Characterization of human anti-glomerular basement membrane antibodies eluted from glomerulonephritic kidneys

Abstract

Eluates from glomerulonephritic kidneys of nine patients with anti-glomerular basement membrane (anti-GBM)-mediated nephritis were studied to define their antigenic specificity and content of kidney-fixing antibodies. Five of these patients had Goodpasture's syndrome with pulmonary and renal involvement clinically; four patients did not. All had in vivo fixation of IgG in the characteristic linear pattern by direct immunofluorescence, and eluted IgG fixed to normal human kidney sections. Eluates from kidneys of patients with Goodpasture's syndrome fixed more frequently to homologous nonglomerular renal and extrarenal antigenic sites and to heterologous GBM than did non-Goodpasture eluates over a hundredfold range of antibody concentrations; both could be blocked by prior absorption with soluble GBM antigens. By radial immunodiffusion and precipitation tests the content of IgG in the eluates was measured to range from 2 to 20% of the total protein eluted. By paired label isotopic fixation studies with some of the eluates the per cent of IgG that was kidney fixing ranged from 0.6 to 23.4%. Although the in vivo fixation studies with radiolabeled eluates failed to indicate significant fixation to monkey lung, the observations define quantitative as well as qualitative differences between anti-GBM antibody populations mediating the Good-pasture syndrome compared to those causing glomerulonephritis without lung involvement.