The soluble CD40 ligand sCD154 in systemic lupus erythematosus
The soluble CD40 ligand sCD154 in systemic lupus erythematosus
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DOI：
10.1172/jci7014
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发表时间：
1999-10-01
影响因子：
15.9
通讯作者：
Kipps, TJ
中科院分区：
文献类型：
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作者：
Kato, K;Santana-Sahagún, E;Kipps, TJ
我们发现，活动期系统性红斑狼疮(SLE)患者的血浆可诱导人B细胞系(RAMOS)表达活动期SLE患者外周血B细胞上常见的高水平免疫辅助分子。SLE血浆诱导这种表型改变的能力可以被针对CD40配体(CD154)的中和抗体所消除，但不能被抗肿瘤坏死因子-a的抗体所消除。抗CD154免疫沉淀法在活动期SLE患者血浆中检测到一种20 kDa的蛋白，而在正常人血浆中未检测到这种蛋白，表明这种血浆中含有可溶性CD154(SCD154)。采用定量ELISA法，我们发现活动期疾病患者的血浆中sCD154水平显著高于正常献血者。SLE患者血淋巴细胞CD154转录本水平与血浆中sCD154相对浓度呈正相关。此外，血浆sCD154水平与抗双链DNA自身抗体滴度及临床疾病活动性相关。这些研究表明，SLE患者中的sCD154可能是与SLE疾病活动性相关的CD40的功能配体。
We found that the plasma of patients with active systemic lupus erythematosus (SLE) could induce a human B-cell line (Ramos) to express high levels of immune accessory molecules that are commonly found on blood B cells of patients with active SLE. The ability of SLE plasma to induce such phenotypic changes could be abrogated by neutralizing antibodies specific for the CD40 ligand (CD154) but not by antibodies to TNF-a. Immunoprecipitation studies with anti-CD154 identified a 20-kDa protein in the plasma of SLE patients with active disease, but not in plasma of normal donors, indicating that such plasma contained soluble CD154 (sCD154). Using a quantitative ELISA method, we found that the plasma of patients with active disease had levels of sCD154 that were significantly higher than those found in plasma of normal donors. Levels of CD 154 transcripts in SLE blood lymphocytes correlated with the relative concentrations of sCD154 found in SLE plasma. Furthermore, plasma levels of sCD154 correlated with the titers of anti-double-stranded DNA autoantibody and with clinical disease activity. These studies indicate that sCD154 of patients with SLE may act as a functional ligand for CD40 that is associated with SLE disease activity.