Heymann nephritis in rats induced by human renal tubular antigens: characterization of antigen and antibody specificities.

An injection of human renal tubular fraction, Fx1A, with Freund's complete adjuvant in rats induces Heymann nephritis (HN) with clinical and morphological features similar to rat Fx1A-induced HN. The present study was undertaken to characterize antibody specificities and the corresponding antigen involved in human Fx1A-induced HN. In sera of rats immunized with human Fx1A, not only anti-human Fx1A antibody but also antirat Fx1A antibody was detected by enzyme immunoassay. Eluted antibody from the glomeruli also showed both activities. In an inhibition study of enzyme immunoassay, binding of the eluted antibody to human Fx1A was inhibited by both human and rat Fx1A and also by partially purified gp330, but not by purified gp108. Furthermore, binding of the eluted antibody to rat Fx1A was inhibited by both rat and human Fx1A. On immunoblot, the eluted antibody mainly reacted with a 440 kD glycoprotein of human Fx1A which showed the same mobility as rat gp330. The antibody also reacted with a band of gp330 of rat Fx1A. These results indicate that the 440 kD glycoprotein in humans is a counterpart of rat gp330 and that the eluted antibody has dual specificities to both human 440 kD glycoprotein and rat gp330, suggesting that the cross-reactive antibody is responsible for human Fx1A-induced HN.