Neutrophils extracellular traps formation may serve as a biomarker for disease activity in oligoarticular juvenile idiopathic arthritis: a pilot study

Merav Heshin-Bekenstein*, Szilvia Baron, Grant Schulert, Anna Shusterman, Victoria Fidel, Yoav Ben-Shahar, Rachel Shukrun, Yoav Binenbaum, Ronit Elhasid

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children, causing significant morbidity. Despite the dramatic improvement in treatment, many patients do not achieve complete remission, and biomarkers for subclinical disease, flares, and response to treatment are lacking. Neutrophils and neutrophil extracellular traps (NETs) play key roles in the pathogenesis of autoimmune and inflammatory conditions. In this study, we characterized neutrophil enzyme activity and NETs formation in oligoarticular and polyarticular JIA and explored their association with disease activity. Methods: Neutrophils from 6 healthy controls and 7 patients with oligoarticular and polyarticular JIA were freshly isolated at time of diagnosis and after glucocorticoid intra-articular injection. Enzymatic activity of neutrophil granular enzymes was monitored by colorimetry and PMA-activated NETs formation was assessed using fluorescent microscopy. Results: In this pilot and feasibility study, we revealed that NETs were significantly increased in oligoarticular JIA patients at time of diagnosis compared to healthy controls. Anti-inflammatory treatment using intra-articular steroid injection normalized NETs formation in these patients. Correlation between NETs formation and clinical Juvenile Activity Disease Activity Score-10 (cJADAS-10) was linear and significant (P = 0.007) in oligo but not in poly JIA patients. Conclusions: This is the first study exploring the link of NETs formation with oligo and poly JIA activity. We demonstrated a statistically significant linear correlation between cJADAS-10 and NETs formation in oligo but not in poly JIA patients. Hence, we suggest that NETs may reflect clinical disease activity in JIA, and may serve as a putative biomarker. Further work is needed to validate these initial results and determine the dynamics of NETs formation in JIA.

Original languageEnglish
Article number135
JournalArthritis Research and Therapy
Volume25
Issue number1
DOIs
StatePublished - Dec 2023

Keywords

  • Juvenile idiopathic arthritis (JIA)
  • Myeloperoxidase (MPO)
  • Neutrophil
  • Neutrophil elastase (NE)
  • Neutrophil extracellular traps (NETs)

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