Cross-Sectional and Longitudinal Immunoprofiling of Oligoarticular Juvenile Idiopathic Arthritis Reveals Different Patterns in Synovial Fluid and Plasma.

Abstract

Oligoarticular juvenile idiopathic arthritis (oligoJIA) constitutes nearly 60% of all JIA cases. The immune mechanisms involved in the pathogenesis remain incompletely understood. Few proteomic studies have been performed using synovial fluid (SF) samples. We conducted an exploratory analysis of plasma and SF samples to define inflammatory profiles, assess plasma-SF correlation and examine longitudinal variations. Using proximity extension assay (PEA), we profiled 92 immune-related proteins in plasma and Sf from 14 oligoJIA patients (untreated or NSAID-treated) and plasma from 28 age and sex-matched healthy controls. Differentially expressed proteins were analysed using gene ontology (GO) and KEGG pathways via STRING. Plasma proteomic immune profiles from oligoJIA patients were highly overlapping with immune profiles of healthy donors. Six proteins were differentially expressed between the two groups. Overall, plasma and SF protein expressions correlated (r = 0.78), mainly driven by 13 proteins including CCL25, FGF21 and KITLG. However, the differentially expressed proteins in plasma did not correlate with those in SF. Longitudinal analysis of 20 SF and 10 plasma samples from one patient revealed immunosuppressive effects of methotrexate (MTX) with distinct kinetics in plasma and SF. Paired SF samples from five patients revealed that cell chemotaxis was a key feature in early disease, distinguishing it from the persistent phase. Immunoprofiling of SF from patients with oligoJIA identified more disease-relevant characteristics than analysis of plasma samples. Several proteins, but not all, correlated between plasma and SF. Early-phase enrichment of chemotaxis suggests that targeting chemokines may offer therapeutic potential for early disease remission.