Faculty of Medicine, University of Nis, 18000 Nis, Serbia.
Institute for Treatment and Rehabilitation "Niska Banja", 18205 Niska Banja, Serbia.
Medicina (Kaunas). 2023 Jan 14;59(1):167. doi: 10.3390/medicina59010167.
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.
基质金属蛋白酶（MMPs）是软骨和关节损伤发病机制中的关键酶，也是类风湿关节炎（RA）早期侵蚀性形式的潜在新型生物标志物。首先，本研究旨在比较 RA 和骨关节炎（OA）患者血浆（PL）和滑液（SF）中 MMP-9 的水平。其次，目的是研究 SF 和 PL 中 MMP-9 水平与 RA 的早期侵蚀性变化之间的关联，并最终确定 MMP-9 水平与疾病的血清学参数（类风湿因子-RF 和抗瓜氨酸蛋白抗体-ACPA）之间的关联。材料和方法：本研究共纳入 156 名受试者（84 名 RA 患者和 72 名 OA 患者作为对照组）。通过夹心酶联免疫吸附试验（ELISA）法测量所有受试者 PL 和 SF 中的 MMP-9 水平。使用手部和足部的标准 X 光片检测关节损伤，并将其分类为侵蚀性或非侵蚀性 RA。使用 Larsen 评分（LS）对关节损伤进行定量评估，并使用其年度变化（∆LS）评估疾病的放射学进展。结果：与对照组相比，RA 患者的 PL 和 SF 中 MMP-9 水平明显更高（PL：19.26 ± 7.54 比 14.57 ± 3.11 ng/mL，p<0.01；SF：16.17 ± 12.25 比 0.75 ± 0.53 ng/mL，p<0.001），并且在侵蚀性 RA 患者的 SF 中明显高于非侵蚀性 RA 患者（18.43 ± 12.87 比 9.36 ± 7.72，p<0.05）。与非侵蚀性早期 RA 相比，侵蚀性 RA 患者的放射学进展更快（11.14 ± 4.75 比 6.13 ± 2.72，p<0.01）。SF 中 MMP-9 水平，而不是 PL 中 MMP-9 水平，与侵蚀性和非侵蚀性 RA 患者的放射学进展均显著相关（ρ=0.38 和 ρ=0.27）。我们没有发现 RF 与早期 RA 中 MMP-9 水平之间存在显著关联，但 ACPA 水平与 SF 中 MMP-9 水平显著相关（r=0.48）。结论：RA 患者的 PL 和 SF 中 MMP-9 水平明显高于 OA 患者。SF 中 MMP-9 水平在侵蚀性 RA 中明显高于非侵蚀性 RA。它与疾病的放射学进展和抗瓜氨酸蛋白抗体的水平显著相关。
