Immunometabolic Analysis of Synovial Fluid from Juvenile Idiopathic Arthritis Patients

Area of Science:

• Rheumatology
• Immunology
• Cell Biology

Background:

• Juvenile idiopathic arthritis (JIA) is a rheumatic disease characterized by joint inflammation.
• Polymorphonuclear neutrophils (PMNs) infiltrate JIA synovial fluid (SF), exhibiting variable frequencies and altered functions.
• Previous studies indicated SF PMNs in JIA have high exocytic but low phagocytic and immunoregulatory activities.

Purpose of the Study:

• To investigate the association between synovial fluid neutrophilia and immune responses in JIA.
• To determine if varying PMN levels in JIA SF correlate with specific immune cell phenotypes and mediator profiles.

Main Methods:

• Collected synovial fluid (SF) and blood from 16 adolescent JIA patients.
• Analyzed SF and blood leukocytes using flow cytometry.
• Quantified immune mediators and performed metabolomics on SF and plasma.
• Assessed immunoregulatory capacity by culturing healthy donor T cells in JIA SF.

Main Results:

• JIA SF showed bimodal distributions of PMN and T cell frequencies, defining PMN-high/T cell-low (PMNHigh) and PMN-low/T cell-high (PMNLow) groups.
• Pro-inflammatory mediators were elevated in JIA SF compared to plasma, with further increases in PMNHigh SF.
• SF PMNs displayed increased exocytosis and PD-1/PD-L1 expression; SF PMNs and monocytes/macrophages showed increased arginase-1.
• Monocyte/macrophage subpopulations coexpressing PD-1 and PD-L1 were identified in JIA SF, with higher expression in PMNHigh SF.
• Healthy donor T cells exhibited reduced coreceptor expression when stimulated in PMNHigh SF versus PMNLow SF.

Conclusions:

• PMN predominance in JIA SF is linked to elevated immune mediator concentrations.
• High PMN levels in JIA SF may influence monocyte/macrophage phenotype and T cell activation.
• The study did not find differences in immunoregulatory amino acid metabolites between PMNHigh and PMNLow groups.