Therapeutic effects of a novel BAFF blocker on arthritis

Signal Transduction and Targeted Therapy
Bailing ZhouLi Yang

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.

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Citations

Nov 15, 2020·International Journal of Molecular Sciences·Kathryn M Pflug, Raquel Sitcheran
Jan 16, 2020·Expert Opinion on Therapeutic Targets·Tin KyawAlex Bobik
Feb 9, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniela GiordanoEdward A Clark
Jan 21, 2021·International Journal of Molecular Sciences·Ji Won MinByung Ha Chung
May 20, 2020·Frontiers in Bioengineering and Biotechnology·Weiping LinGang Li
Jul 14, 2020·Frontiers in Immunology·Jessica M Jones, Trine N Jørgensen
Sep 11, 2021·Alimentary Pharmacology & Therapeutics·Albert J Czaja

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Methods Mentioned

BETA
transgenic
electrophoresis
pull-down
flow cytometry
ELISA
PCR
fluorescence activated cell sorting
FACS
ion exchange chromatography
Immunoprecipitation

Software Mentioned

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