Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Autoimmunity. 2011 Aug;44(5):357-62. doi: 10.3109/08916934.2010.545846. Epub 2011 Feb 15.
Systemic lupus erythematosus (SLE) is characterized by loss of B cell tolerance and by the presence of polyclonal B cell activation. Syndecan-1 (CD138) is expressed on plasma cells derived from B cells, and is suspected to play a role in SLE. We evaluated the level of soluble CD138 (sCD138) and cell surface expression of CD138 in patients with active SLE, and also examined correlations among the serum levels of BAFF, a proliferation-inducing ligand (APRIL), and CD138 in these patients.
Peripheral blood samples were obtained from 22 SLE patients in an active disease state and 14 normal controls. The levels of serum sCD138, sBAFF, and sAPRIL were measured using ELISA, and cell surface CD138 was analyzed by flow cytometry. The levels of CD138 mRNA were analyzed by RT-PCR. Blood samples were obtained longitudinally when the patients were in an inactive disease state.
The levels of circulating CD138, CD138 mRNA in PBMC, and the numbers of CD20(- )CD38(+)CD138(+) plasma cells were increased in patients with active SLE in comparison with normal controls. Furthermore, the serum sCD138 level in SLE patients was found to correlate with the proportion of CD20(- )CD38(+)CD138(+) plasma cells. On the other hand, patients with active SLE showed a reduced level of sCD138, and this was inversely correlated with the serum level of sAPRIL.
These results suggest that sCD138 may be applicable as a surrogate marker of disease activity, and that syndecan-1/APRIL signaling may be a potential therapeutic target for patients with active SLE.
系统性红斑狼疮(SLE)的特征是 B 细胞耐受丧失和多克隆 B 细胞活化。硫酸乙酰肝素蛋白聚糖-1(CD138)表达于源自 B 细胞的浆细胞上,并且被怀疑在 SLE 中发挥作用。我们评估了处于活动状态的 SLE 患者可溶性 CD138(sCD138)和 CD138 细胞表面表达的水平,还检查了这些患者血清 BAFF、增殖诱导配体(APRIL)和 CD138 水平之间的相关性。
从 22 名处于活动疾病状态的 SLE 患者和 14 名正常对照中获得外周血样本。使用 ELISA 测量血清 sCD138、sBAFF 和 sAPRIL 水平,并通过流式细胞术分析细胞表面 CD138。通过 RT-PCR 分析 CD138 mRNA 水平。当患者处于非活动疾病状态时,纵向采集血液样本。
与正常对照组相比,处于活动状态的 SLE 患者的循环 CD138、PBMC 中的 CD138 mRNA 水平以及 CD20(-)CD38(+)CD138(+)浆细胞的数量均增加。此外,SLE 患者的血清 sCD138 水平与 CD20(-)CD38(+)CD138(+)浆细胞的比例相关。另一方面,处于活动状态的 SLE 患者的 sCD138 水平降低,并且与血清 sAPRIL 水平呈负相关。
这些结果表明,sCD138 可用作疾病活动的替代标志物,并且硫酸乙酰肝素蛋白聚糖-1/APRIL 信号可能是处于活动状态的 SLE 患者的潜在治疗靶点。