Electron microscopic studies of human glomerulonephritis with ferritin-conjugated antibody. Localization of antigen-antibody complexes in glomerular structures of patients with acute glomerulonephritis.

1. Kidney biopsies from 4 cases of severe acute glomerulonephritis were obtained 11 to 25 days after the onset of clinical manifestations of the disease. These tissues were treated with ferritin-conjugated antibodies to 7S gamma-globulin, beta(1C), and Type 12 streptococcal products. Adjacent pieces of the biopsied material were treated with control ferritin-labeled antisera or with ferritin alone. As further controls, normal renal tissue and renal tissue from patients with other kidney diseases were treated with the same antisera. The 3 antisera to 7S gamma-globulin, beta(1C) and Type 12 streptococcus were specifically bound in electron-opaque foreign material in the following renal areas: (a) the lumen of glomerular capillaries; (b) medullary arteriolar walls (2 cases); (c) pinocytic vacuoles and absorption droplets of endothelial or mesangial cells; (d) canals between proliferating mesangial or endothelial cells which connect the capillary lumen with the deep mesangial region or with the endothelial side of the basement membrane; (e) basement membrane proper; (f) subendothelial and certain subepithelial deposits; and (g) Bowman's space. 2. None of the 3 ferritin-conjugated antisera listed above were bound to the nuclei of glomerular cells or to portions of the cytoplasm other than those specified. 3. Ferritin-conjugated antisera to pneumococcus Type II and vaccinia virus and ferritin alone were not bound to any structures in the glomerular tissue. 4. None of the ferritin-conjugated antisera bound to normal renal tissue or to kidney tissue from other renal disease. 5. The data obtained are compatible with the following working hypothesis: Antigen-antibody aggregates of Type 12 streptococcal products, gamma-globulin, and complement are present in the circulating blood of patients with severe acute glomerulonephritis. Large amounts of the complexes are caught in the filtering system of the glomeruli. The inflammatory reactions seen in the glomerular structures result from the presence of the immune complexes and of the polymorphonuclear leukocytes which conjointly may be responsible for the disease.