Therapeutic effects of a novel BAFF blocker on arthritis

Bailing Zhou,Li Yang,Qibing Xie,Gu He,Yi Luo,Xiaoqing Su,Hailong Zhang,Chaoheng Yu,Xuyang Xia,Xiaopeng Li

doi:10.1038/s41392-019-0051-z

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-κB activation. Thus, BAFF-Trap may be a valuable agent for the effective treatment of RA.

Highlights

Rheumatoid arthritis (RA) is a systemic autoimmune disease, which is related to activated T cells and macrophages, and involved in activated B cells.[1,2] B-cell-depleting therapy can improve the symptoms of RA patients.[3,4]B-cell activating factor (BAFF) is a member of the TNF superfamily expressed by macrophages, monocytes, dendritic cells (DCs), stimulated neutrophils, and stromal cells.[5]
The results showed that there were obvious bone anti-collagen type II (CII) IgG, and mice treated with BAFF-Trap had reduced levels destruction, cysts and joint effusion in phosphate-buffered saline (PBS) group and hIgG group, of CII-specific IgG1, IgG2a, and IgG2b antibodies than control whereas BAFF-Trap could repair damaged bone and eliminate mice (Fig. 4d, e)
BAFF has an important role in the generation and development of RA and collagen-induced arthritis (CIA)

Summary

INTRODUCTION

Rheumatoid arthritis (RA) is a systemic autoimmune disease, which is related to activated T cells and macrophages, and involved in activated B cells.[1,2] B-cell-depleting therapy can improve the symptoms of RA patients.[3,4]. BAFF-Trap shows no side effects and effectively inhibits arthritis development and joint destruction in collagen-induced arthritis (CIA) mice and adjuvantinduced arthritis (AIA) rats, which are associated with regulating disease-related immune cells and inhibiting the generation of proinflammatory cytokine

MATERIALS AND METHODS

Findings

DISCUSSION