A cross-sectional exploratory study of synovial fluid complement levels and ultrasound-assessed structural damage in patients with symptomatic knee osteoarthritis and synovial effusion

Knee osteoarthritis (KOA) is characterised by low-grade inflammation in which the innate immune system, particularly the complement cascade, plays a crucial role. The aim of this study was to evaluate the correlation between synovial fluid (SF) complement levels (C3 and C4) and structural joint damage assessed by ultrasound (US) in patients with KOA. A cross-sectional study was conducted including 31 patients with symptomatic KOA and joint effusion. Ultrasound (US) assessment was performed according to the Outcome Measures in Rheumatology (OMERACT) recommendations, including grading of synovitis, osteophytes, meniscal involvement and cartilage degradation. C3 and C4 levels in SF were measured using turbidimetric techniques. Thirty-one patients with symptomatic KOA were included. In unadjusted analyses, lower SF C3 concentrations were associated with greater lateral osteophyte severity, lateral meniscal extrusion, and lateral cartilage degeneration; however, these associations did not remain statistically significant after FDR correction (adjusted p = 0.090, 0.093, and 0.098, respectively). Exploratory multivariable linear regression suggested an inverse association between lateral osteophyte severity and SF C3 concentrations after adjustment for age, KL grade, CRP, and ESR (B = − 4.510; p = 0.023). Binary logistic regression identified medial osteophyte grade as the only predictor of grade 2 GS-synovitis (OR = 2.60; p = 0.049). Associations between GS-synovitis and medial and lateral osteophyte severity and radiographic severity remained statistically significant after FDR correction (adjusted p = 0.018, 0.047, and 0.033, respectively). Unadjusted analyses suggested inverse associations between SF C3 concentrations and several US measures of structural damage, but these associations did not remain statistically significant after FDR correction. Multivariable analyses suggested associations of lateral osteophyte severity with lower SF C3 concentrations and of medial osteophyte severity with GS-synovitis. Given the exploratory design and limited sample size, these findings are hypothesis-generating and require confirmation in larger cohorts.