Pathogenesis of IgA Immune Complex-Mediated Glomerulonephritis

Abstract

In a period of less than ten years, complementary experimental and clinical observations have contributed greatly to our understanding of various aspects of IgA immune complexes and their pathogenetic potential in IgA nephropathy. The primary mechanism of glomerular IgA deposition has been discussed in the light of experimental data. These findings indicate that the molecular form of IgA is critical for the formation of large- and intermediate-sized complexes that result in glomerular deposition. Glomerular IgA deposits, however, appear to develop in a continuum of preformed polymeric IgA complexes and in situ formed monomeric IgA complexes. Removal of IgA immune complexes from the circulation is mediated by the liver, with no evidence of any removal dysfunction in IgA nephropathy patients. IgA macromolecules are unable to activate the complement pathway in vitro or as a glomerular deposit. Complement activation, however, is shown to be an antigen-mediated process. Participation of the complement system in induction of glomerular injury associated with IgA nephropathy needs further investigation. Experimental evidence supports the hypothesis that in IgA immune complex-mediated nephropathy, the repertoire of IgA immune complexes that induce mesangial proliferation and glomerular sclerosis consists of IgA-bound nephritogenic antigens which determine the extent and outcome of glomerular injury.