Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Lupus. 2010 Nov;19(13):1534-49. doi: 10.1177/0961203310375268.
B-cell activating factor belonging to tumour necrosis factor family (BAFF) is essential for B-cell survival and function through interaction with its receptors BAFF receptor 3 (BR3), B-cell maturation antigen (BCMA) and/or transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), though BCMA and/or TACI can also bind to a proliferation-inducing ligand (APRIL). We evaluate the correlation of the expressions of these ligands/receptors with different clinical manifestations of systemic lupus erythematosus (SLE). Levels of BAFF and APRIL in plasma from 73 SLE patients were determined by enzyme-linked immunosorbent assay. Expressions of BR3, TACI and BCMA on CD19+ B cells were detected by flow cytometry. Clinical data were collected and disease activity was evaluated using SLEDAI-2000. SLE patients had elevated BAFF and APRIL levels in their plasma. BAFF levels correlated positively with SLEDAI while negatively with the BR3 protein expression on CD19+ B cells (p < .05). The detected BR3 protein expression in SLE patients was reduced on CD19+IgD+CD27-, CD19+IgD+CD27+ as well as CD19+IgD-CD27+ B cells compared to the counterparts of healthy controls (p < .001), whereas SLE patients did not differ from healthy controls in BR3 mRNA levels. In untreated new-onset patients, the expression rate of BR3 on CD19+ B cells correlated negatively with SLEDAI (p < .05). Elevation of BAFF and reduction of BR3 on CD19+ B cells were more obvious in those with lupus nephritis (LN, p < .05). TACI expression on CD19+ B cells was up-regulated only in those subjects with LN (p < .05). Elevated plasma BAFF and reduced BR3 protein expression on peripheral B cells could act as biomarkers for active disease in SLE patients. High expression of TACI may indicate the occurrence of LN.
B 细胞激活因子属于肿瘤坏死因子家族(BAFF),通过与其受体 BAFF 受体 3(BR3)、B 细胞成熟抗原(BCMA)和/或跨膜激活剂和钙调节剂及 cyclophilin 配体相互作用因子(TACI)相互作用,对 B 细胞的存活和功能至关重要,尽管 BCMA 和/或 TACI 也可以与增殖诱导配体(APRIL)结合。我们评估了这些配体/受体的表达与系统性红斑狼疮(SLE)不同临床表现之间的相关性。通过酶联免疫吸附试验测定 73 例 SLE 患者血浆中的 BAFF 和 APRIL 水平。通过流式细胞术检测 CD19+B 细胞上 BR3、TACI 和 BCMA 的表达。收集临床资料并采用 SLEDAI-2000 评估疾病活动度。SLE 患者血浆中 BAFF 和 APRIL 水平升高。BAFF 水平与 SLEDAI 呈正相关,与 CD19+B 细胞上 BR3 蛋白表达呈负相关(p<0.05)。与健康对照组相比,SLE 患者 CD19+IgD+CD27-、CD19+IgD+CD27+和 CD19+IgD-CD27+B 细胞上检测到的 BR3 蛋白表达减少(p<0.001),而 BR3mRNA 水平在 SLE 患者与健康对照组之间无差异。在未经治疗的新发患者中,CD19+B 细胞上 BR3 的表达率与 SLEDAI 呈负相关(p<0.05)。狼疮肾炎(LN)患者 BAFF 升高和 CD19+B 细胞上 BR3 减少更为明显(p<0.05)。仅在 LN 患者中 CD19+B 细胞上 TACI 表达上调(p<0.05)。SLE 患者外周血 B 细胞中 BAFF 升高和 BR3 蛋白表达减少可作为疾病活动的生物标志物。TACI 高表达可能提示发生 LN。