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.
Brian R. Lawson, Gerald J. Prud’homme, Yigang Chang, Humphrey A. Gardner, Jason Kuan, Dwight H. Kono, Argyrios N. Theofilopoulos
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BR Lawson, R Baccala, J Song, M Croft, DH Kono, AN Theofilopoulos |
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IL-12 Gene Therapy Using an Electrically Mediated Nonviral Approach Reduces Metastatic Growth of Melanoma
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Using Single-Gene Deletions to Identify Checkpoints in the Progression of Systemic Autoimmunity
KM Pollard, P Hultman, DH Kono |
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TN JØrgensen, MR Gubbels, BL Kotzin |
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Inhibition of Lupus by Genetic Alteration of the Interferon-α/β Receptor
DH Kono, R Baccala, AN Theofilopoulos |
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Microarray Analysis of Interferon-regulated Genes in SLE
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Autoimmunity | 2003 |
Synthetic CpG oligodeoxynucleotides accelerate the development of lupus nephritis during preactive phase in NZB ×NZWF1 mice
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Intramuscular gene transfer of soluble B7.1/IgG1 fusion cDNA induces potent antitumor immunity as an adjuvant for DNA vaccination
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Immunopathology and the gene therapy of lupus
RA Mageed, GJ Prud'homme |
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Cytokines and Chemokines in Autoimmune Disease
P Santamaria |
2003 | |
IL-12 Deficiency in MRL- Faslpr Mice Delays Nephritis and Intrarenal IFN-γ Expression, and Diminishes Systemic Pathology
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Journal of immunology (Baltimore, Md. : 1950) | 2003 |
Essential role of monocyte chemoattractant protein-1 in development of restenotic changes (neointimal hyperplasia and constrictive remodeling) after balloon angioplasty in hypercholesterolemic rabbits
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GJ Prud'homme, Y Chang, X Li |
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CE Carvalho-Pinto, MI García, M Mellado, JM Rodríguez-Frade, J Martín-Caballero, J Flores, C Martínez-A, D Balomenos |
Journal of immunology (Baltimore, Md. : 1950) | 2002 |
Direct Transfer of p65 into T Lymphocytes from Systemic Lupus Erythematosus Patients Leads to Increased Levels of Interleukin-2 Promoter Activity
TM Herndon, YT Juang, EE Solomou, SW Rothwell, MF Gourley, GC Tsokos |
Clinical Immunology | 2002 |
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IH Tarner, CG Fathman |
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JS Smolen |
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Anticytokine gene therapy of autoimmune diseases
GJ Prud’homme, BR Lawson, AN Theofilopoulos |
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AN Theofilopoulos, S Koundouris, DH Kono, BR Lawson |
Arthritis research | 2001 |
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M El-Amine, ME Melo, DW Scott |
Clinical Immunology | 2001 |
Immunotherapeutic gene transfer into muscle
GJ Prud'homme, BR Lawson, Y Chang, AN Theofilopoulos |
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IH Tarner, CG Fathman |
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JY Lee, D Goldman, LM Piliero, M Petri, KE Sullivan |
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The Role of αβ + T Cells and Homeostatic T Cell Proliferation in Y-Chromosome-Associated Murine Lupus
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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 |
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GC Tsokos, GT Nepom |
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CE Egwuagu, JA Smith |
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C Smythe |
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