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.