Synovial Fluid Neutrophils From Patients With Juvenile Idiopathic Arthritis Display a Hyperactivated Phenotype

Mieke Metzemaekers, Bert Malengier-Devlies, Karen Yu, Sofie Vandendriessche, Jonas Yserbyt, Patrick Matthys, Lien De Somer, Carine Wouters, Paul Proost

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. The predominant subtypes, oligoarticular and polyarticular JIA, are traditionally considered to be autoimmune diseases with a central role for T cells and autoantibodies. Mounting evidence suggests an important role for neutrophils in JIA pathogenesis. We undertook this study to investigate the phenotypic features of neutrophils present in the blood and inflamed joints of patients.

METHODS: JIA synovial fluid (SF) and parallel blood samples from JIA patients and healthy children were collected. SF-treated neutrophils from healthy donors and pleural neutrophils from patients with pleural effusion were investigated as controls for SF exposure and extravasation. Multicolor flow cytometry panels allowed for in-depth phenotypic analysis of neutrophils, focusing on the expression of adhesion molecules, activation, and maturation markers and chemoattractant receptors. Multiplex technology was used to quantify cytokines in plasma and SF.

RESULTS: SF neutrophils displayed an activated, hypersegmented phenotype with decreased CD62L expression, up-regulation of adhesion molecules CD66b, CD11b, and CD15, and down-regulation of CXCR1/2. An elevated percentage of CXCR4-positive neutrophils was detected in SF from patients. Pleural neutrophils showed less pronounced maturation differences. Strikingly, significant percentages of SF neutrophils showed a profound up-regulation of atypical neutrophil markers, including CXCR3, intercellular adhesion molecule 1, and HLA-DR.

CONCLUSION: Our data show that neutrophils in inflamed joints of JIA patients have an activated phenotype. This detailed molecular analysis supports the notion that a complex intertwining between these innate immune cells and adaptive immune events drives JIA.

Original languageEnglish
Pages (from-to)875-884
Number of pages10
JournalArthritis & Rheumatology
Volume73
Issue number5
DOIs
Publication statusPublished - May 2021

Keywords / Materials (for Non-textual outputs)

  • Adaptive Immunity/immunology
  • Adolescent
  • Antigens, CD/metabolism
  • Arthritis, Juvenile/immunology
  • CD11b Antigen/metabolism
  • Cell Adhesion
  • Cell Adhesion Molecules/metabolism
  • Child
  • Child, Preschool
  • Down-Regulation
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins/metabolism
  • HLA-DR Antigens/immunology
  • Humans
  • Immunity, Innate/immunology
  • Immunophenotyping
  • Intercellular Adhesion Molecule-1/metabolism
  • L-Selectin/immunology
  • Lewis X Antigen/metabolism
  • Male
  • Neutrophil Activation/immunology
  • Neutrophils/immunology
  • Pleural Effusion
  • Receptors, CXCR3/immunology
  • Receptors, Interleukin-8A/immunology
  • Receptors, Interleukin-8B/immunology
  • Synovial Fluid/cytology
  • Up-Regulation

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