title: Dysregulation of antiviral helicase pathways in systemic lupus erythematosus.
abstract: 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.
authors.affiliation: Rheumatology Unit, Department of Medicine, Faculty of Medical Science, State University of Campinas Campinas, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Oliveira
authors.affiliation: Rheumatology Unit, Department of Medicine, Faculty of Medical Science, State University of Campinas Campinas, Brazil.
authors.forename: Nailú A
authors.initials: NA
authors.lastname: Sinicato
authors.affiliation: Rheumatology Unit, Department of Medicine, Faculty of Medical Science, State University of Campinas Campinas, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Postal
authors.affiliation: Rheumatology Unit, Department of Medicine, Faculty of Medical Science, State University of Campinas Campinas, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Appenzeller
authors.affiliation: Mayo Clinic, Division of Rheumatology, Department of Immunology Rochester, MN, USA.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Niewold
keywords: antiviral helicase; interferon; systemic lupus erythematosus