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A novel BAFF antagonist, BAFF-Trap, effectively alleviates the disease progression of systemic lupus erythematosus in MRL/lpr mice
Molecular Immunology ( IF 3.2 ) Pub Date : 2020-11-27 , DOI: 10.1016/j.molimm.2020.11.010
Chaoheng Yu , Shuang Chen , Bailing Zhou , Hailong Zhang , Xiaoqing Su , Yi Luo , Li Yang

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.



中文翻译:

新型BAFF拮抗剂BAFF-Trap可有效缓解MRL / lpr小鼠系统性红斑狼疮的疾病进展

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。

更新日期:2020-12-01
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