STUDY OF THE IDIOTYPIC RESPONSE TO AUTOANTIBODY TO THE ALTERNATIVE PATHWAY C3/C5 CONVERTASE IN NORMAL INDIVIDUALS, PATIENTS WITH MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS, AND EXPERIMENTAL-ANIMALS

We studied the fluctuation of autoantibody to the alternative pathway C3 C5 convertase (C3NeF) and its autoantiidiotypic antibodies, Ab2α and Ab2β, in normal individuals, patients with membranoproliferative glomerulonephritis (MPGN), and New Zealand white rabbits. In normal individuals, serum levels of Ab2α (anti-id Ab without internal imagery to the native antigen) are several times higher than those for Ab2β (anti-id Ab bearing the internal image of the native antigen). When normal rabbits are immunized with Ab2β, Ab3 is produced which has strong C3NeF activity. Ab3 acts to stimulate the prompt production of Ab4α. Ab3 (C3NeF) titers then fall, followed by the appearance of Ab4β. Patients with MPGN and C3NeF activity were also studied. Untreated patients at the time of diagnosis have a two- to fourfold predominance of Ab2β which is a direct reversal of the normal situation. When the patients were treated with prednisone, C3NeF levels fell and Ab2α again predominated. These data suggest that the idiotypic network acts to control the production of autoantibody in a balanced fashion. Moreover, these data suggest that the patients' response to Ab1 is quite different than that found in normal individuals. © 1992.