巨噬细胞集落刺激因子与脊柱关节病发病机制相关性的初步探讨

The study of macrophage colony-stimulating factor in the pathogenesis of spondyloarthropathy

目的通过检测脊柱关节病(SpA)患者血清和关节液中巨噬细胞集落刺激因子(M-CSF)的表达及其与SpA患者疾病活动的相关性来探讨M-CSF在SpA发病机制中的作用。方法用含有1 176个基因点阵的寡核苷酸基因芯片技术检测了11例SpA患者的滑膜组织和10名正常对照的外周血单个核细胞(PBMC)的基因表达谱。同时应用酶联免疫吸附试验(ELISA)检测了两组强直性脊柱炎(AS)患者血清中M-CSF的表达水平,一组是41例未用任何抗肿瘤坏死因子(TNF)-α等生物制剂治疗的AS患者血清,另一组是13例应用TNF-α抑制剂infliximab治疗前和治疗14周后的AS患者血清,同时检测了28名正常对照个体血清和15例SpA患者关节液中M-CSF的水平。结果关节液和外周血清中均可检测出M-CSF；41例未用任何生物制剂治疗的AS患者,其血清M-CSF的水平与AS疾病活动指数(BASDAI)具有明显相关性(r=0．41,P=0．004)；应用infliximab治疗14周后,AS患者BASDAI值比治疗前显著下降(P=0．000 07),但是M-CSF值下降不明显。结论M-CSF是研究SpA发病机制的一个肯定和有用的候选基因,其调节SpA的信号途径与TNF-α的作用途径不同,这有可能为开发新的治疗SpA的生物抑制剂提供理论基础。

Objective To study the macrophage colony-stimulating factor （M-CSF） expression levels of serum and synovial fluids from patients with spondyloarthropathy （SPA） and its contribution to the pathogenesis of SpA. Methods Eleven SpA synovial tissue samples were compared to those from peripheral blood mononuclear cells （PBMC） of 10 normal subjects using a 1176 gene array. M-CSF was detected in both serum samples and synovial fluids by enzyme linked immunosorbent assay （ELISA）. Two groups of AS subjects were tested. The first group consisted of 41 ankylosing spondylitis （AS） patients who had not been treatd with biologics. The second group consisted of 13 subjects whose 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 15 SpA patients. Results Expression of M-CSF could be detected in both serum samples and synovial fluids. The concentration of M-CSF in the group of 41 AS patients not treated with biologics correlated with the Bath Ankylosing Spondylitis Disease Activity Index （BASDAI） values （r=0.41, P=0.004）. Treatment of infliximab in AS patients led to a significant decrease in the values of BASDAI （P=0.000 07）, but no significant change in the serum M-CSF values. Conclusion M-CSF is a promising candidate for research on the mechanisms of SpA and its signaling on pathway in SpA is different from tumor necrosis factor （TNF）-α, and it may provide new basis for developing new anti-biologics for SpA.