Heymann nephritis induced by kidney brush border glycoproteins

Heymann nephritis developed in rats immunized with brush border membrane fractions isolated from rat kidney tubules. Glomerular autoantibodies eluted from cryostat sections of nephritic kidneys reacted in immunoelectron microscopy with the outer surface of isolated brush border membrane vesicles. This indicates that the autoantigens are plasma membrane components. To characterize further the chemical nature of the nephritogenic autoantigens, we treated the brush border membranes with trypsin and sodium deoxycholate, and the solubilized membranes were then fractionated by lectin affinity chromatography. The polypeptide composition of the fractions was analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The capacity of the membrane fractions to induce Heymann nephritis was assessed by observing the development of typical renal lesions, antibrush border autoantibodies, and proteinuria in rats immunized with these fractions. The results suggest that the nephritogenic autoantigen is an integral component of the brush border membrane of kidney proximal tubules and has an affinity for Lens culinaris agglutinin. This indicates that it is a glycoprotein and has mannosyl and/or glycosyl groups exposed in its oligosaccharide side chains.