Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by an autoimmune response in the joints and an exacerbation of cytokine responses. A minority of patients with RA experience spontaneous remission, but most will show moderate/high disease activity, with aggressive joint damage and multiple systemic manifestations. There is thus is a great need to identify prognostic biomarkers for disease risk to improve diagnosis and prognosis, and to inform on the most appropriate therapy. Here we focused on suppressor of cytokine signaling 1 (SOCS1), a physiological negative regulator of cytokines that modulates cell activation. Using four independent cohorts of patients with arthritis, we characterized the correlation between SOCS1 mRNA levels and clinical outcome. We found a significant inverse correlation between SOCS1 mRNA expression and disease activity throughout the follow-up of patients with RA. Lower baseline SOCS1 levels were associated with poorer disease control in response to methotrexate and other conventional synthetic disease-modifying anti-rheumatic drugs in early arthritis, and to rituximab in established (active) RA. Moreover, we identified several single nucleotide polymorphisms in the SOCS1 gene that correlated with SOCS1 mRNA expression, and that might identify those patients with early arthritis that fulfill RA classification criteria. One of them, rs4780355, is in linkage disequilibrium with a microsatellite (TTTTC)₃₋₅, mapped 0.9 kb downstream of the SNP, and correlated with reduced SOCS1 expression in vitro. Overall, our data support the association between SOCS1 expression and disease progression, disease severity and response to treatment in RA. These observations underlie the relevance of SOCS1 mRNA levels for stratifying patients prognostically and guiding therapeutic decisions.

类风湿性关节炎 (RA) 是一种慢性炎症性疾病，其特征在于关节中的自身免疫反应和细胞因子反应的加剧。少数 RA 患者会自发缓解，但大多数会表现出中度/高度疾病活动，伴有侵袭性关节损伤和多种全身表现。因此，非常需要确定疾病风险的预后生物标志物，以改善诊断和预后，并告知最合适的治疗方法。在这里，我们专注于细胞因子信号 1 (SOCS1) 的抑制因子，这是一种调节细胞活化的细胞因子的生理负调节因子。使用四个独立的关节炎患者队列，我们​​描述了两者之间的相关性SOCS1mRNA水平和临床结果。我们发现两者之间存在显着的负相关SOCS1在 RA 患者的整个随访过程中的 mRNA 表达和疾病活动。较低的基线SOCS1甲氨蝶呤和其他常规合成的改善疾病的抗风湿药物治疗早期关节炎，以及利妥昔单抗治疗已建立的（活动性）类风湿性关节炎患者的疾病控制较差。此外，我们还发现了几个单核苷酸多态性SOCS1相关的基因SOCS1mRNA 表达，这可能会识别出符合 RA 分类标准的早期关节炎患者。其中之一，rs4780355，与微卫星 (TTTTC) _3-5处于连锁不平衡状态，映射到 SNP 下游 0.9 kb，并与还原相关SOCS1表达体外. 总体而言，我们的数据支持之间的关联SOCS1RA 中的表达和疾病进展、疾病严重程度和对治疗的反应。这些观察是相关性的基础SOCS1用于对患者进行预后分层和指导治疗决策的 mRNA 水平。