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<p>Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic, erosive synovitis. While significant progress and breakthroughs have been made in disease diagnosis through basic research and clinical practice, approximately 30%–40% of seronegative RA patients still experience diagnostic delays and fail to achieve treatment targets. In recent years, the discovery of novel autoantibodies and biomarkers has opened new avenues for addressing this challenge. These molecules target post-translationally modified (PTM) antigens other than citrullinated proteins, while some are recognized independently of PTMs. They are also linked to key pathological processes such as inflammation, metabolism, and signal transduction. Experimental and clinical evidence directly or indirectly supports their regulatory roles in these processes. This review systematically summarizes the discovery process, target antigen functions, diagnostic efficacy, and roles in the pathogenesis of these novel antibodies. It focuses on their significant potential to improve the diagnosis rate of seronegative RA, predict disease progression and bone erosion risk, as well as define new disease subtypes. However, the precise mechanisms by which these autoantibodies contribute to RA pathogenesis remain to be fully elucidated. Furthermore, this article discusses current challenges, including detection standardization and clinical validation, and offers an outlook on the prospects for precision diagnosis and personalized treatment based on multi-autoantibody panels.</p>

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Novel Autoantibodies in Rheumatoid Arthritis: Translational Prospects from Seronegative Breakthrough to Precision Diagnosis and Treatment

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月5日

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  • Zewen Wu,
  • Huijing Zhang,
  • Jiapeng Zhang,
  • Xueyan Gong,
  • Zhen Jia,
  • Chong Gao,
  • Liyun Zhang

摘要

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic, erosive synovitis. While significant progress and breakthroughs have been made in disease diagnosis through basic research and clinical practice, approximately 30%–40% of seronegative RA patients still experience diagnostic delays and fail to achieve treatment targets. In recent years, the discovery of novel autoantibodies and biomarkers has opened new avenues for addressing this challenge. These molecules target post-translationally modified (PTM) antigens other than citrullinated proteins, while some are recognized independently of PTMs. They are also linked to key pathological processes such as inflammation, metabolism, and signal transduction. Experimental and clinical evidence directly or indirectly supports their regulatory roles in these processes. This review systematically summarizes the discovery process, target antigen functions, diagnostic efficacy, and roles in the pathogenesis of these novel antibodies. It focuses on their significant potential to improve the diagnosis rate of seronegative RA, predict disease progression and bone erosion risk, as well as define new disease subtypes. However, the precise mechanisms by which these autoantibodies contribute to RA pathogenesis remain to be fully elucidated. Furthermore, this article discusses current challenges, including detection standardization and clinical validation, and offers an outlook on the prospects for precision diagnosis and personalized treatment based on multi-autoantibody panels.