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 autoantidiotypic antibodies, Ab2 alpha and Ab2 beta, in normal individuals, patients with membranoproliferative glomerulonephritis (MPGN), and New Zealand white rabbits. In normal individuals, serum levels of Ab2 alpha (anti-id Ab without internal imagery to the native antigen) are several times higher than those for Ab2 beta (anti-id Ab bearing the internal image of the native antigen). When normal rabbits are immunized with Ab2 beta, Ab3 is produced which has strong C3NeF activity. Ab3 acts to stimulate the prompt production of Ab4 alpha. Ab3 (C3NeF) titers then fall, followed by the appearance of Ab4 beta. Patients with MPGN and C3NeF activity were also studied. Untreated patients at the time of diagnosis have a two- to fourfold predominance of Ab2 beta which is a direct reversal of the normal situation. When the patients were treated with prednisone, C3NeF levels fell and Ab2 alpha 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.
Spitzer
R E
RE
Department of Pediatrics, SUNY Health Science Center, Syracuse 13210.
Stitzel
A E
AE
Tsokos
G C
GC
D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D003178:Complement C3 Nephritic Factor / Q000276:immunology; D050577:Complement C3-C5 Convertases / Q000276:immunology*; D015432:Glomerulonephritis, Membranoproliferative / Q000097:blood; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D003178:Complement C3 Nephritic Factor; D007130:Immunoglobulin Idiotypes; D050577:Complement C3-C5 Convertases