Experimental IgA nephropathy.
An animal model for IgA immune complex nephritis was developed. IgA immune complexes formed in vitro with an IgA anti-dinitrophenyl (DNP) derived from MOPC-315 plasmacytoma, and dinitrophenylated bovine serum albumin (DNP-BSA) produced mild focal glomerulonephritis in mice. Similar, but more severe pathological changes were produced with complexes formed in vivo either in normal mice or MOPC-315 tumor-bearing mice. In contrast to the focal nature of the PAS-positive glomerular lesions observed by light microscopy, immunofluorescent examination revealed IgA deposits in all glomeruli. This discrepancy between immunofluorescent and histopathologic findings as well as the distribution of the immune complexes within the affected glomeruli, are some of the features which bear resemblance between this experimental model and human IgA nephropathy. Fixation of complements by DNP-BSA-IgA immune complexes, formed in vitro or in vivo, was shown to occur in the glomeruli of mice with IgA immune complex nephropathy. The pattern of C3 glomerular deposits was similar to that of IgA. However, complement proved to be nonessential for complex deposition. This conclusion is based on the observation that decomplemented mice, although showing no deposition of C3 in their glomerulus, developed glomerular immunohistological changes similar to those observed in experimental mice that were not decomplemented. Polymeric IgA was observed to be critical for renal deposition of complexes and induction of nephritic histological changes. In contrast, monomeric IgA immune complexes failed to produce glomerular deposits. This finding raises the possibility that secretory IgA, which is predominantly polymeric, may play a role in human IgA-associated glomerulonephritis.
D000818:Animals; D000906:Antibodies; D000936:Antigen-Antibody Complex; D000941:Antigens; D003176:Complement C3 / Q000276:immunology; D004136:Dinitrobenzenes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology*; D007105:Immune Complex Diseases / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D009194:Myeloma Proteins / Q000276:immunology
D000906:Antibodies; D000936:Antigen-Antibody Complex; D000941:Antigens; D003176:Complement C3; D004136:Dinitrobenzenes; D007070:Immunoglobulin A; D009194:Myeloma Proteins