Differential capacity of anti-RAP and anti-megalin antibodies to produce progressive passive Heymann nephritis - implications for the pathogenesis of idiopathic human membranous glomerulonephritis.
Passive Heymann nephritis (PHN) induced with heterologous antisera has been described according to various criteria, which may or may not include induction of chronic disease and proteinuria. Characteristics of the glomerular immune deposits determined by the antigenic specificities of the antisera presumably account for differences in disease outcome. In this study, the clinical and immunohistological features in the model produced with monospecific antisera were compared against megalin or receptor associated protein (RAP), two proteins that have been implicated as target antigens in PHN. Rats injected with either anti-megalin or anti-RAP antiserum developed typical glomerular immune deposits of PHN when examined after 7 days. Although the deposits stained for complement, none of the animals had abnormal proteinuria in this time frame. Over a longer time course (7-16 weeks), immune deposits persisted and proteinuria increased to pathological levels in all animals injected with anti-megalin serum. By contrast, immune deposits had cleared from the kidneys of rats injected with anti-RAP antiserum when examined at 7-8 weeks post-injection and the proteinuria levels observed up to 13 weeks remained in the normal range. Additional doses of anti-RAP antiserum given 4 and 17 days after the first injection did not prolong the duration of glomerular immune deposits. These results demonstrate a clear divergence in pathogenic potential of antisera generated against the two renal antigens, which suggest differences in the immune deposits linked to a soluble antigen that is non-covalently bound to the podocyte membrane versus those linked to an integral membrane antigen. These observations could provide clues to the nature of the unknown glomerular autoantigen of idiopathic membranous glomerulonephritis in humans.
Makker
S P
SP
Department of Pediatrics, University of California, Davis, School of Medicine, One Shields Avenue, CA 95616, USA. spmakker@ucdavis.edu
Tramontano
A
A
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D003176:Complement C3 / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000276:immunology* / Q000473:pathology; D026541:Heymann Nephritis Antigenic Complex / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000276:immunology; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D011507:Proteinuria / Q000276:immunology / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D003176:Complement C3; D026541:Heymann Nephritis Antigenic Complex; D007074:Immunoglobulin G; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D003165:Complement System Proteins