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

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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 cause‒effect relationships of vitamin C status, NET formation and IL-8 expression.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Thailand Science Research and Innovation Fund Chulalongkorn University (Grant Number HEA663000039).

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Authors and Affiliations

  1. Division of Nephrology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Chanunya Santiworakul, Nuanpan Siripen & Pornpimol Rianthavorn

  2. Center of Excellence On Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Wilasinee Saisorn & Asada Leelahavanichkul

  3. Interdisciplinary Program of Biomedical Sciences, Graduate School, Chulalongkorn University, Bangkok, Thailand

    Wilasinee Saisorn

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  1. Chanunya Santiworakul
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  5. Pornpimol Rianthavorn
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Contributions

All authors contributed to the conception and design of the study. Data collection and analysis were performed by Chanunya Santiworakul, Nuanpan Siripen, and Pornpimol Rianthavorn. Experimental design and interpretation were performed by Wilasinee Saisorn, Asada Leelahavanichkul and Pornpimol Rianthavorn. The first draft of the manuscript was written by Pornpimol Rianthavorn, and all authors commented on previous versions of the manuscript. All the authors have read and approved the final manuscript. All authors contributed to the writing, reviewing, and revising of this paper.

Corresponding author

Correspondence to Pornpimol Rianthavorn.

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Ethics approval

This study involving human participants was conducted in accordance with the ethical standards of the institutional and national research committee and with the Declaration of Helsinki of 1964 and its later amendments. The Human Research Ethics Committee of the Chulalongkorn University Faculty of Medicine approved this study (approval number 753/64).

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Written informed consent was obtained at the time of enrollment, and the data were kept anonymous.

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Santiworakul, C., Saisorn, W., Siripen, N. et al. Interleukin-8 and neutrophil extracellular traps in children with lupus nephritis and vitamin C deficiency. Pediatr Nephrol 39, 1135–1142 (2024). https://doi.org/10.1007/s00467-023-06189-1

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