Glomerular localization of preformed immune complexes prepared with anionic antibodies or with cationic antigens

The glomerular basement membrane presents a highly anionic surface to circulation. The effects of anionic antibody and cationic antigen in preformed immune complexes prepared at 5-fold antigen excess were investigated in separate experiments in mice. Anionized antibodies (isoelectric point 4 to 6) to human serum albumin were prepared by acetylation and immune complexes produced in vitro. Blood clearance kinetics and glomerular immunofluorescence patterns of these immune complexes were not affected by anionization . Electron microscopy revealed mesangial deposits, indicating that the deposition of immune complexes in the mesangium occurs with highly anionic immune complexes. Cationic human serum albumin (AgED, isoelectric point 7.5 to 9.0) alone or as performed immune complexes ( AgEDAb ) showed rapid blood clearance (less than 1% remaining by 18 hours) and localized in renal glomeruli by immunofluorescence microscopy. AgED injected alone was present in glomeruli at 1 minute after injection but was absent at 12 hours. After injection of AgEDAb , both antigen and antibodies were present in glomeruli from 1 minute through 72 hours by immunofluorescence microscopy. Electron-dense deposits were seen at the anionic sites in the lamina rara interna and lamina rara externa at 1 minute and 1 hour after injection of AgED and AgEDAb containing free AgED. After AgEDAb injection electron-dense deposits were evident at 12 to 48 hours in the mesangium and in the subendothelial area, especially adjacent to the mesangium. By 72 hours after AgEDAb injections mesangial deposits predominated, although small subepithelial deposits were also present. An inflammatory reaction was noted in the glomeruli after administration of AgEDAb . Thus, preformed immune complexes containing cationized antigen show glomerular deposition, primarily in the subendothelial and mesangial regions and at later time points also in the subepithelial area.