Neoantigens and antibodies to factor VIII.

It is well known that 10-20% of severe haemophiliacs are likely to develop inhibitors to factor VIII, usually soon after the commencement of therapy. Two recent inhibitor outbreaks have occurred in patients treated for a number of years on switching to a product subjected to additional virus inactivation. Hence the incidence of inhibitor formation may be affected by the type of product used for treatment and the potential for processing to result in 'neoantigens'. Examination of the parts of factor VIII interacting with inhibiting antibodies, and the effect of various therapies on these, can teach us something about the mechanisms involved in antibody formation. However, the development of pre-clinical assays to assess products and processes for neoantigen formation should allow the prevention of inhibitor outbreaks. This review summarizes current in vitro and in vivo approaches to this problem, concluding that most available assays are inadequate for this purpose, with competitive immunoassay and phospholipid binding providing the most hopeful route forward.