Avidity of anti-glomerular basement membrane autoantibodies was associated with disease severity

Anti-glomerular basement membrane (GBM) antibody-mediated diseases are characterized by the binding of autoantibodies to GBM, leading to rapidly progressive glomerulonephritis that often results in irreversible loss of renal function. The nephrotoxic potential of anti-GBM antibodies has been demonstrated in animal experiments. We questioned whether high avidity leads to persistent deposition of antiGBM antibodies, thereby perpetuating inflammation and renal damage. To address the hypothesis, sera from 32 patients and serial samples from 11 patients with anti-GBM disease were collected. Purified bovine a chain non-collagen I domains of type IV collagen [alpha(IV)NC1] were employed to exam avidity of anti-GBM antibodies using antigen-inhibition enzyme-linked immunosorbent assay. The amount of alpha(IV)NC1 needed for 50% inhibition of antibody binding was compared among patients with different clinical and pathological parameters. After the sera were diluted to give equivalent concentration of anti-GBM antibodies, the amount of alpha(IV)NC1 used for 50% inhibition was prominently different among patients, from 0.02 mu g to 20 mu g, with an average at 0.666 mu g. A significant correlation was observed between the amount of alpha(IV)NC1 used and the percentage of glomeruli which had crescents (P = 0.001). Higher avidity of anti-GBM antibodies predicted higher percentage of glomerular crescents (R-2 = 0.58, P < 0.001). No obvious change of avidity was observed in the serial samples. The results suggested that affinity maturation might have been completed by the time that patients presented with anti-GBM disease. The avidity of anti-GBM antibodies was associated with the degree of renal damage and might play a key role in the pathogenesis of anti-GBM disease. (c) 2005 Elsevier Inc. All rights reserved.