Kinetics and fate of IgA-IgG aggregates as a model of naturally occurring immune complexes in IgA nephropathy.

ABSTRACT

The characteristic granular IgA immunofluorescent pattern in the kidneys of IgA nephropathy patients is consistent with immune complex pathogenesis. The possibility of a delayed clearance of IgA-containing immune complexes from circulation in IgA nephropathy patients is still under discussion. Since pure IgA immune complexes are probably nonphlogistic, (in contrast to IgG-containing IgA immune complexes), the in vivo clearance of a mixture of heat-aggregated IgA/G purified from pooled human sera was analyzed. The test probe was efficiently labeled with 123I and the time course of radioactivity was measured by a gamma-camera. Both the liver and the spleen were found to be involved in the disappearance of IgA/G complexes. Liver accumulation, which was markedly predominant, closely approximates a gamma-variate function which allowed determination of a mean transit time of 34.37 minutes, range 29.8 to 42.2, in 8 normal and 37.54 minutes, range 30.9 to 50.7 in 17 patients (p less than 0.04). At 2 hours, segmental gut accumulation was found, which demonstrated removal by hepatobiliary system as well. Compartmental analysis in patients indicated 3 major compartments represented by vascular bed, hepatobiliary and reticuloendothelial systems (including both liver and spleen phagocytes). Blood clearance rate, representing the final result of multiorgan removal of the test probe from the blood stream, was found to be significantly delayed in IgA nephropathy patients with a slope (0.035 min-1, range 0.019 to 0.052) significantly less negative compared with controls (0.047 min-1, range 0.038 to 0.053, p less than 0.01). This test probe was able to reproduce both removal routes (macrophages cells and hepatobiliary system) hypothesized for IgA-containing immune complexes in humans.