Deposition of Renal Tubular Epithelial Antigen Along the Glomerular Capillary Walls of Patients with Membranous Glomerulonephritis

Abstract

Abstract Membranous glomerulonephritis (Mb-GN)1 is a primary renal disease in which immunologically characteristic alteration of the glomerular capillary walls, namely the uniform granular deposition of γ- and β1c-globulins along the glomerular capillary walls, is found. This characteristic immunopathologic finding also has been induced experimentally in animals by the injection of various heterologous antigens and, recently, by the injection of homologous renal tubular epithelial antigen (Tub-Ag) (1). The pathogenesis of these experimental glomerulonephrides, especially the participation of antigen-antibody complexes, has already been well clarified (2, 3). In human Mb-GN, most investigators are inclined to accept the same immunologic mechanism for the development of the disease. But the antigens which compose the glomerular immune deposits in human idiopathic Mb-GN have not been identified. We have demonstrated with immunofluorescent technique the deposition of Tub-Ag along the glomerular capillary walls of three patients with Mb-GN. Human Tub-Ag was prepared from autopsied kidneys by the method of Edgington, Glassock, and Dixon (1). Three albino rabbits were immunized first with a footpad injection of 10 mg of the antigen in incomplete Freund's adjuvant, followed by a booster injection of 3 mg of the same antigen, subcutaneously, after 4 weeks. Ten days after the last injection the animals were bled and the sera were collected. The antisera were absorbed with normal human serum and a γ-globulin fraction was prepared by the 33% ammonium sulfate precipitation method. It was then conjugated with fluorescein isothiocyanate (FITC). This reagent stained specifically the luminal layer of proximal tubules in the cryostat sections of normal kidneys. Fluorescinated antisera against serum components were obtained from Behringwerke (Marburg-Lahn, West Germany).