Liang Yongqi, Zha Menglei, Liu Qifeng, Lai Zhifei, Li Lei, Shao Yiming, Sun Jianbo
Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, People's Republic of China.
Dongguan Key Laboratory of Sepsis Translational Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, People's Republic of China.
Drug Des Devel Ther. 2025 Sep 6;19:7837-7852. doi: 10.2147/DDDT.S527687. eCollection 2025.
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial inflammation, joint destruction, and progressive disability. While current therapeutic approaches-including corticosteroids, disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and biologic agents-provide symptomatic relief, their clinical utility remains constrained by substantial limitations such as systemic toxicity, drug resistance, and cumulative adverse effects. These challenges underscore the critical need for novel therapeutic strategies with improved safety and efficacy profiles. The pathogenesis of RA involves multifaceted immune dysregulation, with emerging evidence highlighting the central role of B lymphocytes in both disease initiation and progression. Although B cell-targeted therapies like rituximab demonstrate clinical efficacy, unanswered questions persist regarding the precise immune functions of B cell subpopulations in RA pathogenesis and their potential as translatable therapeutic targets. This comprehensive review examines the clinical burden of RA, limitations of conventional therapies, and the evolving understanding of B cell pathophysiology. We critically evaluate established B cell-directed interventions-including B cell depletion, B cell functional modulation, and regulatory B cell (Breg) promotion-while exploring innovative nanofabrication technologies that may overcome current therapeutic barriers. By synthesizing recent advances in immunomodulatory research, this analysis aims to inform future directions for targeted RA management.
类风湿性关节炎(RA)是一种慢性自身免疫性疾病,其特征为持续性滑膜炎症、关节破坏和进行性残疾。虽然目前的治疗方法——包括皮质类固醇、改善病情抗风湿药(DMARDs)、非甾体抗炎药(NSAIDs)和生物制剂——能提供症状缓解,但其临床效用仍受到诸如全身毒性、耐药性和累积不良反应等重大限制的制约。这些挑战凸显了对具有更高安全性和疗效的新型治疗策略的迫切需求。RA的发病机制涉及多方面的免疫失调,越来越多的证据表明B淋巴细胞在疾病的起始和进展中起着核心作用。尽管像利妥昔单抗这样的B细胞靶向疗法显示出临床疗效,但关于RA发病机制中B细胞亚群的确切免疫功能及其作为可转化治疗靶点的潜力仍存在未解决的问题。这篇综述全面审视了RA的临床负担、传统疗法的局限性以及对B细胞病理生理学的不断演变的认识。我们批判性地评估了既定的B细胞导向干预措施——包括B细胞清除、B细胞功能调节和调节性B细胞(Breg)促进——同时探索可能克服当前治疗障碍的创新纳米制造技术。通过综合免疫调节研究的最新进展,本分析旨在为RA靶向治疗的未来方向提供参考。