and role as biomarker of anti-neutrophil extracellular trap (anti-NET) antibodies in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic sclerosis (SSc). Methods: Serum samples from SLE, RA, SSc and healthy donors (HD) were evaluated for anti-NETs IgG, using an ELISA home-made coated with phorbol myristate acetate (PMA)-induced NET. Based on a positivity threshold set at the 99th percentile for HD sera, we calculated the positive samples. Results: We enrolled 349 patients with autoimmune rheumatic diseases (ARD), finding a prevalence of anti-NETs of about 40%. Of the 136 SLE patients 50 (36.8%) were anti-NETs positive, revealing an association between anti-NETs and antiphospholipid syndrome (APS) (OR 3.37 [95% CI 1.22-9.36], p=0.02) and with arterial thrombosis regardless of coexisting APS (OR 5.52 [95% CI 1.07-28.52], p=0.032). In RA patients 52 out 131 (39.7%) tested positive for anti-NETs and we found a significant association between testing positive for anti-NETs and the presence of ACPA (p=0.049). Of the 82 SSc patients enrolled 33 (40%) were anti-NETs positive, and we found a direct correlation with CCL-18 (r 0.289 [CI 95% 0.04-0.50], p=0.02), a biomarker of worst prognosis and mortality in ILD-SSc patients. Conclusions: In SLE patients, anti-NETs could have a role as a biomarker of thrombosis, a major cause of mortality in SLE.