An active model of immune complex glomerulonephritis in the rat employing cationized antigen

Abstract

An active model of in situ immune complex glomerulonephritis involving a cationic antigen was established. Three weeks after immunization with human IgG, the left kidneys of Wistar rats were perfused with 100 micrograms of cationized human IgG (pI greater than 9.5) via the left renal artery. At this time the animals exhibited a mean serum concentration of 0.58 +/- 0.33 mg anti-human IgG antibody per milliliter. Renal tissue was examined at regular intervals by immunofluorescence, light, and electron microscopy thereafter. Cationized human IgG and rat IgG were distributed along the glomerular capillary wall in a pattern that became increasingly granular with time; rat C3 was also present. Histologically, a severe proliferative lesion was seen with crescent formation in 10-20% of the glomeruli; adhesions of glomerular tufts to Bowman's capsule were common and with time spike formation in the glomerular basement membrane became very prominent. Extensive subepithelial dense deposits were seen by electron microscopy. Proteinuria was present in 19 of 26 animals within 24 hours, and in 30 of 31 by Day 7. Protein excretion fell from Day 14 onward, but some animals exhibited chronic proteinuria. The model described here represents another situation in which cationic antigens can induce subepithelial immune complexes, namely, the rapid release of small quantities of antigen into a previously sensitized host. This sequence could well mirror the events occurring in nature more closely than the previously described passive in situ model.