title: Lack of immune response to mouse IgG in previously untreated haemophilia A and haemophilia B patients treated with monoclonal antibody purified factor VIII and factor IX preparations.
abstract: Immunoaffinity purification of factor VIII and factor IX results in the inclusion of trace quantities (50 ng 100 IU(-1) ) of mouse protein in the final product. It is possible that infusion of extremely low levels of proteins might induce human antimouse antibody (HAMA) responses. To test this possibility, IgG, IgM and IgE antibodies to mouse IgG were assessed in previously untreated haemophilia A and haemophilia B patients (n = 9 and n = 11, respectively) who received monoclonal antibody (MAb) purified factor VIII (Monoclate-P® Antihaemophilic Factor [Human] Centeon, King of Prussia, PA) or factor IX (Mononine® Coagulation Factor IX [Human] Centeon). HAMA were evaluated prior to and 2-42 months after initial treatment. IgE antibodies to mouse IgG were undetectable (< 19 ng ML(-1) ) at all time points. Antimouse IgG levels for Monoclate-P-treated patients averaged (mean±SD) 0.40±0.18 μg mL(-1) prior to treatment, and 0.64±0.43 μg mL(-1) at the time of last observation (P > 0.05, not significant [n.s.]). Respective values for antimouse IgM in these patients were 2.48±1.20 μg mL(-1) and 2.85±1.63 μg mL(-1) (P > 0.05, n.s.). Antimouse IgG levels for Mononine-treated patients averaged 0.48±0.52 μg mL(-1) prior to treatment, and 0.66±0.59 μg mL(-1) after 3 months of therapy (P > 0.05, n.s.). Respective values for antimouse IgM in these pa-tients were 1.94±1.52 μg mL(-1) and 1.77±0.99 μg 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 developed anaphylactoid reactions during treatment.
authors.affiliation: Rhône-Poulenc Rorer Research and Development, Collegeville, PA, USA, and Centeon, L.L.C., Medical and Scientific Affairs Department, King of Prussia, PA, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Davis
authors.affiliation: Rhône-Poulenc Rorer Research and Development, Collegeville, PA, USA, and Centeon, L.L.C., Medical and Scientific Affairs Department, King of Prussia, PA, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Nash
authors.affiliation: Rhône-Poulenc Rorer Research and Development, Collegeville, PA, USA, and Centeon, L.L.C., Medical and Scientific Affairs Department, King of Prussia, PA, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Clymer
authors.affiliation: Rhône-Poulenc Rorer Research and Development, Collegeville, PA, USA, and Centeon, L.L.C., Medical and Scientific Affairs Department, King of Prussia, PA, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Frigo
authors.affiliation: Rhône-Poulenc Rorer Research and Development, Collegeville, PA, USA, and Centeon, L.L.C., Medical and Scientific Affairs Department, King of Prussia, PA, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Bergman
keywords: IgE; IgG; IgM; immune response; murine monoclonal antibody; replacement factor.