Background/Purpose: Pediatric systemic lupus erythematosus (pSLE) is a multisystemic chronic autoimmune disease with high renal involvement. In SLE, neutrophil extracellular traps (NETs) are considered a potential source of antigen, leading to autoantibody production. NETs activate plasmacytoid dendritic cells to produce high levels of interferon-α, a known driver of lupus pathogenesis. NETs have also been shown to play a role in kidney pathology leading to lupus nephritis (LN).Also, low DNase activity and mutations in DNASEIL3 have been associated with lupus. We hypothesized that NETs will be elevated in pediatric lupus and our study aims to investigate levels of circulating NETs in pSLE as compared to healthy children (pHC) and further elucidate mechanisms contributing to NET accumulation.

Methods: Plasma was obtained from 13 pSLE patients who were either treatment-naïve or not on corticosteroids at the time of enrollment and 12 pHC. Lupus disease activity was measured using SELENA-SLEDAI. ELISA and smear assay were used to detect NETs in plasma samples. DNASE1L3 concentration was measured using ELISA and DNase1L3 enzymatic activity was assayed by digestion of chromatin in purified nuclei. The ability of plasma to degrade NETs was measured using NET degradation assay.

Results: 10/13 of pSLE patients were female, with a mean of 13±4.4years, and a mean SLEDAI score of 13.8±8.1. 7/13 patients had biopsy-proven proliferative LN. Significantly higher levels of circulating NETs were found in pSLE plasma which positively correlated with measures of disease activity and anti-ds DNA titers (Figure 1). Plasma from pSLE failed to degrade NETs efficiently. Although DNASE1L3 levels were higher in pSLE patients, DNASE1L3 activity was reduced, as compared to healthy children. Moreover, higher anti-NET protective antibodies were found in pSLE plasma.

Conclusion: These data suggest that defective functional DNASE1L3 activity and increased anti-NET protective antibodies could lead to delayed clearance and accumulation of NETs in pSLE plasma.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduced-dnase1l3-activity-and-increased-anti-net-protective-antibodies-contributes-to-accumulation-of-neutrophil-extracellular-traps-in-pediatric-sle-patients/