Mary Kirkland Center for Lupus Research, Rheumatology Division, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
Rheum Dis Clin North Am. 2010 Feb;36(1):173-86, x. doi: 10.1016/j.rdc.2009.12.008.
The long history of elevated interferon (IFN)-alpha in association with disease activity in patients who have systemic lupus erythematosus (SLE) has assumed high significance in the past decade, with accumulating data strongly supporting broad activation of the type I IFN pathway in cells of patients who have lupus, and association of IFN pathway activation with significant clinical manifestations of SLE and increased disease activity based on validated measures. In addition, a convincing association of IFN pathway activation with the presence of autoantibodies specific for RNA-binding proteins has contributed to delineation of an important role for Toll-like receptor activation by RNA-containing immune complexes in amplifying innate immune system activation and IFN pathway activation. Although the primary triggers of SLE and the IFN pathway remain undefined, rapid progress in lupus genetics is helping define lupus-associated genetic variants with a functional relationship to IFN production or response in patients. Together, the explosion of data and understanding related to the IFN pathway in SLE have readied the lupus community for translation of those insights to improved patient care. Patience will be needed to allow collection of clinical data and biologic specimens across multiple clinical centers required to support testing of IFN activity, IFN-inducible gene expression and chemokine gene products as candidate biomarkers. Meanwhile, promising clinical trials are moving forward to test the safety and efficacy of monoclonal antibody inhibitors of IFN-alpha. Other therapeutic approaches to target the IFN pathway may follow close behind.
在过去的十年中，系统性红斑狼疮 (SLE) 患者疾病活动与干扰素 (IFN)-α升高的悠久历史具有重要意义，越来越多的数据强烈支持狼疮患者细胞中 I 型 IFN 途径的广泛激活，以及 IFN 途径激活与 SLE 的显著临床表现和基于验证措施的疾病活动增加之间存在关联。此外，IFN 途径激活与针对 RNA 结合蛋白的自身抗体的存在之间的令人信服的关联有助于阐明 RNA 免疫复合物激活 Toll 样受体在放大固有免疫系统激活和 IFN 途径激活中的重要作用。尽管 SLE 的主要触发因素和 IFN 途径仍未确定，但狼疮遗传学的快速进展有助于确定与患者 IFN 产生或反应具有功能关系的狼疮相关遗传变异体。总之，SLE 中 IFN 途径的数据和理解的爆发使狼疮界有能力将这些见解转化为改善患者护理。需要耐心等待，以便在多个临床中心收集支持 IFN 活性、IFN 诱导基因表达和趋化因子基因产物作为候选生物标志物检测所需的临床数据和生物样本。同时，有前途的临床试验正在向前推进，以测试 IFN-α单克隆抗体抑制剂的安全性和有效性。紧随其后的可能是针对 IFN 途径的其他治疗方法。
