Rheumatoid Arthritis Therapy Based on B Cells.

IF 5.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Drug Design, Development and Therapy Pub Date : 2025-09-06 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S527687
Yongqi Liang, Menglei Zha, Qifeng Liu, Zhifei Lai, Lei Li, Yiming Shao, Jianbo Sun
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引用次数: 0

Abstract

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.

基于B细胞的类风湿关节炎治疗。
类风湿性关节炎(RA)是一种慢性自身免疫性疾病,以持续滑膜炎症、关节破坏和进行性残疾为特征。虽然目前的治疗方法——包括皮质类固醇、疾病改善抗风湿药物(DMARDs)、非甾体抗炎药(NSAIDs)和生物制剂——提供了症状缓解,但它们的临床应用仍然受到诸如全身毒性、耐药性和累积不良反应等实质性限制。这些挑战强调了对具有更高安全性和有效性的新型治疗策略的迫切需要。RA的发病机制涉及多方面的免疫失调,新出现的证据强调了B淋巴细胞在疾病发生和进展中的核心作用。尽管像利妥昔单抗这样的B细胞靶向治疗显示出临床疗效,但关于B细胞亚群在RA发病机制中的精确免疫功能及其作为可转化治疗靶点的潜力,仍存在未解之谜。本文综述了风湿性关节炎的临床负担、常规治疗的局限性以及对B细胞病理生理学的不断发展的认识。我们批判性地评估已建立的B细胞定向干预-包括B细胞耗竭,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信息。
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来源期刊
Drug Design, Development and Therapy
Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY
CiteScore
9.00
自引率
0.00%
发文量
382
审稿时长
>12 weeks
期刊介绍: Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.
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