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Therapeutic effects of a novel BAFF blocker on arthritis

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 wit...

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Autores principales: Zhou, Bailing, Zhang, Hailong, Su, Xiaoqing, Luo, Yi, Li, Xiaopeng, Yu, Chaoheng, Xie, Qibing, Xia, Xuyang, He, Gu, Yang, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565627/
https://www.ncbi.nlm.nih.gov/pubmed/31231554
http://dx.doi.org/10.1038/s41392-019-0051-z
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author Zhou, Bailing
Zhang, Hailong
Su, Xiaoqing
Luo, Yi
Li, Xiaopeng
Yu, Chaoheng
Xie, Qibing
Xia, Xuyang
He, Gu
Yang, Li
author_facet Zhou, Bailing
Zhang, Hailong
Su, Xiaoqing
Luo, Yi
Li, Xiaopeng
Yu, Chaoheng
Xie, Qibing
Xia, Xuyang
He, Gu
Yang, Li
author_sort Zhou, Bailing
collection PubMed
description 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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spelling pubmed-65656272019-06-21 Therapeutic effects of a novel BAFF blocker on arthritis Zhou, Bailing Zhang, Hailong Su, Xiaoqing Luo, Yi Li, Xiaopeng Yu, Chaoheng Xie, Qibing Xia, Xuyang He, Gu Yang, Li Signal Transduct Target Ther Article 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. Nature Publishing Group UK 2019-06-14 /pmc/articles/PMC6565627/ /pubmed/31231554 http://dx.doi.org/10.1038/s41392-019-0051-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhou, Bailing
Zhang, Hailong
Su, Xiaoqing
Luo, Yi
Li, Xiaopeng
Yu, Chaoheng
Xie, Qibing
Xia, Xuyang
He, Gu
Yang, Li
Therapeutic effects of a novel BAFF blocker on arthritis
title Therapeutic effects of a novel BAFF blocker on arthritis
title_full Therapeutic effects of a novel BAFF blocker on arthritis
title_fullStr Therapeutic effects of a novel BAFF blocker on arthritis
title_full_unstemmed Therapeutic effects of a novel BAFF blocker on arthritis
title_short Therapeutic effects of a novel BAFF blocker on arthritis
title_sort therapeutic effects of a novel baff blocker on arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565627/
https://www.ncbi.nlm.nih.gov/pubmed/31231554
http://dx.doi.org/10.1038/s41392-019-0051-z
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