Treatment with dsDNA-anti-dsDNA antibody complexes extends survival, decreases anti-dsDNA antibody production and reduces severity of nephritis in MRLlpr mice

Abstract

Lupus nephritis results from the deposition on the glomerular basement membrane of antibodies cross-reacting with dsDNA. In an attempt to suppress the production of such antibodies in the MRLlpr mouse strain, mice were treated by injections of dsDNA-anti-dsDNA antibody complexes formed in an excess of syngeneic polyclonal antibodies to increase the immunogenicity of idiotypes. A first group of mice was treated after the onset of high-affinity anti-dsDNA IgG antibodies (3 months). We show here that fortnightly injections of dsDNA-anti-dsDNA antibody complexes significantly extend mouse survival over that of two control groups treated with either the carrier buffer or with sham complexes. Treated mice produced 5-fold less anti-dsDNA antibodies than control mice and presented a reduced nephritis activity index at the age of 7 months. Specific anti-idiotypic antibody levels were not modified in the treated group, while showing a sharp decrease in the control group between months 6 and 7. Mice of a second group were started on injections of dsDNA-anti-dsDNA complexes at the age of 4 months when nephritis was already ongoing, and were followed until death while receiving fortnightly injections. Forty percent of the treated mice were still alive after one year, while none of the control mice survived. dsDNA-anti-dsDNA complexes have therefore the potential of reducing the production of anti-dsDNA antibody production and the severity of nephritis in MRLlpr mice. These findings could be relevant for the treatment of human lupus.