Vieira-Sousa Elsa, Gerlag Danielle M, Tak Paul P
Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Portugal.
Open Rheumatol J. 2011;5:115-22. doi: 10.2174/1874312901105010115. Epub 2011 Dec 30.
The recognition of the synovial tissue, as the primary target of inflammation in RA, has driven research in this field, not only to clarify the disease pathogenesis but also to evaluate local changes in response to treatment. Special interest has been given to the identification of sensitive synovial biomarkers that could be of help in demonstrating proof of principle in early stages of drug development. Synovial sublining macrophages have been shown to correlate with scores for disease activity in cross-sectional studies. Moreover, decreased disease activity as measured by the disease activity score evaluated in 28 joints (DAS28) after effective treatment, has consistently been associated with a reduction of the number of CD68+ synovial sublining macrophages across different therapies. This observation highlights a possible final common pathway in the mechanism of action of various therapies and supports the notion that macrophages have a central role in RA pathogenesis.When considering experimental therapies, the study of serial synovial biopsies in relatively small numbers of patients, in the context of proof of principle trials, successfully distinguished between effective and ineffective treatments. This attractive approach can be used during early drug development for screening proposes, supporting which new treatments have higher probability to be beneficial in a large scale clinical trial.In this paper we review the effects of RA treatments on the synovial tissue, including targeted therapies, with particular attention to their effect on synovial biomarkers.
滑膜组织被认为是类风湿性关节炎（RA）炎症的主要靶点，这推动了该领域的研究，不仅是为了阐明疾病发病机制，也是为了评估治疗反应中的局部变化。人们对识别敏感的滑膜生物标志物给予了特别关注，这些标志物有助于在药物开发的早期阶段证明原理。在横断面研究中，滑膜衬里巨噬细胞已被证明与疾病活动评分相关。此外，在有效治疗后，通过28个关节疾病活动评分（DAS28）测量的疾病活动度降低，一直与不同治疗方法中CD68 +滑膜衬里巨噬细胞数量的减少相关。这一观察结果突出了各种治疗作用机制中可能存在的最终共同途径，并支持巨噬细胞在RA发病机制中起核心作用的观点。在考虑实验性治疗时，在原理验证试验的背景下，对相对少量患者进行连续滑膜活检的研究成功地区分了有效治疗和无效治疗。这种有吸引力的方法可用于早期药物开发中的筛选，支持哪些新治疗方法在大规模临床试验中更有可能有益。在本文中，我们综述了RA治疗对滑膜组织的影响，包括靶向治疗，特别关注它们对滑膜生物标志物的影响。
