REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1538555
This article is part of the Research TopicThe pathogenesis and novel treatment options in AIBDsView all 3 articles
The role of B cell-activating factor System in Autoimmune Diseases: Mechanisms, Disease Implications, and Therapeutic Advances
Provisionally accepted
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
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The B cell-activating factor (BAFF) system, comprising two ligands and three receptors, plays a pivotal role in adaptive and innate immunity, driving autoimmunity through dysregulated B and T cell survival, differentiation, and cytokine production. This review synthesizes evidence linking BAFF system overexpression to multiple autoimmune diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), bullous pemphigoid (BP), pemphigus vulgaris (PV), and alopecia areata (AA), where elevated BAFF system molecule levels correlate with autoantibody titers, disease activity, and post-B cell depletion relapse. BAFF-targeted therapies have demonstrated efficacy in reducing disease activity in SLE and SS. Key challenges include interspecies receptor expression discrepancies and context-dependent signalling cascades. Emerging strategies, such as sequential therapy with rituximab followed by belimumab, show promise in treating refractory autoimmune diseases such as BP and PV by counteracting the post-depletion BAFF surge. Despite progress, mechanistic gaps in BAFF-mediated crosstalk between innate and adaptive immunity, as well as interspecies-specific pathogenesis warrant further investigation using humanized disease models and single-cell transcriptomic profiling. This review underscores the therapeutic potential of BAFF system modulation while advocating for disease-specific clinical trials to optimize precision-therapeutic targeting in autoimmune diseases.
Keywords: B cell-activating factor, Autoimmune Diseases, targeted therapies, Autoimmunity, B cells, T cells
Received: 03 Dec 2024; Accepted: 21 May 2025.
Copyright: © 2025 Li, Shen, Shao, Dang, Wang, Fang and Qiao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Gang Wang, Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
Hui Fang, Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
Hongjiang Qiao, Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
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