Anti-idiotypic suppression of autoantibodies to factor VIII (antihaemophilic factor) by high-dose intravenous gammaglobulin.
In two patients with high-titre autoantibodies to antihaemophilic factor (VIIIc), treatment with high-dose intravenous immunoglobulin (IVIg) resulted in rapid and prolonged, although not total, suppression of antibody. IVIg also inhibited anti-VIIIc activity in patients' plasma in vitro; IVIg and F(ab')2 fragments from IVIg inhibited anti-VIIIc activity of the IgG fraction and of the Fab'2 fragments of the IgG fraction from patients' plasma, indicating that the in-vivo effect of IVIg was due to the presence in the therapeutic immunoglobulins of anti-idiotypic antibodies against idiotypes expressed by anti-VIIIc autoantibodies. In contrast, IVIg had little or no effect on antibody titre in two haemophilic patients with anti-VIIIc alloantibodies. These observations suggest that IVIg contains anti-idiotypes against autoantibodies and may be effective in the treatment of some autoimmune diseases through idiotypic/anti-idiotypic interactions.
D000293:Adolescent; D000328:Adult; D000941:Antigens / Q000032:analysis*; D001323:Autoantibodies / Q000096:biosynthesis*; D005169:Factor VIII / Q000032:analysis / Q000276:immunology*; D005260:Female; D006467:Hemophilia A / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000627:therapeutic use; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D016756:Immunoglobulins, Intravenous; D007263:Infusions, Parenteral; D007518:Isoantibodies / Q000032:analysis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology; D011863:Radioimmunoassay
D000941:Antigens; D001323:Autoantibodies; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D005169:Factor VIII