{"title":"Targeting pathogenic immune cells in rheumatoid arthritis: emerging immunotherapeutic frontiers.","authors":"Yan Dong, Xifang Xu, Sathyamoorthi S, Jindong Dai, Vijayakumar Murugesan, Selvaraj Muthusamy, Kanagaraj Rajalakshmi, Dongwei Zhu","doi":"10.3389/fimmu.2026.1895048","DOIUrl":null,"url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a persistent autoimmune condition that predominantly affects the joints resulting in inflammation, pain and progressive disability. Immunological imbalance, especially the stimulation of pathogenic immune cells, including T and B cells, macrophages, amongst others, is the cause of the disease, as it is critical to the development of the disease. The limitation of traditional anti-RA medications, such as non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), in the treatment of the disease led to the development of more specific medicines. One of the most promising biologic agents, including monoclonal antibodies, cytokine inhibitors and cell-based therapies, are specifically targeting immune cells and inflammatory pathways in RA. This review examines these new immunotherapies, their mechanisms of action, clinical efficacy, and challenges associated with them, including resistance to treatment, safety issues, and the necessity to use personalised therapy. Also, the new immunotherapeutic approaches, which include targeting autoantibodies, gene therapy, and precision medicine, are promising new approaches that could result in more effective and personalised treatments. Finally, the review concludes with a discussion of future directions, where in combination therapies, next-generation biologics, and personalised treatment regimens are also possible and can change the way RA can be managed in the future. To preserve analytical depth, this review explicitly distinguishes established (regulatory-approved) therapies from investigational and experimental approaches and indicates the level of clinical evidence for each.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1895048"},"PeriodicalIF":7.0000,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678509/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fimmu.2026.1895048","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Rheumatoid arthritis (RA) is a persistent autoimmune condition that predominantly affects the joints resulting in inflammation, pain and progressive disability. Immunological imbalance, especially the stimulation of pathogenic immune cells, including T and B cells, macrophages, amongst others, is the cause of the disease, as it is critical to the development of the disease. The limitation of traditional anti-RA medications, such as non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), in the treatment of the disease led to the development of more specific medicines. One of the most promising biologic agents, including monoclonal antibodies, cytokine inhibitors and cell-based therapies, are specifically targeting immune cells and inflammatory pathways in RA. This review examines these new immunotherapies, their mechanisms of action, clinical efficacy, and challenges associated with them, including resistance to treatment, safety issues, and the necessity to use personalised therapy. Also, the new immunotherapeutic approaches, which include targeting autoantibodies, gene therapy, and precision medicine, are promising new approaches that could result in more effective and personalised treatments. Finally, the review concludes with a discussion of future directions, where in combination therapies, next-generation biologics, and personalised treatment regimens are also possible and can change the way RA can be managed in the future. To preserve analytical depth, this review explicitly distinguishes established (regulatory-approved) therapies from investigational and experimental approaches and indicates the level of clinical evidence for each.
期刊介绍:
Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.