Diagnostic Value of Interleukin-34 as a Novel Biomarker for Severity of Knee Osteoarthritis.

OBJECTIVES

This study aimed to determine whether plasma and synovial fluid interleukin-34 (IL-34), an inflammatory cytokine reportedly implicated in synovial inflammation-induced joint degeneration, were associated with radiographic severity of knee osteoarthritis (OA) patients and could emerge as knee OA biomarkers.

DESIGN

Ninety-six knee OA patients and 72 healthy controls were recruited. Plasma and synovial fluid IL-34 levels were quantified using ELISA. IL-34 mRNA and protein expressions in inflamed ( = 15) and noninflamed synovial tissues ( = 15) of knee OA patients were determined using real-time polymerase chain reaction and immunohistochemistry, respectively.

RESULTS

Significant increases in plasma and synovial fluid IL-34 levels were found in knee OA patients-especially those with advanced stage ( < 0.001, < 0.001, respectively). Both plasma and synovial fluid IL-34 levels were positively associated with radiographic severity ( = 0.64, < 0.001; = 0.50, < 0.001, respectively). There was a direct link between plasma and synovial fluid IL-34 ( = 0.64, < 0.001). Receiver operating characteristic curve analysis uncovered that the optimal cutoff value of plasma IL-34 as a novel biomarker reflecting knee OA severity was defined at 3750.0 pg/mL (AUC = 0.85), with a sensitivity of 83.1% and a specificity of 74.2%. Further analysis revealed that mRNA expression was significantly upregulated in inflamed synovium compared with noninflamed synovium obtained from knee OA patients ( < 0.001), consistent with protein expression analysis demonstrating IL-34 overexpression localized in the lining and sublining layers of inflamed synovium.

CONCLUSIONS

All findings suggest that elevated plasma and synovial fluid IL-34 would reflect knee OA severity and might have potential utility as biomarkers for the disease progression.