Human anti-mouse immunoglobulins in sera of patients treated chronically with monoclonal antibody-purified factor VIII.

In the process of isolation of factor VIII from human plasma making use of immunoadsorbents prepared by coupling monoclonal murine antibodies to resins, trace amounts of murine immunoglobulin G (IgG) antibodies are released from the resin into the final Monoclate product. This trace contamination, amounting to not more than 50 ng/100 units of Monoclate, was assumed to be below the threshold amounts necessary for inducing an immune response. Nevertheless, we have developed a series of highly sensitive and specific radioimmunoassays for the determination of human antibodies of the IgG, IgM, and IgE classes against the murine monoclonal IgG used for purification of Monoclate. Screening of sera from adults and children treated with Monoclate showed that in no case were any antibodies produced in response to injection of Monoclate. Surprisingly, sera from several patients had a high activity against murine IgG both before and after treatment with Monoclate.