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

Abstract

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 (n = 15) and noninflamed synovial tissues (n = 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 (P < 0.001, P < 0.001, respectively). Both plasma and synovial fluid IL-34 levels were positively associated with radiographic severity (r = 0.64, P < 0.001; r = 0.50, P < 0.001, respectively). There was a direct link between plasma and synovial fluid IL-34 (r = 0.64, P < 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 IL-34 mRNA expression was significantly upregulated in inflamed synovium compared with noninflamed synovium obtained from knee OA patients (P < 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.