Antigen as mediator of glomerular injury in experimental IgA nephropathy.
IgA immune complexes (IgA-IC) are considered the primary cause of IgA nephropathy. Despite the consistent findings of IgA and frequently C3 glomerular deposits in most patients, the renal histopathologic lesion may vary from mild mesangial involvement to severe sclerosis. In the IgA immune deposits, IgA and C3 are considered to be relatively constant, whereas the composition of the antigen is expected to vary according to its origin. This report explored th possibility that the histopathologic lesion is a function of the antigen in an IgA immune deposit. To test this hypothesis we developed a passive model of IgA nephropathy whereby glomerular IgA deposits can capture, in situ, circulating antigens. In this model, glomerular IgA deposits (IgA/IgA-IC) were induced by administration of a constant amount of IgA anti-dinitrophenyl (antibody) and dinitrophenyl-conjugated IgA anti-phosphorylcholine (PC) as an antigen. The latter also served as antibody to capture, in situ, circulating PC-containing antigens. Mice that received only IgA/IgA-IC developed glomerular IgA and C3 deposits and a focal increase in mesangial cells and matrix, but no evidence of renal damage. A diffuse increase in mesangial cells and matrix developed in mice treated with IgA/IgA-IC and either PC-Ficoll (carbohydrate antigen) or PC conjugate of bovine serum albumin (protein antigen). In contrast, mice that received IgA/IgA-IC and pneumococcal C polysaccharide, a PC-containing antigen, developed severe diffuse mesangial hypercellularity with segmental necrosis and thrombosis. These mice also developed proteinuria and hematuria. Our results demonstrate that the antigen plays a critical role in development of glomerulonephritis associated with IgA-IC.
Montinaro
V
V
Department of Pathology, Rhode Island Hospital, Providence.
Esparza
A R
AR
Cavallo
T
T
Rifai
A
A
D000818:Animals; D000936:Antigen-Antibody Complex / Q000032:analysis*; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D003176:Complement C3 / Q000032:analysis; D005260:Female; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000473:pathology*; D007070:Immunoglobulin A / Q000032:analysis* / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology*
D000936:Antigen-Antibody Complex; D000942:Antigens, Bacterial; D003176:Complement C3; D007070:Immunoglobulin A; D011135:Polysaccharides, Bacterial; C027158:polysaccharide C-substance (Streptococcus)