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Murine Model of CD40-activation of B cells
Published on: March 5, 2010
Treatment of murine lupus with cDNA encoding IFN-gammaR/Fc
B R Lawson1, G J Prud'homme, Y Chang
1Department of Immunology, The Scripps Research Institute, La Jolla, California, USA.
The Journal of Clinical Investigation
|July 21, 2000
Summary
Gene therapy using interferon-gamma receptor (IFN-gammaR)/Fc successfully reversed lupus progression in mice. This promising approach offers potential for treating autoimmune diseases like lupus.
Area of Science:
- Immunology
- Autoimmune Diseases
- Gene Therapy
Background:
- Interferon-gamma (IFN-gamma) is a key cytokine in the pathogenesis of autoimmune diseases, including lupus.
- Genetic deletion of IFN-gamma or its receptor (IFN-gammaR) reduces lupus severity in mouse models, indicating therapeutic potential.
Purpose of the Study:
- To evaluate the efficacy of intramuscular plasmid-based IFN-gammaR/Fc gene therapy in preventing and treating lupus in MRL-Fas(lpr) mice.
Main Methods:
- Mice received intramuscular injections of plasmids encoding IFN-gammaR/Fc.
- Electroporation was used to enhance gene expression at the injection site.
- Therapy was initiated at pre-disease and advanced stages of lupus.
Main Results:
- IFN-gammaR/Fc therapy significantly reduced serum IFN-gamma levels and lupus manifestations (autoantibodies, lymphoid hyperplasia, glomerulonephritis, mortality).
- Treatment was most effective when initiated at the pre-disease stage, especially with electroporation.
- Remarkably, advanced-stage lupus was arrested and ameliorated by the therapy.
Conclusions:
- Nonviral gene therapy with IFN-gammaR/Fc can effectively retard lupus development and progression in a mouse model.
- This approach demonstrates significant disease reversal, offering a promising therapeutic strategy for lupus and other autoimmune/inflammatory conditions.

