title: Type I interferon and systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease associated with multiple immunologic abnormalities. Prominent among these is upregulation of type I interferon (IFN)?a powerful immune adjuvant. IFN is, in part, produced in SLE in response to autoantigens in the form of self-nucleic acids and their associated nuclear proteins. Sources of these autoantigens include apoptotic and necrotic cells as well as neutrophils undergoing a specific form of cell death called NETosis. Although plasmacytoid dendritic cells are the main producers of IFN-a, other cells are important regulators of this process. Both genetic and environmental risk factors play a role in the development and pathogenesis of SLE. Further highlighting the importance of IFN, candidate gene and genome-wide association studies have identified a number of genes involved in type I IFN pathways associated with SLE. In this review, 3 monogenic deficiencies that result in lupus-like phenotypes and several polygenic variants that have been consistently associated with SLE are highlighted, and the relationship of these genes to IFN-a production is discussed. Clinical associations of the type I IFN pathway and the use of IFN-blocking agents as therapeutic agents in SLE are also reviewed.
authors.affiliation: Division of Rheumatology, University of Washington, Seattle, USA. elkon@u.washington.edu
authors.forename: Keith B
authors.initials: KB
authors.lastname: Elkon
authors.forename: Vivian V
authors.initials: VV
authors.lastname: Stone
mesh_terms: D000818:Animals; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D007370:Interferon Type I