Matrix Metalloproteinase-9 Level in Synovial Fluid-Association with Joint Destruction in Early Rheumatoid Arthritis.

Abstract

Background and objective: Matrix metalloproteinases (MMPs) are the key enzymes in the pathogenesis of cartilage and joint damage and potentially a new biomarker of the early erosive form of rheumatoid arthritis (RA). Firstly, the study aimed to compare the level of MMP-9 in plasma (PL) and synovial fluid (SF) of patients with RA and osteoarthritis (OA). Secondly, the goal was to examine the association of MMP-9 level in PL and SF with early erosive changes in RA, and finally, to determine the association of MMP-9 level with serological parameters of the disease (rheumatoid factor-RF and anti-citrulline protein antibodies-ACPA). Materials and Methods: A total of 156 subjects were involved in this study (84 patients with RA and 72 patients with OA, who were involved as a control group). MMP-9 level was measured in PL and SF of all subjects by the sandwich enzyme-linked immunosorbent assay (ELISA) method. Standard radiographs of the hands and feet were used to detect joint damage and classification into erosive or non-erosive RA. The Larsen score (LS) was used for the quantitative assessment of joint damage, and its annual change (∆ LS) was used to assess the radiographic progression of the disease. Results: MMP-9 level in PL and SF was significantly higher in RA compared to controls (PL: 19.26 ± 7.54 vs. 14.57 ± 3.11 ng/mL, p< 0.01; SF: 16.17 ± 12.25 vs. 0.75 ± 0.53 ng/mL, p < 0.001) as well as in SF of patients with erosive compared to non-erosive RA (18.43 ± 12.87 vs. 9.36 ± 7.72; p < 0.05). Faster radiographic progression was recorded in erosive compared to non-erosive early RA (11.14 ± 4.75 vs. 6.13 ± 2.72; p < 0.01). MMP-9 level in SF, but not in PL, significantly correlates with the radiographic progression in both erosive and non-erosive RA (ρ = 0.38 and ρ = 0.27). We did not find a significant association between RF and MMP-9 level in early RA, but the ACPA level significantly correlates with MMP-9 level in SF (r = 0.48). Conclusion: The level of MMP-9 in plasma and synovial fluid of patients with RA is significantly higher compared to patients with osteoarthritis. The level of MMP-9 in synovial fluid is significantly higher in erosive than non-erosive early RA. It is significantly associated with the radiographic progression of the disease and the level of anti-citrulline protein antibodies.