A novel autoantibody to plasminogen and its characterization in Heymann nephritis.
Heymann nephritis (HN) of rat is an experimental model of human membranous glomerulonephropathy (MGN). It is generally accepted that the glomerular lesion of HN results from the binding of antibodies (autoantibodies in active HN and heterologous antibodies in passive HN) to gp330, a receptor of the low-density lipoprotein receptor superfamily located on the glomerular epithelial cell. We have previously shown that plasminogen (plg) is a ligand for gp330. This report shows that in addition to antibodies to receptor, gp330, novel autoantibodies (Aab) to ligand, plg, also develop in the course of HN and accumulate selectively and in parallel with gp330 antibodies in the glomeruli of both active and passive HN. Aab to plg are present in serum and in immunoglobulin G (IgG) eluted from glomeruli of diseased animals with the concentration severalfold greater in glomerular IgG than in an equivalent amount of serum IgG. Characterization of the Aab to plg shows that they are directed against the conformational epitopes of plg with some of those epitopes being located in the lysine-binding domain of plg. Aab to plg develop without exogenous immunization with plg. In active HN Aab to ligand, plg, develop following immunization with its autologous receptor, gp330, and in passive HN they develop following administration of polyclonal antibody to the receptor. Although the mechanism of their induction is not known, their selective accumulation in glomeruli suggests a role in the development of the MGN lesions in both active and passive HN.
Department of Pediatric Nephrology, University of California, Davis 95817.
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Makker
D000818:Animals; D001323:Autoantibodies / Q000378:metabolism*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005921:Glomerulonephritis / Q000145:classification / Q000276:immunology*; D026541:Heymann Nephritis Antigenic Complex; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D010958:Plasminogen / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley
D001323:Autoantibodies; D026541:Heymann Nephritis Antigenic Complex; D008562:Membrane Glycoproteins; D010958:Plasminogen