Abnormal B cells, which produce antibodies against self-antigens, play a key role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). B-cell activating factor (BAFF) is closely associated with abnormal B cells and participates in B cell-mediated autoimmune diseases; thus, neutralizing BAFF is an effective method for treating these diseases. Our group designed a novel fusion protein, BAFF-Trap, that contains the BAFF-binding domains of two BAFF receptors (TACI and BAFF-R) and the Fc domain of human IgG1. In this study, we showed that BAFF-Trap significantly decreased the autoantibody levels, BAFF concentrations and B cells numbers in MRL/lpr mice. BAFF-Trap suppressed the expression of pro-inflammatory cytokines in the kidney and decreased the frequencies of T cell subsets and dendritic cells. Furthermore, BAFF-Trap reduced proteinuria and IgG deposition, relieved glomerular damage in the kidney, and markedly improved the survival rate of mice. These results indicated that BAFF-Trap may be a potential drug for the treatment of SLE.

产生针对自身抗原的抗体的异常B细胞在自身免疫疾病（例如系统性红斑狼疮（SLE）和类风湿性关节炎（RA））的发病机理中起关键作用。B细胞活化因子（BAFF）与异常B细胞密切相关，并参与B细胞介导的自身免疫性疾病；因此，中和BAFF是治疗这些疾病的有效方法。我们的小组设计了一种新型融合蛋白BAFF-Trap，它包含两个BAFF受体（TACI和BAFF-R）的BAFF结合域和人IgG1的Fc域。在这项研究中，我们表明BAFF-Trap显着降低了MRL / lpr小鼠的自身抗体水平，BAFF浓度和B细胞数量。BAFF-Trap抑制肾脏中促炎性细胞因子的表达，并降低T细胞亚群和树突状细胞的频率。此外，BAFF-Trap可以减少蛋白尿和IgG沉积，减轻肾脏中的肾小球损害，并显着提高小鼠的存活率。这些结果表明BAFF-Trap可能是治疗SLE的潜在药物。