B-cell targeted therapy is effective for autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis (RA), although there are setbacks in RA clinical trials. In this study, we designed a novel B-cell activating factor (BAFF) antagonist: BAFF-Trap, a recombinant glycoprotein with BAFF-binding domains of two BAFF receptors (TACI and Br3) linked to Fc domain of human IgG1. Unlike TACI-Fc, BAFF-Trap bound BAFF but not APRIL (a proliferation-inducing ligand), and significantly suppressed the development of collagen-induced arthritis and adjuvant-induced arthritis. Furthermore, BAFF-Trap inhibited proinflammatory cytokine expression, ameliorated joint damage and suppressed B- and T-cell activation. BAFF-Trap reduced dendritic cells in joints, and increased regulatory T cell, regulatory B-cell, and M2 macrophage. The function of BAFF-Trap was related to inhibition of canonical and noncanonical NF-κB activation. Thus, BAFF-Trap may be a valuable agent for the effective treatment of RA.

B细胞靶向治疗对系统性红斑狼疮和类风湿性关节炎（RA）等自身免疫性疾病有效，尽管RA临床试验遇到了挫折。在这项研究中，我们设计了一种新型 B 细胞激活因子 (BAFF) 拮抗剂：BAFF-Trap，这是一种重组糖蛋白，具有与人 IgG1 Fc 结构域连接的两个 BAFF 受体（TACI 和 Br3）的 BAFF 结合结构域。与 TACI-Fc 不同，BAFF-Trap 结合 BAFF，但不结合 APRIL（增殖诱导配体），并显着抑制胶原诱导的关节炎和佐剂诱导的关节炎的发展。此外，BAFF-Trap 还能抑制促炎细胞因子的表达，改善关节损伤并抑制 B 细胞和 T 细胞的激活。BAFF-Trap 减少关节中的树突状细胞，增加调节性 T 细胞、调节性 B 细胞和 M2 巨噬细胞。BAFF-Trap 的功能与抑制经典和非经典 NF-κB 激活有关。因此，BAFF-Trap可能是有效治疗RA的有价值的药物。