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Therapeutic effects of a novel BAFF blocker on arthritis.


ABSTRACT: 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-?B activation. Thus, BAFF-Trap may be a valuable agent for the effective treatment of RA.

SUBMITTER: Zhou B 

PROVIDER: S-EPMC6565627 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Therapeutic effects of a novel BAFF blocker on arthritis.

Zhou Bailing B   Zhang Hailong H   Su Xiaoqing X   Luo Yi Y   Li Xiaopeng X   Yu Chaoheng C   Xie Qibing Q   Xia Xuyang X   He Gu G   Yang Li L  

Signal transduction and targeted therapy 20190614


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 s  ...[more]

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