Glomerulonephritis with organized deposits: a mesangiopathic, not immune complex-mediated disease? A pathologic study of two cases in the same family.
Similar glomerular changes (marked widening of the mesangial stalk, irregular basement membrane thickening, and presence of mesangial and subendothelial deposits) were observed by light microscopy in renal biopsy specimens from two patients (mother and daughter) affected by nephrotic syndrome. Electron microscopy disclosed huge glomerular electron-dense deposits containing 12-nm fibrils in both patients. Immunohistochemical investigations performed with antisera anti-immunoglobulin (Ig) and anti-complement fractions, anti-laminin, anti-collagen IV, and anti-fibronectin (FN) showed scant and focal Ig and complement deposits and strong deposits of FN in the mesangium and along glomerular basement membranes. Most glomerular FN was plasma-derived, as shown by immunohistochemical tests with monoclonal antibodies specific for both plasma and cell-derived FN (IST-4) and for cell-derived FN (IST-9). Electron-dense deposits with fibrillar component could hardly correspond to the Ig and complement deposits, whereas they could be related to FN deposits. Since it is known that in glomeruli FN binds to Ig and immune complexes, and the latter seem to be too scant to justify light and electron microscopic lesions and clinical findings, the hypothesis of a primary mesangiopathic glomerulonephritis in some way connected with abnormal plasma FN deposition within the glomeruli and subsequent non-specific immune reactant entrapment could be considered. We could be dealing with a peculiar form of fibrillary glomerulonephritis with rather indolent evolution, as shown by a slow decrease of glomerular function and the scarcely modified glomerular changes found in the second biopsy performed in the mother 8 years after the first investigation.
Mazzucco
G
G
Department of Biomedical Sciences and Human Oncology, University of Torino, Italy.
Maran
E
E
Rollino
C
C
Monga
G
G
D000293:Adolescent; D000328:Adult; D005260:Female; D005353:Fibronectins / Q000097:blood; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000648:ultrastructure*; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron
D005353:Fibronectins