A novel BAFF antagonist, BAFF-Trap, effectively alleviates the disease progression of systemic lupus erythematosus in MRL/lpr mice

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.