Membranoproliferative glomerulonephritis. Localization of early components of complement in glomerular deposits.
A body of evidence suggests that in membranoproliferative glomerulonephritis (MPGN), complement is activated by the alternate pathway. Therefore, deposition of early components of complement should not be expected in glomeruli. The renal tissues of 16 patients--13 with classic MPGN and 3 with dense deposit disease, a variant of MPGN--were studied by light and electron microscopy and by means of elution and immunofluorescence for the localization of complement (C1q, C4, and C3), immunoglobulins (1gG, IgM, and 1gA), and other serum proteins. Variable amounts of C3, C4 and/or C1q, and IgM were detected in the glomeruli of all patients, whereas IgG and IgA were present, respectively, in 15 of 16 and 6 of 16 patients. Deposits were localized in mesangium and in peripheral capillary loops in a typical lobular distribution. The specificity of each antiserum was verified by immunodiffusion, immunoelectrophoresis, and blocking experiments utilizing unlabeled antibody. Glomerular-bound IgG was eluted with acid citrate buffer, suggesting that IgG might be complexed with antigen(s) in glomerular deposits. By light microscopy, lesions ranged from focal proliferation and lobulation to more severe involvement with typical splitting of glomerular basement membranes, sclerosis, and less frequently, crescent formation. Ultrastructurally, all patients with classic MPGN exhibited mesangial and subendothelial deposits, and in 5 of these patients, subepithelial deposits were demonstrated. With the exception of ultrastructural lesions, patients with the dense deposit variant lacked distinguishable features when compared with those with classic MPGN. The significance of these findings is discussed in relation to a) activation of complement and the possible role of an immune complex mechanism and b) the variability of the morphologic expression.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000032:analysis; D001485:Basement Membrane / Q000276:immunology; D001666:Binding Sites, Antibody; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis*; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007105:Immune Complex Diseases / Q000276:immunology; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007678:Kidney Glomerulus / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged
D000936:Antigen-Antibody Complex; D003176:Complement C3; D003181:Complement C4; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D003165:Complement System Proteins