Type I interferon as a target of treatment in SLE.
Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by the production of antibodies against a spectrum of autoantigens. Recent evidence suggests that type-I interferons (IFN-I) are critically involved in the pathogenesis of SLE. Initially recognized for their anti-viral properties, IFN-I play important roles in immunity and autoimmunity by promoting DC maturation, T cell survival, and antibody production. Onset of SLE has been reported in patients with hepatitis or neoplastic diseases undergoing treatment with recombinant IFN-I while elevated serum IFN-I and IFN-stimulated gene expression are found in approximately 2/3 of SLE patients. This interferon signature is clinically important as it correlates with disease activity and renal as well as CNS involvement. Supporting these findings, genetic abnormalities resulting in increased IFN-I production and/or signaling are associated with SLE. In view of the accumulating evidence linking IFN-I to the pathogenesis of SLE, targeting of IFN-I may be beneficial therapeutically while avoiding the side effects associated with conventional immunosuppressive therapy. To this end, IFN-I and IFN-producing cells as well as IFN-inducers and molecules of the IFN signaling pathway may all serve as potential therapeutic targets. Several anti-IFN-I approaches have already shown promising effects in animal studies and clinical trials will likely begin in the near future.
Lee
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Division of Rheumatology & Clinical Immunology, University of Florida, PO Box 100221, Gainesville, FL 32610-0221, USA.
Reeves
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D000818:Animals; D006801:Humans; D007155:Immunologic Factors / Q000502:physiology; D007370:Interferon Type I / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D007155:Immunologic Factors; D007370:Interferon Type I