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

本项目的具体目的是测定系统性红斑狼疮（SLE）、类风湿性关节炎（RA）和类风湿性血管炎（RV）患者血浆中可溶性cd40 -配体（sCD154）的水平，并探讨血浆中sCD154水平与临床变量的关系。对39例RA患者（包括9例同时诊断为RV的患者）的血浆样本中sCD154的水平进行了量化，并与20名健康受试者的血浆样本进行了比较。建立sCD154特异性夹心ELISA试剂盒，采用同型匹配IgG和预吸收法对照ELISA检测ELISA的特异性。同时测定每位患者的IgM、IgG类风湿因子（IgM- rf、IgG- rf）滴度，并测定其他实验室变量的值。RA患者血浆中sCD154水平高于健康人（p < 0.02）。与无血管炎的RA患者相比，RV患者血浆中sCD154水平显著升高（p < 0.001）。对照ELISA和sCD154的吸收试验表明，我们的ELISA系统能够检测RA患者血浆sCD154。RA血浆中sCD154水平与IgM-RF和IgG-RF滴度均显著相关（r分别为0.64和0.61，p均< 0.001），RV患者在开始血管炎治疗后sCD154水平下降。总之，我们确定了RA血浆中sCD154的存在，在血管炎患者中sCD154的水平特别高。sCD154和RF滴度之间的相关性表明CD154-CD40途径可能与致病性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.