Neutrophil Extracellular Traps and DNASE balance in pre and post-treatment pediatric SLE patients 4076

Description Pediatric systemic lupus erythematosus (pSLE) is a multisystemic chronic autoimmune disease with high renal involvement. Neutrophil extracellular traps (NETs) are considered a potential source of self-antigen, leading to autoantibody production. NETs have also been shown to play a role in kidney pathology leading to lupus nephritis (LN). Low DNASE activity and mutations have been associated with lupus. Plasma was obtained from 18 pSLE treatment-naïve patients (before induction), 10 post-treatment patients and 12 age- and sex-matched healthy children. 67% of treatment naïve patients were diagnosed with biopsy proven LN. Induction was started at diagnosis with corticosteroids, primarily with mycophenolate, cyclophosphamide, or rituximab, depending on disease severity. Treatment response was measured by SELENA-SLEDAI score, dsDNA antibody levels, and urine protein/creatine ratios; all of which decreased post-treatment. Accumulation of NETs in circulation was observed pre-treatment with significant reductions post-treatment. Plasma from pre-treatment pSLE patients failed to degrade NETs efficiently which was restored after treatment. There was a defect in DNASE1 and DNASE1L3 activity pre-treatment. We observed an increase in anti-DNASE1L3 antibodies pretreatment which were significantly reduced post-treatment. Purified IgG from pre-treatment patients was able to inhibit DNASE1L3 activity whereas post-treatment IgG failed to do that. No DNASE1L3 RC206 mutation was detected Topic Categories Therapeutic Approaches to Autoimmunity (THER)