Synovial Fluid Immune Cell Landscape in Juvenile Idiopathic Arthritis

ABSTRACT Juvenile idiopathic arthritis (JIA) is a common inflammatory rheumatic disease of childhood, yet the mechanisms driving immune activation in affected joints remain unclear. In this study, we analyzed synovial fluid (SF) immune cells from patients with JIA using two complementary methodologies, single‐cell multiomics and flow cytometry. SF displayed a markedly altered immune landscape compared with blood. Both myeloid and plasmacytoid dendritic cells were enriched in SF, and SF monocytes exhibited signs of macrophage differentiation. B cells were strikingly rare in SF, and the few B cells present were predominantly CD21 lo age‐associated B cells. In contrast, CD56 hi CD16 − NK cells and CD161 − γδ T cells were strongly enriched in SF. Among SF CD4 + T cells, regulatory T cells, T peripheral helper cells, and CD161 + T cells were most abundant, while CD8 + T cells exhibited a tissue‐resident memory phenotype with a broad expression of different granzymes. Immune cell frequencies in SF correlated poorly with matched blood samples, and no clear association between SF immune cell composition and JIA subtype or selected clinical parameters was detected. This comprehensive characterization of the SF immune environment provides a foundation for future studies aimed at defining the roles of specific immune cell subsets in JIA pathogenesis.