CTLA4IgG gene delivery prevents autoantibody production and lupus nephritis in MRL/lpr mice.
MRL/MP-lpr/lpr (MRL/lpr) mice spontaneously develop an autoimmune syndrome closely resembling systemic lupus erythematosus (SLE) in humans, characterized by hypergammaglobulinemia, various autoantibody production, and the development of fatal glomerulonephritis. We have previously demonstrated that systemic administration of soluble form of CTLA4IgG prevented autoantibody-related diseases in MRL/lpr mice. To test the potential protective effects of CTLA4IgG gene delivery on the development of lupus nephritis, we injected MRL/lpr mice with a recombinant adenovirus vector containing CTLA4IgG gene, Adex1CACTLA4IgG (AdCTLA4IgG). It was demonstrated that a single administration of intravenous injection of AdCTLA4IgG into MRL/lpr mice resulted in almost complete amelioration of lupus nephritis.
Takiguchi
M
M
Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Murakami
M
M
Nakagawa
I
I
Saito
I
I
Hashimoto
A
A
Uede
T
T
D000069594:Abatacept; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000097:blood / Q000235:genetics*; D001323:Autoantibodies / Q000096:biosynthesis*; D060908:CTLA-4 Antigen; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D018796:Immunoconjugates; D007677:Kidney Function Tests; D008181:Lupus Nephritis / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001323:Autoantibodies; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D000069594:Abatacept