Anti-idiotypes to factor VIII antibodies and their possible role in the pathogenesis and treatment of factor VIII inhibitors.

Studies on the production and characterization of anti-idiotype antibodies (AId) to monoclonal factor VIII antibodies (McFVIIIAb) are reported. Two AIds were produced and one of these exhibited cross-reactivity with two other McFVIIIAb but showed no reactivity with haemophilic and non-haemophilic FVIIIAb. This AId was also active against McFVIIIAb which bound immunologically active forms of factor VIII but it did not neutralize McFVIIIAb directed against procoagulant factor VIII. The in vitro effect of therapeutic pooled human IgG concentrates upon haemophilic and non-haemophilic FVIIIAb was also assessed. Approximately 25% of non-haemophilic FVIIIAb were inhibited following incubation with human IgG whereas the latter had no effect upon haemophilic FVIIIAb activity. Studies on haemophilic sibling pairs of FVIIIAb and non-FVIIIAb producing individuals indicated FVIIIAb neutralizing activity in the non-FVIIIAb producing sibling's IgG fraction which may be of anti-idiotypic origin. These findings lend further support to suggestions that anti-idiotypes have a regulatory role in FVIIIAb production and are of potential therapeutic value.