title: Emerging therapies for systemic lupus erythematosus--focus on targeting interferon-alpha.
abstract: Current therapies for systemic lupus erythematosus (SLE), a debilitating, potentially lethal, multifactorial systemic autoimmune disease, are limited to suppressing disease activity and are associated with multiple adverse effects. Recent advances in basic and translational sciences have elucidated a crucial role for the interferon-alpha (IFNα) pathway in the pathogenesis of this enigmatic disease. The so-called "type I interferon signature" has emerged as a major risk factor for disease activity of SLE. Multiple genes encoding for molecules within the type I interferon pathway have been associated with SLE in genome wide association studies. In addition, innate immune receptors are thought to be triggered by either endogenous and/or exogenous stimuli that lead to hypersecretion of IFNα. We review the multiple emerging treatment strategies targeting IFNα-related pathways. These include monoclonal antibodies against IFNα, anti-IFNα antibody-inducing vaccines, and inhibitors of Toll-like receptors. We also summarize the current status of these pharmaceutical agents in early clinical trials.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Eben I
authors.initials: EI
authors.lastname: Lichtman
authors.forename: Simon M
authors.initials: SM
authors.lastname: Helfgott
authors.forename: Martin A
authors.initials: MA
authors.lastname: Kriegel
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D051379:Mice; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology
chemical_list: D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; D051193:Toll-Like Receptors