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Citations to this article

Treatment of murine lupus with cDNA encoding IFN-γR/Fc
Brian R. Lawson, … , Dwight H. Kono, Argyrios N. Theofilopoulos
Brian R. Lawson, … , Dwight H. Kono, Argyrios N. Theofilopoulos
Published January 15, 2000
Citation Information: J Clin Invest. 2000;106(2):207-215. https://doi.org/10.1172/JCI10167.
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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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IH Tarner, CG Fathman
Current Opinion in Immunology 2001
Evidence for an Interferon-Inducible Gene, Ifi202, in the Susceptibility to Systemic Lupus
SJ Rozzo, JD Allard, D Choubey, TJ Vyse, S Izui, G Peltz, BL Kotzin
Immunity 2001
Reduction of Serum Interferon (IFN)-γ Concentration and Lupus Development in NZBxNZWF1Mice by Lactic Dehydrogenase Virus Infection
T Hayashi, K Hasegawa, A Ohta, K Maeda
Journal of Comparative Pathology 2001
Interferon-γ polymorphisms in systemic lupus erythematosus
JY Lee, D Goldman, LM Piliero, M Petri, KE Sullivan
Genes and Immunity 2001
The Role of αβ + T Cells and Homeostatic T Cell Proliferation in Y-Chromosome-Associated Murine Lupus
BR Lawson, SI Koundouris, M Barnhouse, W Dummer, R Baccala, DH Kono, AN Theofilopoulos
Journal of immunology (Baltimore, Md. : 1950) 2001
Role of Cyclin Kinase Inhibitor p21 in Systemic Autoimmunity
ML Santiago-Raber, BR Lawson, W Dummer, M Barnhouse, S Koundouris, CB Wilson, DH Kono, AN Theofilopoulos
Journal of immunology (Baltimore, Md. : 1950) 2001
Gene therapy in the treatment of autoimmune diseases
GC Tsokos, GT Nepom
Journal of Clinical Investigation 2000
Uveitis
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Expert Opinion on Therapeutic Targets 2000
Treatment of murine lupus with cDNA encoding IFN-?R/Fc
C Smythe
Arthritis Research & Therapy 2000

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