The pathogenesis of experimental membranous glomerulonephritis induced with homologous nephritogenic tubular antigen.

Abstract

The renal tubular epithelial antigen (Tub-Ag) of rats was solublized by Pronase and purified by gel filtration and acrylamide gel electrophoresis. Purified Tub-Ag was a glycoprotein with S20,W value of 8.4. Utilizing radiolabeled Tug-Ag, a sensitive radioimmunoassay for Tub-Ag and homologous antibody (anti-Tub-Ag) was developed. Tub-Ag activity associated with a protein of the same molecular size was demonstrated in the serum, as well as in Pronase extracts of all the organs tested, including kidney, liver, lung, spleen, intestine, stomach, and heart. The physiochemical properties of the Tub-Ag of rats and its distribution were essentially the same as the Tub-Ag of humans, which had been found in immune deposits in the kidney of some patients with idiopathic membranous glomerulonephritis. Rats were immunized with the purified Tub-Ag emulsified in Freund's complete adjuvant and followed for Tub-Ag and anti-Tub-Ag in the serum, as well as for proteinuria and immunohistological changes in the kidney. Serum Tub-Ag dropped sharply after 20 days, when anti-Tub-Ag appeared in the circulation. Persistent, massive proteinuria appeared still later, more than 30 days after injection, when anti-Tub-Ag disappeared and Tub-Ag reappeared in the serum of some of those rats. In others, anti-Tub-Ag in the serum persisted throughout the observation period of 90 days. The pathology of the kidney of the rats with proteinuria was that of a typical membranous glomerulonephritis; thickening of glomerular capillary walls with granular deposits of gamma-globulin and Tub-Ag was observed. On the basis of these results, Tub-Ag in the serum, probably released from cellular membranes of various organs as a physiological metabolite, is considered to maintain the pathological process in the kidney by providing the antigen continuously to form immune complexes.