Interleukin-8 and neutrophil extracellular traps in children with lupus nephritis and vitamin C deficiency.

Abstract

Vitamin C is a potent scavenger of reactive oxygen species, which induce neutrophil extracellular trap (NET) formation. NETs are a major source of autoantigens and are involved in systemic lupus erythematosus (SLE) pathogenesis. We determined vitamin C status and evaluated NET formation and inflammatory cytokines in children with lupus nephritis. Serum vitamin C was measured in 46 patients (82.6% females, mean age 14.5 ± 0.3years). Vitamin C levels < 0.3mg/dL indicated vitamin C deficiency. Patients were divided into two groups according to serum vitamin C levels: normal and low (< 0.3mg/dL). We compared NET formation and levels of SLE-related cytokines, including interleukin (IL)-8, IL-10, and tumor necrosis factor-α (TNF-α), between groups. NET formation was determined through measurement of serum citrullinated histone 3 levels and mRNA expression of peptidyl arginine deiminase-4 and assessment of the percentage of neutrophils with NETs by immunofluorescence. Nine patients (19.6%) had vitamin C deficiency. Kidney pathology assessment at disease onset revealed that histological activity index and number of kidney biopsies containing crescentic glomeruli were higher in vitamin C-deficient patients, but chronicity index was not. NET formation and serum IL-8 were more prominent in vitamin C-deficient patients. Serum IL-8 levels were 12.9 ± 5.2pg/mL in low vitamin C group and 5.2 ± 0.9pg/mL in normal vitamin C group (p = 0.03). Serum IL-10 and TNF-α were similar between groups. Our study demonstrated correlation among vitamin C deficiency, increased NET formation, and IL-8 upregulation in children with lupus nephritis. A prospective study is required to evaluate cause‒effect relationships of vitamin C status, NET formation and IL-8 expression.