Reseach for the mechanism of over-expression of soluble CD40-ligand and regulating drugs.

检测系统性红斑狼疮(SLE)、类风湿关节炎(RA)和类风湿血管炎(RV)患者血浆中可溶性CD40配体(SCD154)水平，探讨sCD154水平与临床变量的关系。对39例RA患者(其中9例同时诊断为RV)的血浆sCD154水平进行了定量检测，并与20例健康人进行了比较。建立了针对sCD154的双抗体夹心ELISA法，并用同型相合的免疫球蛋白Ig G和预吸附法检测了其特异性。同时测定患者血清中类风湿因子(Ig M-RF、Ig G-RF)的滴度，并测定其他实验室指标。RA患者血浆sCD154水平高于正常人(p&lt；0.02)。与无血管炎的RA患者相比，RV患者的血浆sCD154水平显著升高(p&lt；0.001)。对照酶联免疫吸附试验和对sCD154的吸收试验表明，本系统可用于RA患者血浆sCD154的检测。RA患者血浆sCD154水平与Ig M-RF和Ig G-RF滴度均呈显著正相关(r分别为0.001.6 4和0.61，P均<0.0 1)，RV患者治疗后sCD15 4水平下降。综上所述，我们发现RA患者血浆中存在sCD154，在血管炎患者中水平尤其高。SCD154与RF滴度的相关性提示CD154-CD40通路可能与致病RF的产生有关。

Specific aim of this project is to determine the levels of soluble CD40-ligand (sCD154) in the plasma of patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and rheumatoid vasculitis (RV), and to examine the relationship between the levels of sCD154 in plasma and the clinical variables. The levels of sCD154 were quantified in 39 plasma samples from patients with RA, including 9 patients who were also diagnosed with RV, and compared with those of 20 healthy subjects. Sandwich ELISA specific for sCD154 was established and specificity of the ELISA was tested by control ELISA using isotype-matched IgG and preabsorption assay. The titers of IgM and IgG rheumatoid factor (IgM-RF, IgG-RF) for each patient were determined simultaneously, and values of other laboratory variables were also determined. Levels of sCD154 inplasma were higher in patients with RA than in the healthy subjects (p < 0.02). Compared with RA patients without vasculitis, patients with RV had significantly higher levels of sCD154 in their plasma (p < 0.001). Control ELISA and absorption assay of sCD154 indicated that our ELISA system was capable of measuring plasma sCD154 in RA patients. Levels of sCD154 in RA plasma correlated significantly with both of IgM-RF and IgG-RF titers (r = 0.64 and 0.61, respectively, both p < 0.001), The levels of sCD154 decreased after commencement of treatment for vasculitis in cases with RV. In conclusion, we identified the presence of sCD154 in RA plasma, with especially high levels in cases with vasculitis. Correlation between sCD154 and RF titers indicates the CD154-CD40 pathway is likely related to pathogenic RF production.