Passive Heymann nephritis induced by genetic immunization using megalin cDNA fragments

Objectives: Heymann nephritis is a rat experimental model of membranous glomerulonephritis. Megalin has been cloned as an authentic pathogenic antigen for Heymann nephritis. In the present study, we aimed to establish passive Heymann nephritis using genetic immunization. Methods: Three different rabbit anti-rat megalin antibodies were produced by genetic immunization with rat megalin cDNA encoding amino acids 1-236 (L1-6), 1-156 (L1-4), or 157-236 (L5-6). Purified rabbit IgG was injected into the tail artery of Lewis rats. Results: Three of 6 rats in the L1-6 group and 1 of 9 rats in the L5-6 group injected with rabbit IgG showed significant proteinuria on day 21. The remaining 22 rats had no significant proteinuria. In the kidneys, on day 21 after IgG injection, binding of rabbit IgG to rat glomeruli was not observed among the groups. Rat IgG binding to rat glomeruli was observed in only 4 rats with significant proteinuria. Glomerular subepithelial electron dense deposits consistent with Heymann nephritis were found in only 4 rats with significant proteinuria. Conclusions: This is the first report of passive Heymann nephritis induced by genetic immunization with megalin cDNA fragments. Further investigation is needed to establish whether or not there is an increase in the incidence of disease by genetic immunization.