Cellular Reactivity to Altered Glomerular Basement Membrane in Glomerulonephritis

Glomerular basement membrane may be altered during glomerulonephritis, exposing antigens that are recognized as foreign. Immunochemical studies suggest that removal of peripheral glycopeptides from the basement membrane with glycosidase mimics this pathogenetic event. To examine these hypotheses, we studied 24 patients with biopsy-proved glomerulonephritis by means of the lymphocyte-blast-transformation assay. Three preparations of normal glomerular basement membrane were used: two mimicked the native state for the peripheral glycopeptides, and one was altered by glycosidases. Results showed minimal differences in responses to native glomerular basement-membrane preparations among patients with glomerulonephritis and control groups. However, patients with glomerulonephritis had a significant blastogenic response to the glycosidase-treated glomerular basement membrane as compared to patients with nonglomerular renal disease and normal controls (P<0.0005). These studies suggest that cellular reactivity to altered glomerular basement-membrane antigens can be detected in certain forms of progressive glomerulonephritis. (N Engl J Med 298:861–868, 1978) A NUMBER of investigators have shown that the deposition of immune complexes along the glomerular basement membrane is associated with physical and immunochemical alteration of the glomerular basement membrane.^1,2 It is believed that this alteration may be mediated via the release of lysosomal enzymes by phagocytic cells during phagocytosis of immune complexes.^3,4 Both urinary proteases in animals¹ and urinary glycosidases in man⁵ have been shown to be elevated during acute glomerulonephritis. These observations have suggested that altered glomerular basement-membrane antigens exposed during the immunopathogenesis of glomerulonephritis might be recognized by the host as foreign and provide the stimulus for continued.