THE NATURAL-HISTORY OF THE IMMUNE-RESPONSE TO EXOGENOUS FACTOR-VIII IN SEVERE HEMOPHILIA-A

The development of inhibitory antibodies to factor VIII (fVIII) in sev ere haemophilia A patients is a serious therapeutic complication. Usin g a highly sensitive immunoprecipitation (IP) assay which measures all anti-fVIII antibodies, we have tested severe haemophilic plasmas from two clinical studies. Inhibitor titres in the range of 0.4 to 1 Bethe sda units/ml (BU/ml) could not be verified by IP as being due to an im mune response to Nm in 35% of plasmas tested. Low fVIII recoveries wer e likewise correlated with the presence of antibodies in 29% of plasma s tested, However, 16% of plasmas without inhibitor titres had immune responses as measured by IF. The rapidity of antibody appearance did n ot allow their effective detection by LP before development of inhibit or titres. These results suggest that the LP assay can provide a valua ble confirmation of anti-fVIII antibody production when the Bethesda a ssay is low or negative and where clinical observations suggest their presence, but they cannot be used reliably to detect early immune resp onses.