重新审视系统性及皮肤型红斑狼疮中的干扰素轴：从靶向治疗到真实世界临床实践。
完整摘要 · 中文译文
多年来，系统性红斑狼疮（SLE）的发病机制主要从适应性免疫的角度进行解释，重点在于T细胞和B细胞耐受的破坏、自身抗体的产生、免疫复合物的沉积以及补体激活。然而，对SLE免疫发病机制理解的一个重大转变是认识到固有免疫激活，特别是I型干扰素（IFN-I）轴，提供了核酸感知、抗病毒样免疫激活与组织炎症之间的机制联系。尽管多种方法已证明具有生物学活性并为IFN-I通路的治疗性调控提供了概念验证，阿尼鲁单抗——一种靶向IFNAR1的单克隆抗体——目前代表了最具临床验证性的策略，也是基于其在III期试验中的疗效而唯一获批用于SLE的IFN-I靶向治疗。在这篇综述中，我们重新审视SLE和皮肤型红斑狼疮中的IFN-I轴，特别关注其靶向治疗。
完整摘要 · 英文原文
For many years, systemic lupus erythematosus (SLE) pathogenesis was interpreted primarily through the lens of adaptive immunity, with emphasis on disruption of T- and B-cell tolerance, autoantibody production, immune-complex deposition, and complement activation. However, a major shift in the understanding of SLE immunopathogenesis has been the recognition that innate immune activation, and particularly the type I interferon (IFN-I) axis, provides a mechanistic link between acid sensing, antiviral-like immune activation, and tissue inflammation. While several approaches have demonstrated biological activity and provided proof-of-concept for therapeutic modulation of the IFN-I pathway, anifrolumab, a monoclonal antibody targeting IFNAR1, currently represents the most clinically validated strategy and the only approved IFN-I-targeted therapy for SLE, based on its efficacy in phase III trials. In this review article, we revisit the IFN-I axis in SLE and cutaneous lupus erythematosus, with special emphasis on its targeted therapies.