Matrix metalloproteinases-3,-8,-9 as markers of disease activity and joint damage progression in early rheumatoid arthritis
Matrix metalloproteinases-3,-8,-9 as markers of disease activity and joint damage progression in early rheumatoid arthritis
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DOI：
10.1136/ard.62.11.1094
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发表时间：
2003-11-01
影响因子：
27.4
通讯作者：
Hanemaaijer, R
中科院分区：
文献类型：
--
作者：
Tchetverikov, I;Lard, LR;Hanemaaijer, R
目的：分析α(2)巨球蛋白(α (2)M)/MMP复合物中MMP-3、-8、-9前基质金属蛋白酶（MMP）活性水平与新发类风湿关节炎（RA）患者关节破坏进展的关系。方法：对109例新近发病的类风湿性关节炎患者进行纵向研究。患者随访2年；临床资料，血液样本和x线片在基线和1年和2年。采用夹心ELISA法和MMP活性测定法测定血清MMPs水平。结果：两年内关节损伤从0到10（中位夏普评分，p < 0.001）。在整个两年中，观察到pro-MMP-3水平稳定，pro-MMP-8和-9以及α M-2/MMP复合物水平显著下降。回归分析显示，发病时血清pro-MMP-3水平与关节损伤进展独立相关（B = 0.7, 95% CI 0.3 ~ 1.1, p = 0.001）。根据关节破坏的速度，将患者分为轻度和重度关节损伤进展患者两组。在任何时候，重度疾病组的前mmp -3水平都明显高于轻度疾病组。两组中前MMP-8和-9水平均下降，而α M-2/MMP复合物水平仅在轻度疾病组中下降。结论：所研究的MMPs血清水平与疾病活动性相关，但疾病发病时血清pro-MMP-3水平也可预测关节损伤进展。
Objective: To analyse the relation between systemic levels of pro-MMP-3, -8, and -9 matrix metalloproteinase (MMP) activity in alpha(2) macroglobulin (alpha(2)M)/MMP complexes and the progression of joint destruction in patients with recent onset rheumatoid arthritis (RA).Methods: 109 patients with RA of recent onset were entered Into this longitudinal study. Patients were followed up for two years; clinical data, blood samples, and radiographs were obtained at baseline and at 1 and 2 years. Serum levels of MMPs were measured by sandwich ELISA and MMP activity assays.Results: During the two years joint damage progressed from 0 to 10 (median Sharp score, p < 0.001). Stable levels of pro-MMP-3 and a significant decrease in the levels of pro-MMP-8 and -9 and alpha M-2/MMP complexes were seen throughout the two years. Regression analysis showed that serum pro-MMP-3 levels at disease onset were independently associated with the progression of joint damage (B = 0.7, 95% CI 0.3 to 1.1, p = 0.001). Based on the rate of joint destruction, patients were divided into two subgroups: patients with mild and severe joint damage progression. The pro-MMP-3 levels were significantly higher in the group with severe compared with mild disease at all times. Levels of pro-MMP-8 and -9 were decreased in both groups, whereas alpha M-2/MMP complex levels decreased in the group with mild disease only.Conclusion: Serum levels of the MMPs studied are associated with disease activity, but serum pro-MMP-3 levels at the onset of disease are also predictive of joint damage progression.