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Treatment of murine lupus with cDNA encoding IFN-γR/Fc
Brian R. Lawson, Gerald J. Prud’homme, Yigang Chang, Humphrey A. Gardner, Jason Kuan, Dwight H. Kono, Argyrios N. Theofilopoulos
Brian R. Lawson, Gerald J. Prud’homme, Yigang Chang, Humphrey A. Gardner, Jason Kuan, Dwight H. Kono, Argyrios N. Theofilopoulos
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Article

Treatment of murine lupus with cDNA encoding IFN-γR/Fc

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Abstract

IFN-γ, a pleiotropic cytokine, is a key effector molecule in the pathogenesis of several autoimmune diseases, including lupus. Importantly, deletion of IFN-γ or IFN-γR in several lupus-predisposed mouse strains resulted in significant disease reduction, suggesting the potential for therapeutic intervention. We evaluated whether intramuscular injections of plasmids with cDNA encoding IFN-γR/Fc can retard lupus development and progression in MRL-Faslpr mice. Therapy significantly reduced serum levels of IFN-γ, as well as disease manifestations (autoantibodies, lymphoid hyperplasia, glomerulonephritis, mortality), when treatment was initiated at the predisease stage, particularly when IFN-γR/Fc expression was enhanced by electroporation at the injection site. Remarkably, disease was arrested and even ameliorated when this treatment was initiated at an advanced stage. This therapy represents a rare example of disease reversal and makes application of this nonviral gene therapy in humans with lupus (and perhaps other autoimmune/inflammatory conditions) highly promising.

Authors

Brian R. Lawson, Gerald J. Prud’homme, Yigang Chang, Humphrey A. Gardner, Jason Kuan, Dwight H. Kono, Argyrios N. Theofilopoulos

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