a Department of Rheumatology , University Hospital Schleswig-Holstein , Lübeck , Germany.
Expert Rev Clin Immunol. 2016 Nov;12(11):1153-1160. doi: 10.1080/1744666X.2016.1199957. Epub 2016 Jun 23.
The pathogenesis of systemic lupus erythematosus (SLE) involves an acquired deficiency of the cytokine IL-2, an essential growth and survival factor for regulatory T cells (Treg), which play an important role in the control of autoimmunity in SLE. In contrast to currently available therapies that broadly suppress the immune system, low-dose IL-2 therapy in SLE aims to compensate the pre-existing IL-2 deficiency and thus to restore a physiological state, where Treg can regain their ability to efficiently counteract autoimmunity. Areas covered: Here we summarize key findings that led to the development of this novel therapeutic concept and will highlight the key rationales for the clinical translation of low-dose IL-2 therapy in SLE. Expert commentary: The concept of low-dose IL-2 therapy in SLE has evolved from pathophysiological findings and thus can be considered a selective biological treatment strategy in SLE. Preliminary results from phase I/II studies are promising by proving selective Treg expansion and by providing first evidence for the clinical efficacy of low-dose IL-2 therapy in SLE.
系统性红斑狼疮(SLE)的发病机制涉及细胞因子 IL-2 的获得性缺乏,IL-2 是调节性 T 细胞(Treg)的重要生长和存活因子,在 SLE 中对自身免疫的控制起着重要作用。与目前广泛抑制免疫系统的现有疗法不同,SLE 的低剂量 IL-2 疗法旨在补偿先前存在的 IL-2 缺乏,从而恢复 Treg 能够有效对抗自身免疫的生理状态。
在这里,我们总结了导致这一新治疗概念发展的关键发现,并将重点阐述低剂量 IL-2 治疗 SLE 的临床转化的关键原理。
SLE 中的低剂量 IL-2 疗法的概念源自病理生理学发现,因此可以被认为是 SLE 中的一种选择性生物治疗策略。来自 I/II 期研究的初步结果很有希望,证明了选择性 Treg 扩增,并为 SLE 中低剂量 IL-2 治疗的临床疗效提供了初步证据。