Keyszer G, Lambiri I, Nagel R, Keysser C, Keysser M, Gromnica-Ihle E, Franz J, Burmester G R, Jung K
Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin-Buch, Berlin, Germany.
J Rheumatol. 1999 Feb;26(2):251-8.
To investigate whether plasma levels of matrix metalloproteinases 3 (MMP-3, stromelysin), MMP-1 (collagenase), tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP1/TIMP-1 complex (MT complex) are specifically elevated in erosive joint diseases compared to nonerosive rheumatic diseases, and to assess how these markers reflect the clinical activity of rheumatoid arthritis (RA) compared to circulating cytokines and markers of connective tissue turnover as well as established variables [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor titer].
Plasma levels of MMP-3, MMP-1, TIMP- 1, and MT complex were determined by ELISA. One hundred fifteen patients with RA, 20 with osteoarthritis (OA), 28 with psoriasis arthritis (PsA), 24 with ankylosing spondylitis (AS), 3 groups with systemic autoimmune diseases, and 30 healthy controls were analyzed. In patients with RA routine laboratory variables, circulating inflammatory cytokines [interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-6], collagen degradation products, and markers of bone formation were determined in parallel and were correlated to 4 variables of clinical activity.
MMP-3 levels were markedly elevated in RA compared to controls and OA, but also in all other groups, including 26 patients with systemic lupus erythematosus (SLE). MMP-1 levels were significantly elevated in RA, but also in OA, PsA, SLE, and mixed connective tissue disease. In contrast, MT complex was elevated in RA only. TIMP-1 was not different from controls. CRP levels, MMP-3, and ESR correlated best with clinical activity of RA. In contrast, there was no correlation of IL-1 and TNF-alpha and only a weak correlation of IL-6 with clinical measures. Among variables of connective tissue turnover, only pyridinoline and deoxypyridinoline crosslinks were weakly correlated with disease activity.
Elevated MMP-3 and MMP-1 levels are not specific for RA or for erosive joint diseases in general. In contrast, elevated MT complex levels were observed in patients with RA. However, the correlation of MT-1 with clinical data was weaker than that of MMP-3. Elevated MMP-3 levels reflected disease activity of RA better than cytokine levels or markers of connective tissue turnover. However, MMP-3 levels do not exceed the association of CRP with clinical activity.
研究与非侵蚀性风湿性疾病相比，侵蚀性关节疾病患者血浆中基质金属蛋白酶3（MMP - 3，基质溶解素）、MMP - 1（胶原酶）、金属蛋白酶组织抑制剂1（TIMP - 1）以及MMP1/TIMP - 1复合物（MT复合物）水平是否特异性升高，并评估与循环细胞因子、结缔组织更新标志物以及既定变量[C反应蛋白（CRP）、红细胞沉降率（ESR）和类风湿因子滴度]相比，这些标志物如何反映类风湿关节炎（RA）的临床活动。
采用酶联免疫吸附测定法（ELISA）测定血浆中MMP - 3、MMP - 1、TIMP - 1和MT复合物的水平。分析了115例类风湿关节炎患者、20例骨关节炎（OA）患者、28例银屑病关节炎（PsA）患者、24例强直性脊柱炎（AS）患者、3组系统性自身免疫性疾病患者以及30名健康对照者。对类风湿关节炎患者同时测定常规实验室变量、循环炎症细胞因子[白细胞介素1（IL - 1）、肿瘤坏死因子 - α（TNF - α）和IL - 6]、胶原降解产物以及骨形成标志物，并将其与4项临床活动变量进行相关性分析。
与对照组和骨关节炎患者相比，类风湿关节炎患者的MMP - 3水平显著升高，但在所有其他组中也升高，包括26例系统性红斑狼疮（SLE）患者。MMP - 1水平在类风湿关节炎患者中显著升高，但在骨关节炎、银屑病关节炎、系统性红斑狼疮和混合性结缔组织病患者中也升高。相比之下，MT复合物仅在类风湿关节炎患者中升高。TIMP - 1水平与对照组无差异。CRP水平、MMP - 3和ESR与类风湿关节炎的临床活动相关性最佳。相比之下，IL - 1和TNF - α与临床指标无相关性，IL - 6与临床指标仅有微弱相关性。在结缔组织更新变量中，只有吡啶啉和脱氧吡啶啉交联与疾病活动有微弱相关性。
MMP - 3和MMP - 1水平升高并非类风湿关节炎或一般侵蚀性关节疾病所特有。相比之下，在类风湿关节炎患者中观察到MT复合物水平升高。然而，MT - 1与临床数据的相关性弱于MMP - 3。MMP - 3水平升高比细胞因子水平或结缔组织更新标志物更能反映类风湿关节炎的疾病活动。然而，MMP - 3水平与临床活动的相关性不及CRP。
