Inflammation-profiling reveals activated pathways and biomarkers with predictive potential in oligoarticular JIA

Objective We set out to profile the immune mechanisms active in treatment-naïve oligoarticular JIA (oJIA) to improve understanding of its immunopathogenesis, to identify potential biomarkers that can aid diagnosis, predictions and correlate with clinical disease parameters. Methods Using Olink proteomics (Inflammation Panel), we defined and compared the inflammation profiles of 38 plasma and 62 synovial fluid (SF) oJIA samples, 38 plasma samples from healthy age- and sex-matched controls (HC), 12 SF samples from non-arthritic controls and 26 SF samples from knee injury patients. Clinical data were retrieved from the Swedish Pediatric Rheumatology Quality Register. Results Plasma profiles of oJIA and HC were largely overlapping, with IL6 and MMP-1 upregulated in oJIA. In SF, 48 differentially expressed proteins (DEPs) were identified in oJIA, highlighting immune pathways like leukocyte migration, cell chemotaxis and adaptive immunity. Comparative analysis revealed 13 proteins specific to oJIA. Correlations were found between DEPs in oJIA SF and clinical parameters (cJADAS-71, pain, health impact score). Plasma IL6 and MMP-1 showed strong correlation with disease activity and pain, respectively. CXCL9, CXCL10 and CXCL11 were identified as potential predictive biomarkers for disease progression. Conclusions The overlap in plasma inflammation profiles of oJIA and HCs suggests local rather than systemic inflammation in oJIA, underlining the need for synovial fluid-based immunopathogenesis studies. Adaptive immune signatures in oJIA SF distinguished it from knee injury patients, offering potential for diagnostic application. Increased CXCL9, CXCL10 and CXCL11 in SF were associated with chronic disease progression and could serve as prognostic biomarkers and early treatment targets.