Analysis of glomeruli-eluted Gp330 autoantibodies and of Gp330 antigen of Heymann nephritis.

UNLABELLED

Quantity, charge, IgG isotype, Ag reactivity of glomerular gp330 autoantibodies (gp330Ab), and the charge of the putative Ag, gp330, were studied in active Heymann nephritis. Gp330 was anionic with an isoelectric point of 4.6. Despite variation in C3 glomerular immunofluorescence staining, C5b-9 staining was seen in all rats. Positive correlation was seen between glomerular gp330Ab and abnormal 24-h proteinuria (r = 0.637, p = 0.008), which appeared to require a certain threshold level of gp330Ab. Positive correlation was also seen between serum and glomerular gp330Ab at time of death (r = 0.55, p < 0.05). No differences were seen in charge, IgG isotypes of glomerular gp330Ab, or reactivity to gp330 by Western analysis in rats with or without abnormal proteinuria. Comparison of gp330Ab IgG isotypes in immune sera and glomeruli showed no difference in IgG1 and IgG2a, but IgG2b was significantly lower in glomeruli (p < 0.0001).

CONCLUSIONS

1. this is the first documentation that gp330 is highly anionic; 2) regardless of the degree of proteinuria, all immunized rats deposit in their glomeruli a qualitatively similar type of gp330Ab (charge, IgG isotype, complement activation, gp330 reactivity); 3) despite the highly anionic nature of gp330, anionic gp330Ab accumulate in glomeruli; and 4) complement activation appears to occur in every rat with gp330Ab in glomerulus and development of proteinuria is dependent on a certain threshold level of gp330Ab in the glomerulus which, in turn, correlates with the serum level of gp330Ab.