LACK OF IMMUNE-RESPONSE TO MOUSE IGC IN PREVIOUSLY UNTREATED HEMOPHILIA-A AND HEMOPHILIA-B PATIENTS TREATED WITH MONOCLONAL-ANTIBODY PURIFIED FACTOR-VIII AND FACTOR-IX PREPARATIONS

Immunoaffinity purification of factor VIII and factor IX results in th e inclusion of trace quantities (less than or equal to 50 ng 100 IU-1) of mouse protein in the final product. It is possible that infusion o f extremely low levels of proteins might induce human antimouse antibo dy (HAMA) responses. To test this possibility, IgG, IgM and IgE antibo dies to mouse IgG were assessed in previously untreated haemophilia A and haemophilia B patients (n = 9 and n = 11, respectively) who receiv ed monoclonal antibody (MAb) purified factor VIII (Monoclate-P(R) Anti haemophilic Factor [Human] Centeon, King of Prussia, PA) or factor IX (Mononine(R) Coagulation Factor IX [Human] Centeon). HAMA were evaluat ed prior to and 2-42 months after initial treatment. IgE antibodies to mouse IgG were undetectable (<19 ng ML-1) at all time points. Antimou se IgG levels for Monoclate-P-treated patients averaged (mean+/-SD) 0. 40+/-0.18 mu g mL(-1) prior to treatment, and 0.64+/-0.43 mu g mL(-1) at the time of last observation (P > 0.05, not significant [n.s.]). Re spective values for antimouse IgM in these patients were 2.48+/-1.20 m u g mL(-1) and 2.85+/-1.63 mu g mL(-1) (P > 0.05, n.s.). Antimouse IgG levels for Mononine-treated patients averaged 0.48+/-0.52 mu g mL(-1) prior to treatment, and 0.66+/-0.59 mu g mL(-1) after 3 months of the rapy (P > 0.05, n.s.). Respective values for antimouse IgM in these pa tients were 1.94+/-1.52 mu g mL(-1) and 1.77+/-0.99 mu g mL(-1) (P > 0 .05, n.s.). Lack of immunogenicity of traces of mouse protein in these preparations is supported in that none of the patients assessed devel oped anaphylactoid reactions during treatment.