ABSTRACT
BACKGROUND: 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. METHODS: Serum vitamin C was measured in 46 patients (82.6% females, mean age 14.5 ± 0.3 years). Vitamin C levels < 0.3 mg/dL indicated vitamin C deficiency. Patients were divided into two groups according to serum vitamin C levels: normal and low (< 0.3 mg/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. RESULTS: 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 ± 5.2 pg/mL in low vitamin C group and 5.2 ± 0.9 pg/mL in normal vitamin C group (p = 0.03). Serum IL-10 and TNF-α were similar between groups. CONCLUSIONS: 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 causeâeffect relationships of vitamin C status, NET formation and IL-8 expression.
Subject(s)
Ascorbic Acid Deficiency , Extracellular Traps , Interleukin-8 , Lupus Erythematosus, Systemic , Lupus Nephritis , Adolescent , Child , Female , Humans , Male , Ascorbic Acid , Ascorbic Acid Deficiency/complications , Cytokines/metabolism , Extracellular Traps/metabolism , Interleukin-10/metabolism , Interleukin-8/metabolism , Lupus Erythematosus, Systemic/metabolism , Lupus Erythematosus, Systemic/pathology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
PURPOSE: Adolescents with systemic lupus erythematosus (SLE) are susceptible to sleep impairments. We aimed to determine the prevalence and factors related to sleep impairments, and the associations of sleep impairments with health-related quality of life (HRQOL) in Thai adolescents with SLE. METHODS: Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire for Adolescents (PHQA), and Pediatric Quality of Life Inventory™ 4.0 Core Scales were administered to 57 participants with SLE aged 13-18 years to evaluate sleep, depression, and HRQOL, respectively. Participants were divided into "good sleep" (PSQI scores <5) and "poor sleep" groups (PSQI scores ≥5). Participants with body mass index (BMI) >23 kg/m2 were classified into the high BMI group. FINDINGS: Eighteen participants (31.6%) were in the poor sleep group. High BMI and PHQA scores were associated with sleep impairments with the odds ratio of 8.00 (95% CI 1.50-42.64; p = 0.02), and 1.25 (95% CI 1.01-1.54; p = 0.04), respectively. In terms of HRQOL, adolescents with SLE had the highest scores in social functioning and the lowest scores in school functioning. Good sleepers had better scores than poor sleepers across all sub-categories except for social functioning, and the difference was significant in emotional functioning (90% (IQR 75-100) vs. 70% (IQR 55-85); p = 0.03). CONCLUSIONS: A substantial number of adolescents with SLE had sleep impairments, which decreased HRQOL, particularly in emotional functioning. Sleep impairments were associated with obesity and depression. IMPLICATIONS: Proactive management in addressing weight, mood, and sleep problems should be included in the multidisciplinary care of adolescents with SLE to improve their health and well-being.
