Wanvisa Udomsinprasert1, Kittaporn Panon1, Siraphop Preechanukul1, Jiraphun Jittikoon1, Artit Jinawath2, Sittisak Honsawek3. 1. Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. 2. Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 3. Department of Biochemistry, Osteoarthritis and Musculoskeleton Research Unit, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
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.
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.
Authors: M Chemel; B Le Goff; R Brion; C Cozic; M Berreur; J Amiaud; G Bougras; S Touchais; F Blanchard; M F Heymann; J M Berthelot; F Verrecchia; D Heymann Journal: Ann Rheum Dis Date: 2011-10-28 Impact factor: 19.103