Oliveira Luciana, Sinicato Nailú A, Postal Mariana, Appenzeller Simone, Niewold Timothy B
Rheumatology Unit, Department of Medicine, Faculty of Medical Science, State University of Campinas Campinas, Brazil.
Mayo Clinic, Division of Rheumatology, Department of Immunology Rochester, MN, USA.
Front Genet. 2014 Nov 25;5:418. doi: 10.3389/fgene.2014.00418. eCollection 2014.
In the autoimmune disease systemic lupus erythematosus (SLE), our normal antiviral defenses are inappropriately activated, resulting in over-activity of the type I interferon (IFN) pathway. This increased activity of the type I IFN pathway is an important primary pathogenic factor in the disease. Emerging evidence has implicated the antiviral helicases in this process. The antiviral helicases normally function as nucleic acid receptors in viral immunity. Genetic variations in antiviral helicase genes have been associated with SLE, supporting the idea that helicase pathways are involved in the primary pathogenesis of SLE. Studies have documented functional consequences of these genetic variations within the type I IFN pathway in human cell lines and SLE patients. In this review, we summarize the function of helicases in the anti-viral immune response, and how this response is dysregulated in SLE patients. In particular, we will focus on known functional genetic polymorphisms in the IFIH1 (MDA5) and mitochondrial antiviral signaling protein genes which have been implicated in human SLE. These data provide fascinating evidence for dysregulation of helicase-mediated innate immunity in SLE, and may support novel therapeutic strategies in the disease.
在自身免疫性疾病系统性红斑狼疮（SLE）中，我们正常的抗病毒防御机制被不恰当地激活，导致I型干扰素（IFN）通路过度活跃。I型干扰素通路的这种活性增加是该疾病的一个重要主要致病因素。新出现的证据表明抗病毒解旋酶参与了这一过程。抗病毒解旋酶通常在病毒免疫中作为核酸受体发挥作用。抗病毒解旋酶基因的遗传变异与SLE有关，支持了解旋酶通路参与SLE主要发病机制的观点。研究记录了这些遗传变异在人类细胞系和SLE患者I型干扰素通路中的功能后果。在本综述中，我们总结了解旋酶在抗病毒免疫反应中的功能，以及SLE患者中这种反应是如何失调的。特别是，我们将重点关注IFIH1（MDA5）和线粒体抗病毒信号蛋白基因中已知的功能性遗传多态性，这些基因与人类SLE有关。这些数据为SLE中解旋酶介导的先天免疫失调提供了引人入胜的证据，并可能支持该疾病的新治疗策略。
