The lack of disease-modifying treatments for osteoarthritis (OA) is linked to a shortage of suitable biomarkers. This study combines multi-molecule synovial fluid analysis with machine learning to produce an accurate diagnostic biomarker model for end-stage knee OA (esOA). Synovial fluid (SF) from patients with esOA, non-OA knee injury, and inflammatory knee arthritis were analyzed for 35 potential markers using immunoassays. Partial least square discriminant analysis (PLS-DA) was used to derive a biomarker model for cohort classification. The ability of the biomarker model to diagnose esOA was validated by identical wide-spectrum SF analysis of a test cohort of ten patients with esOA.Aims
Methods
Inflammatory changes in synovial tissues occur commonly in knee osteoarthritis (OA) and are termed “inflammatory OA”. The pathogenic significance of this inflammatory OA is uncertain. It is also not known whether inflammatory changes in the synovial membrane are reflected in the synovial fluid (SF) and whether the SF contains a similar inflammatory cell infiltrate. This study examined 34 cases of knee joint OA and cytologically and immunohistochemically characterised inflammatory cells in the synovial membrane and SF. Specimens of SF and synovial membrane were taken at the time of knee arthroplasty. All cases of inflammatory OA synovium contained (CD68+) macrophages; several cases also contained a scattered, focally heavy (CD3+) lymphocytic infiltrate and occasional lymphoid aggregates. Inflammatory changes in OA SF reflected this cell composition with numerous CD68+ macrophages and CD3+ lymphocytes being noted in inflammatory OA cases. The SF volume was greater (>
5ml) in cases of inflammatory OA. Non-inflammatory OA knee joints contained very few inflammatory cells, which were mainly macrophages, in both the synovial membrane and SF. Our findings indicate that inflammatory changes in the synovial membrane of OA knee joints are reflected in the SF and that the volume of SF is commonly increased in cases of inflammatory OA. Both macrophages and lymphocytes in the inflammatory infiltrate of knee joint SF may contribute to joint destruction in OA by providing mononuclear phagocyte osteoclast precursors and the production of inflammatory cytokines and growth factors that promote osteoclastogenesis. In conclusion, the cytology of SF and synovitic membrane are similar in inflammatory OA. With knee effusions of greater than 5mls and inflammatory synovitic membrane consideration of total knee arthoplasty in the presence of single compartment disease should be considered because of the risk of further joint destruction.
