MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS - LOCALIZATION OF EARLY COMPONENTS OF COMPLEMENT IN GLOMERULAR DEPOSITS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 84  (2) , 283-298
Abstract
In membranoproliferative glomerulonephritis (MPGN), complement [C] probably is activated by the alternate pathway. Thus, deposition of early components of C 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 C (Clq [q fragment of the 1st C component], C4, and C3), immunoglobulin G (IgG), IgM, and IgA and other serum proteins. Variable amounts of C3, C4 and/or Clq, 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 activation of C and the possible role of an immune complex mechanism and the variability of the morphologic expression.