Synovial Fluid Proteomic Signatures in Different Subtypes of Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) encompasses distinct inflammatory subtypes such as polyarticular (pJIA), oligoarticular (oJIA), systemic onset (sJIA) and enthesitis‐related arthritis (ERA). The molecular mechanisms underlying these subtypes remain unclear. This study aimed to investigate the differential protein expression in synovial fluid (SF) across these subtypes of JIA using high‐throughput proteomics to identify potential diagnostic biomarkers. SF samples were collected from 48 children (45 JIA and 3 non‐inflammatory controls). Samples underwent protein extraction, iTRAQ labelling and LC–MS/MS analysis. A total of 282 proteins were identified. Differentially expressed proteins were analysed using fold change (FC) relative to control samples within each iTRAQ set. Principal component analysis (PCA), gene ontology (GO) and KEGG pathway enrichment analyses were performed to assess the biological significance of the identified proteins. Proteins showing > 5FC were prioritised for clustering and biomarker identification. Distinct proteomic signatures were observed across the studied JIA subtypes. PCA revealed the heterogeneity of protein expression in different subtypes of JIA. S‐100, Septin‐7, MMP‐16 proteins were commonly upregulated in the studied subtypes of JIA except oJIA. Haptoglobin was upregulated in all except sJIA. The specific proteins expressed in various subtypes include pyruvate dehydrogenase phosphate in pJIA, haptoglobin‐related and fibrinogen proteins in ERA, apolipoprotein and Nck‐associated protein in sJIA and leucine‐rich alpha‐2‐glycoprotein in oJIA. GO analysis revealed enrichment in immune‐related biological processes, including complement activation, humoral immune response and antigen binding. The differential SF proteomic signatures observed in the studied JIA subtypes indicate different pathogenic mechanisms in JIA.