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The behavior of neutrophil extracellular traps and NADPH oxidative activity in pediatric systemic lupus erythematosus: relation to disease activity and lupus nephritis

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Abstract

Objectives

To evaluate the neutrophil extracellular traps (NETs) assay and NADPH oxidase (Nox2) activity in pediatric systemic lupus erythematosus (pSLE) in relation to each other and SLE characteristics.

Methods

This cross-sectional study included 50 children and adolescents with pSLE who were clinically evaluated and underwent routine laboratory work up of SLE (CBC, ESR, 24 hrs urinary proteins, serum creatinine, complement-3 (C3), anti-dsDNA, and antiphospholipid antibodies). NETs assay and dihydrorhodamine (DHR) test were done for patient group and 50 age- and sex-matched control group.

Results

The level of NETs was found significantly elevated among the patients (median 74.6 mU/ml) as compared to the controls (median 8.9 mU/ml) (p < 0.001), while values of DHR test were comparable between patients (median 95.5%) and controls (median 96.1%) (P = 0.55). There was a significant negative correlation between levels of NETs and DHR (p < 0.001). A significant positive correlation was noted between the 24 hrs urinary protein and NETs level (p < 0.001), but a significant negative correlation with DHR (p < 0.0001). Both NETs and DHR test values did not differ significantly between classes of lupus nephritis. NETs showed a significant positive correlation with anti-dsDNA titer (p = 0.004) and SLEDAI (p < 0.001), but a negative correlation with C3 (p < 0.001). DHR test was positively correlated with C3 levels (p = 0.003), but negatively correlated with anti-dsDNA titers (p = 0.008) and SLEDAI (p < 0.001).

Conclusion

NETs seem to have strong association with biomarkers of pSLE activity. On the other hand, Nox2 activity of the neutrophils was noted to be linked to quiescent state of SLE.

Key Points

• Neutrophils have displayed different actions in pSLE through the NETs and Nox2 activity.

• The inverse correlation between NETs and Nox2 activity makes the later a non-fundamental pathway for NETs formation.

• NETs are associated with pSLE flare and LN activity, while neutrophil Nox2 activity is related to disease remission.

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Authors and Affiliations

  1. Pediatric Allergy and Immunology Unit, Children’s Hospital, Ain Shams University, Cairo, Egypt

    Dalia Helmy El-Ghoneimy, Mohamed Hesham, Rasha Hasan & Sally Gouda

  2. Department of Clinical Pathology, Ain Shams University, Cairo, Egypt

    Mohamed Tarif

Authors
  1. Dalia Helmy El-Ghoneimy
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  2. Mohamed Hesham
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  3. Rasha Hasan
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  4. Mohamed Tarif
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  5. Sally Gouda
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Contributions

Dalia El-Ghoneimy: Study concept and design, analyzed the data, interpreted the results, and wrote the manuscript.

Mohamed Hesham: Contributed to analysis of the data, interpretation of the results, and drafting the manuscript.

Rasha Hasan: Contributed to analysis of the data, interpretation of the results, and drafting the manuscript.

Mohamed Tarif: Perform the laboratory work up of the study and contributed to drafting the manuscript.

Sally Gouda: Patients assessment and recruitment, contributed to interpretation of the results and drafting the manuscript.

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Correspondence to Dalia Helmy El-Ghoneimy.

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El-Ghoneimy, D.H., Hesham, M., Hasan, R. et al. The behavior of neutrophil extracellular traps and NADPH oxidative activity in pediatric systemic lupus erythematosus: relation to disease activity and lupus nephritis. Clin Rheumatol 38, 2585–2593 (2019). https://doi.org/10.1007/s10067-019-04547-9

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  • DOI: https://doi.org/10.1007/s10067-019-04547-9

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