State Key Laboratory of Cancer Biology, Department of Neurology, Xijing Hospital, Fourth Military Medical University, 17 Changle West Road, Shaanxi, Xi'an 710032, China.
State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, 17 Changle West Road, Xi'an 710032, China ; The Biotechnology Center, Fourth Military Medical University, 17 Changle West Road, Xi'an, Shaanxi 710032, China.
Biomed Res Int. 2014;2014:854954. doi: 10.1155/2014/854954. Epub 2014 Mar 25.
B cell activating factor (BAFF) is a cytokine of tumor necrosis factor family mainly produced by monocytes and dendritic cells. BAFF can regulate the proliferation, differentiation, and survival of B lymphocytes by binding with BAFF-R on B cell membrane. Accumulating evidences showed that BAFF played crucial roles and was overexpressed in various autoimmune diseases such as systemic lupus erythematous (SLE) and rheumatoid arthritis (RA). This suggests that BAFF may be a therapeutic target for these diseases. In the present study, we developed a BAFF therapeutic vaccine by coupling a T helper cell epitope AKFVAAWTLKAA (PADRE) to the N terminus of BAFF extracellular domains (PADRE-BAFF) and expressed this fusion protein in Escherichia coli. The purified vaccine can induce high titer of neutralizing BAFF antibodies and ameliorate the syndrome of complete Freund's adjuvant (CFA) induced rheumatoid arthritis in rats. Our data indicated that the BAFF autovaccine may be a useful candidate for the treatment of some autoimmune diseases associated with high level of BAFF.
B 细胞激活因子（BAFF）是肿瘤坏死因子家族的一种细胞因子，主要由单核细胞和树突状细胞产生。BAFF 通过与 B 细胞膜上的 BAFF-R 结合，调节 B 淋巴细胞的增殖、分化和存活。越来越多的证据表明，BAFF 在多种自身免疫性疾病中发挥着关键作用，并过度表达，如系统性红斑狼疮（SLE）和类风湿关节炎（RA）。这表明 BAFF 可能是这些疾病的治疗靶点。在本研究中，我们通过将 T 辅助细胞表位 AKFVAAWTLKAA（PADRE）与 BAFF 细胞外结构域的 N 端连接，开发了一种 BAFF 治疗性疫苗（PADRE-BAFF），并在大肠杆菌中表达了这种融合蛋白。纯化的疫苗可诱导高滴度的中和 BAFF 抗体，并改善完全弗氏佐剂（CFA）诱导的大鼠类风湿关节炎的综合征。我们的数据表明，BAFF 自身疫苗可能是治疗某些与高水平 BAFF 相关的自身免疫性疾病的有用候选药物。
