基质金属蛋白酶-3与强直性脊柱炎疾病活动相关性研究

目的本试验拟通过检测强直性脊柱炎(AS)患者血清和关节液中基质金属蛋白酶(MMP)-3的表达水平及分析其与AS病人疾病活动的相关性来确证和探讨MMP-3在AS发病中的作用。方法应用酶联免疫吸附试验(ELISA)检测两组AS患者血清中MMP-3的表达水平,一组是41例未用任何抗肿瘤坏死因子(TNF)-琢等生物制剂治疗的AS患者血清,另一组是13例应用抗TNF-琢单克隆抗体Infliximab治疗前和治疗14周后的AS患者血清,同时对比检测了28名正常对照个体血清和8例AS患者关节液中MMP-3的水平。结果AS患者关节液中MMP-3水平显著高于AS患者外周血水平(P<0.00001);41例未用任何生物制剂治疗的AS患者,其血清MMP-3的水平与AS疾病活动指数(BASDAI)(r=0.48,P=0.0007)和血沉(ESR)(r=0.54,P=0.0001)具有明显相关性;同时应用对数相关分析发现根据BASDAI值判别的病情活动度与ESR(P=0.025)和MMP-3(P=0.04)水平之间亦具有高度相关性。应用Infliximab治疗14周后,AS患者血清MMP-3水平和BASDAI值比治疗前显著下降(P=0.013和P=0.00007)。结论AS患者血清中MMP-3水平可作为评价AS疾病活动性潜在的生物学标志物。此外,由于MMP-3在关节和外周血中均有稳定水平的表达,因此MMP-3还是研究AS发病机制的肯定和有用候选基因。

Serum metalloproteinase-3 correlates with disease activitv in ankylosing spondylitis

Objective To assess metalloproteinase-3 (MMP-3) by microarray techniques to explore if there is significanct correlation between serum level of MMP-3 and disease activity index of ankylosing spondylitis (AS). Methods Serum and synovial fluid level of MMP-3 were measured by ELISA. Two groups of AS subjects were tested. The first group consisted of patients who have not been treated with biological agents. In the second group, serum samples were collected before and 14 weeks after initiation of infliximab. These were compared to serum samples from 28 normal subjects and synovial fluid samples from 8 AS patients. Results While MMP-3 was detectable in serum samples, MMP-3 was especially higher in synovial fluids compared to serum (P<0.000 01). In the group of AS patients not treated with biological agents, MMP-3 correlated with the Bath ankylosing spondylitis disease activity index (BASDAI) values and ESR. Logistic regression analysis showed that MMP-3 value was high in those with severely active disease. Infusions of infliximab in AS patients led to a significant decrease in the value of the BASDAI as well as the serum MMP-3. Conclusion MMP-3 is one of the markers of AS disease activity, and also a promising candidate for research on the pathogenesis of AS.