Robert Marie, Miossec Pierre
Department of Clinical Immunology and Rheumatology, Immunogenomics and Inflammation Research Unit EA 4130, University of Lyon 1, Hôpital Edouard Herriot, Lyon, France.
Front Med (Lausanne). 2019 Jan 14;5:364. doi: 10.3389/fmed.2018.00364. eCollection 2018.
Interleukin (IL)-17A has a direct contribution in early induction and late chronic stages of various inflammatory diseases. and experiments have first characterized its local effects on different cell types and then its systemic effects. For instance, IL-17 axis is now identified as a key driver of psoriasis through its effects on keratinocytes. Similar observations apply for rheumatoid arthritis (RA) where IL-17A triggers changes in the synovium that lead to synovitis and maintain local inflammation. These results have prompted the development of biologics to target this cytokine. However, while convincing studies are reported on the efficacy of IL-17 inhibitors in psoriasis, there are conflicting results in RA. Patient heterogeneity but also the involvement of mediators that regulate IL-17 function may explain these results. Therefore, new tools and concepts are required to identify patients that could benefit from these IL-17 targeted therapies in RA and the development of predictive biomarkers of response has started with the emergence of various bioassays. Current strategies are also focusing on synovial biopsies that may be used to stratify patients. From local to systemic levels, new approaches are developing and move the field of RA management into the era of precision medicine.
白细胞介素（IL）-17A在多种炎症性疾病的早期诱导和晚期慢性阶段都有直接作用。实验首先明确了其对不同细胞类型的局部作用，随后又确定了其全身作用。例如，IL-17轴现已被确认为银屑病的关键驱动因素，因为它对角质形成细胞有影响。类风湿关节炎（RA）也有类似情况，IL-17A引发滑膜变化，导致滑膜炎并维持局部炎症。这些结果促使了针对这种细胞因子的生物制剂的研发。然而，虽然有关于IL-17抑制剂在银屑病中疗效的令人信服的研究报告，但在RA中却存在相互矛盾的结果。患者的异质性以及调节IL-17功能的介质的参与可能解释了这些结果。因此，需要新的工具和概念来识别可能从RA中这些针对IL-17的治疗中获益的患者，并且随着各种生物测定方法的出现，已经开始开发反应预测生物标志物。当前的策略也集中在可能用于对患者进行分层的滑膜活检上。从局部到全身层面，新的方法正在不断发展，将RA管理领域带入精准医学时代。
