Triaille Clément, Lauwerys Bernard R
Pôle de Pathologies Rhumatismales Systémiques et Inflammatoires, Institut de Recherches Expérimentales et Cliniques, Université catholique de Louvain, Brussels, Belgium.
Department of Pediatric Haematology and Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Front Med (Lausanne). 2019 Mar 21;6:46. doi: 10.3389/fmed.2019.00046. eCollection 2019.
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease targeting the joints. Current treatment strategies are based on clinical, biological and radiological features, yet still fail to reach the goal of early low disease activity in a significant number of cases. Hence, there is a need for refining current treatment algorithms, using accurate markers of response to therapy. Because RA induces histological and molecular alterations in the synovium even before apparition of clinical symptoms, synovial biopsies are a promising tool in the search of such new biomarkers. Histological and molecular characteristics of RA synovitis are heterogeneous. Variations in synovial lining layer hyperplasia, in cellular infiltration of the sublining by immune cells of myeloid and lymphoid lineages, and in molecular triggers of these features are currently categorized using well-defined pathotypes: myeloid, lymphoid, fibroid and pauci-immune. Here, we first bring the plasticity of RA synovitis under scrutiny, i.e., how variations in synovial characteristics are associated with relevant clinical features (disease duration, disease activity, effects of therapies, disease severity). Primary response to a specific drug could be, at least theoretically, related to the representation of the molecular pathway targeted by the drug in the synovium. Alternatively, absence of primary response to a specific agent could be due to disease severity, i.e., overrepresentation of all synovial molecular pathways driving disease activity overwhelming the capacity of any drug to block them. Using this theoretical frame, we will highlight how the findings of previous studies trying to link response to therapy with synovial changes provide promising perspectives on bridging the gap to personalized medicine in RA.
类风湿关节炎（RA）是一种以关节为靶点的慢性全身性炎症性疾病。目前的治疗策略基于临床、生物学和放射学特征，但在许多病例中仍未能实现早期低疾病活动度的目标。因此，需要利用准确的治疗反应标志物来完善当前的治疗算法。由于RA甚至在临床症状出现之前就会引起滑膜的组织学和分子改变，滑膜活检是寻找此类新生物标志物的一种有前景的工具。RA滑膜炎的组织学和分子特征是异质性的。目前，滑膜衬里层增生、骨髓和淋巴谱系免疫细胞对滑膜下层的细胞浸润以及这些特征的分子触发因素的变化，是根据明确的病理类型进行分类的：髓样、淋巴样、纤维样和少免疫型。在此，我们首先仔细研究RA滑膜炎的可塑性，即滑膜特征的变化如何与相关临床特征（疾病持续时间、疾病活动度、治疗效果、疾病严重程度）相关联。至少在理论上，对特定药物的初始反应可能与该药物在滑膜中靶向的分子途径的表现有关。或者，对特定药物无初始反应可能是由于疾病严重程度，即所有驱动疾病活动的滑膜分子途径的过度表达压倒了任何药物阻断它们的能力。利用这一理论框架，我们将强调先前试图将治疗反应与滑膜变化联系起来的研究结果如何为弥合RA个性化医疗的差距提供了有前景的观点。
