Jean Guy Gilles

Anti–Idiotypic Antibodies: From Regulation to Therapy of Factor VIII Inhibitors

Evidence has recently accumulated showing that anti–idiotypic antibodies specific to anti–FVIII antibodies are present in the plasma of healthy individuals and of haemophilia A patients with or without inhibitors, where they can neutralise the FVIII inhibitory activity. Additionally, patients successfully desensitised towards FVIII have an increased production of anti–idiotypic antibodies with no significant reduction in anti–FVIII antibodies. We review here possible strategies for modulating the anti–FVIII immune response by idiotypic interactions.

Heating Lyophilised Factor VIII Does Not Alter Its Recognition by Specific Antibodies

Background and objectives: Alterations of factor VIII (FVIII) during preparation procedures can potentially affect its immunogenicity. One method evaluating such alterations could be by determining the reactivity of FVIII with specific antibodies. Materials and methods: Since heat treatment is currently used to reduce the risk of viral transmission, we evaluated the immunoreactivity of plasma‐derived FVIII before and after heating at different temperatures and for different periods. Freeze‐dried FVIII was used for these experiments as part of the validation procedure of a novel FVIII preparation. Results: Heating FVIII for up to 72 h at 80 °C does not alter its reactivity with specific rabbit antibodies or mouse monoclonal antibodies, although some loss of FVIII activity occurred after 72 h. After heating for 2 h at 100 °C, a procedure that reduced FVIII activity by about 50%, there were still no significant effects on FVIII reactivity with monoclonal antibodies. Conclusions: Freeze‐dried preparations of plasma‐derived FVIII seem to be resistant to heat‐induced structural denaturation.

Coagulation Factor VIII autoantibodies

Publisher Summary This chapter focuses on coagulation factor VIII (FVIII) autoantibodies. FVIII is obtained from multidonor plasma pools by cryoprecipitation followed by removal of contaminant proteins, including filtration, chromatography on ion-exchangers, or affinity sorbents and immunoaffinity. Testing for autoantibodies towards FVIII should be carried out in cases in which an unexpectedly prolonged coagulation time is observed, even in the absence of overt associated diseases or predisposing conditions such as the postpartum period. The assay systems in which the neutralizing effect of antibodies on the procoagulant activity of FVIII is determined are simple to use and provide reliable results.

COAGULATION FACTOR AUTOANTIBODIES

ABSTRACT Autoantibodies (AAbs) that interfere with coagulation factors are rare events. They usually inhibit the function of the target molecule in the coagulation pathway, which consists of a cascade of proteolytic reactions in which inactive circulating proteins are converted into active serine proteases to finally form a fibrin clot. A cartoon of general organization of the coagulation is presented to help clinicians and clinical investigators to localize the different steps at which Abs may inhibit the coagulation cascade and thereby, in association with clinical manifestations and laboratory assays, to facilitate an early diagnosis. The presence of Abs results primarily in bleeding disorders, which can be acute and life-threatening in some cases. Clinical manifestations can also be progressive, with formation of haematomas in various organs. AAbs appear spontaneously in the context of systemic autoimmune diseases, in association with drug intake, after surgery or in postpartum period, but also after exposure to a cross-reactive antigen. Due to their frequency, a special emphasis is put on for AAbs to coagulation factor VIII (FVIII) and its chaperon molecule von Willebrand factor. Treatment as proposed in the literature is described.