Ichikawa Y, Yamada C, Horiki T, Hoshina Y, Uchiyama M
Department of Internal Medicine 4, Tokai University School of Medicine, Kanagawa, Japan.
Clin Exp Rheumatol. 1998 Sep-Oct;16(5):533-40.
Plasmin and matrix metalloproteinase-3 (MMP-3) have been linked to articular destruction in rheumatoid arthritis (RA). We compared circulating levels of plasmin-mediated fibrin degradation product (FDP D-dimer) and MMP-3 with traditional parameters of disease activity in RA to determine their clinical utility.
Serum levels of MMP-3 and D-dimer were determined by enzyme-linked immunoassays in 60 patients with RA. Twenty healthy females and 21 patients with systemic lupus erythematosus (SLE) served as controls.
MMP-3 (436.8 +/- 474.2 ng/ml) and D-dimer levels (351.2 +/- 296.3 ng/ml) were markedly elevated in the sera from RA patients as compared with healthy controls (43.9 +/- 15.2 ng/ml and 63.0 +/- 64.1 ng/ml, p < 0.0001, respectively). Both levels strongly correlated with each other (r = 0.627, p < 0.0001) and were closely associated with various clinical parameters for the disease activity of RA, including the erythrocyte sedimentation rate (ESR) and the Lansbury's activity index (p < 0.0001). MMP-3 levels were more highly correlated with articular parameters such as the swollen and painful joint counts (r = 0.454, p = 0.0002), whereas D-dimer levels correlated well with C-reactive protein (CRP) levels (r = 0.581, p < 0.0001). In SLE patients, MMP-3 (239.1 +/- 199.6 ng/ml, p < 0.0001) and D-dimer levels (86.9 +/- 85.2 ng/ml, p = 0.0278) were also higher than in healthy controls. Both levels correlated with each other (r = 0.612, p = 0.0025), and were associated with ESR and CRP levels, as was observed in RA patients, but not with most of the other clinical indicators for SLE.
Serum levels of MMP-3 and D-dimer are clinically useful indicators for disease activity in RA. Our results further support the hypothesis that MMP-3 and plasmin may interact in the inflammatory synovial tissues, and thus augment the articular destruction seen in RA. In SLE patients, however, MMP-3 producing cells could be different from in RA patients, and further studies will be required to clarify the pathogenetic mechanism underlying the raised serum levels of MMP-3 and/or D-dimer.
纤溶酶和基质金属蛋白酶-3（MMP-3）与类风湿关节炎（RA）的关节破坏有关。我们比较了纤溶酶介导的纤维蛋白降解产物（FDP D-二聚体）和MMP-3的循环水平与RA疾病活动的传统参数，以确定它们的临床效用。
采用酶联免疫吸附测定法测定60例RA患者血清中MMP-3和D-二聚体水平。20名健康女性和21例系统性红斑狼疮（SLE）患者作为对照。
与健康对照相比，RA患者血清中MMP-3（436.8±474.2 ng/ml）和D-二聚体水平（351.2±296.3 ng/ml）显著升高（分别为43.9±15.2 ng/ml和63.0±64.1 ng/ml，p<0.0001）。两者水平彼此高度相关（r = 0.627，p<0.0001），并与RA疾病活动的各种临床参数密切相关，包括红细胞沉降率（ESR）和兰斯伯里活动指数（p<0.0001）。MMP-3水平与诸如肿胀和疼痛关节计数等关节参数相关性更高（r = 0.454，p = 0.0002），而D-二聚体水平与C反应蛋白（CRP）水平相关性良好（r = 0.581，p<0.0001）。在SLE患者中，MMP-3（239.1±199.6 ng/ml，p<0.0001）和D-二聚体水平（86.9±85.2 ng/ml，p = 0.0278）也高于健康对照。两者水平彼此相关（r = 0.612，p = 0.0025），并且与ESR和CRP水平相关，正如在RA患者中观察到的那样，但与SLE的大多数其他临床指标无关。
血清MMP-3和D-二聚体水平是RA疾病活动的临床有用指标。我们的结果进一步支持了MMP-3和纤溶酶可能在炎症性滑膜组织中相互作用，从而加剧RA中所见关节破坏的假说。然而，在SLE患者中，产生MMP-3的细胞可能与RA患者不同，需要进一步研究以阐明血清MMP-3和/或D-二聚体水平升高的发病机制。
