Characterization of anti-neutrophil extracellular traps (NET) antibodies according to systemic lupus erythematosus clinical phenotypes.

Abstract

Anti-neutrophil extracellular traps (NETs) antibodies have been observed in patients with lupus nephritis and may contribute to the pathogenic role of NETs in patients with systemic lupus erythematosus (SLE). However, the prevalence of anti-NETs antibodies and their relationship with clinical features of patients with SLE have not been thoroughly studied, which is the aim of this study. Eighty-seven patients who fulfilled the 2019 EULAR/ACR Classification criteria for SLE were included. Plasmatic neutrophil elastase-DNA complexes as NETs remnants and the IgG anti-NETs antibodies were quantified by ELISA in the same sample. Thirty-one (35.6%) patients had positive anti-NETs antibodies. Patients with anti-NETs antibodies were younger at the time of recruitment (28.7 years (23.8-33.2) vs. 35.58 (27.88-45.77), p = 0.003) and had more prominent serological disease activity, with a higher prevalence of positive anti-double stranded (ds)-DNA antibodies (29 (93.5%) vs. 41 (73.2%), p = 0.022), higher titers (148.2 mg/dL vs. 35.6 mg/dL, p = 0.015), and lower levels of C3 and C4 (58 (37-85.5) vs. 77 (54-127), p = 0.017) and C4 (8 (8-12.5) vs. 20 (9-27), p < 0.001). From all clinical manifestations present at the time of recruitment, serositis showed a trend towards anti-NETs positivity (p 0.06). The global SLEDAI-2 K score was higher in the patient's IgG anti-NETs antibodies positive (13 (6.5-18) vs. 6 (4-15), p = 0.042). Anti-NETs antibodies were positively correlated with the systemic lupus erythematosus disease activity index (SLEDAI-2 K) score as well as with the titers of anti-dsDNA antibodies. IgG anti-NET antibodies were found in one-third of SLE patients. This is the first description of the association between IgG anti-NET and clinical features of SLE. Their characterization might allow us to address their role as potential novel biomarkers.