Removal of glomerular immune complex deposits by excess antigen in chronic mouse model of immune complex disease

The removal of glomerular immune complex deposits by administering excess antigen was studied in a chronic mouse model of immune complex disease. C57BL 6/J female mice were first immunized with aggregated human serum albumin (HSA) in adjuvant and were chronically given 1.0 mg of monomeric HSA intraperitoneally three times weekly. Mild proteinuria developed after 2 weeks of chronic antigen administration. A left nephrectomy was performed after 2, 4, and 6 weeks of chronic antigen. Progressive hypercellularity and sclerotic change were noted by light microscopy. Glomerular deposits of antigen (HSA), mouse IgG, and mouse C3 were found at all times by immunofluorescence microscopy. By electron microscopy mesangial deposits were present at all times. Subepithelial deposits were first noted in three of five mice examined after 4 weeks of chronic antigen and in four of six mice examined after 6 weeks of chronic antigen. After nephrectomy after 2, 4, and 6 weeks of chronic antigen administration mice received excess antigen by injection of 25 mg of monomeric HSA intravenously every 24 hours. The animals were sacrificed after 12, 24, 48, or 72 hours to obtain the remaining kidney so that each animal served as its own control. Immunofluorescence studies demonstrated that after 2 and 4 weeks of chronic antigen deposits of HSA and mouse IgG were successfully removed by excess antigen within 24 to 48 hours. After 6 weeks of chronic antigen, deposits of HSA and mouse IgG persisted through 72 hours of excess antigen. The effect of administering excess antigen on glomerular ultrastructure demonstrated that mesangial deposits after 2 weeks of chronic antigen and both mesangial and subepithelial deposits after 4 weeks of chronic antigen were either decreased or completely removed. After 6 weeks of chronic antigen both mesangial and subepithelial deposits were either not removed or incompletely removed by excess antigen. Possible explanations for progressive difficulty in removing glomerular deposits with excess antigen include (a) an increase in glomerular connective tissue leading to sclerosis and (b) the participation of other antigen-antibody systems in the deposition process, since the persistence appeared greater for mouse IgG deposits than for HSA (antigen) deposits.