Synovial and serum S100A4 expression in rheumatoid arthritis is observed across disease stages and synovial pathotypes

Objectives S100A4 promotes proinflammatory and profibrotic pathways. This study aimed to determine if synovial and serum S100A4 protein levels differ between early rheumatoid arthritis (ERA) and established RA (estRA), and among synovial pathotypes. Methods Synovial biopsies from 14 patients with RA were assessed by immunohistochemistry for S100A4 protein expression, along with markers for T cells, T cell subsets, B cells, plasma cells, macrophages, and dendritic cells. Serum concentrations of S100A4 were measured using an enzyme-linked immunosorbent assay. Synovial tissue was stratified by pathotype (lympho-myeloid, diffuse myeloid, and pauci-immune). Differences in S100A4 protein expression between groups and correlation with disease activity scores (disease activity score 28-erythrocyte sedimentation rate/C-reactive protein [DAS28-ESR/CRP]) were evaluated. Results S100A4 was detected in both synovial tissue and serum. Synovial S100A4 staining intensity did not differ between ERA (n = 5) and estRA (n = 9), or across tissue pathotypes. Serum S100A4 levels were also similar between early and established disease. No significant correlations were found between synovial or serum S100A4 levels and DAS28 components (tender/swollen joint counts, ESR, and CRP). Conclusions In this exploratory study, S100A4 protein expression was consistently detected in RA synovium and serum but did not show clear differences across disease stages or synovial pathotypes, consistent with its proposed proinflammatory and profibrotic roles. These pilot data could support larger-scale study to determine the performance of S100A4 as a biomarker across disease stages and synovial tissue types.