Immunologic monitoring during OKT3 therapy

Abstract

The monoclonal antibody OKT3 is a potent immunosuppressant inducing both T‐cell depletion and antigenic modulation of the CD3/T‐cell receptor complex. CD3+ lymphocytes are cleared from the circulation within I hour of intravenous administration of OKT3. Periodic monitoring of remaining or reappearing CD3+ lymphocytes gauges the adequacy of OKT3 dosing and OKT3 consumption by anti‐OKT3 antibodies. The maximum acceptable concentration of CD3+ lymphocytes for maintaining the effectiveness of OKT3 therapy remains controversial due to variable sensitivity of the methods used. Intravenously administered OKT3 has a half‐life of approximately 18 hours and results in trough serum levels ranging from 500 to 1000 ng/ml in 3 to 4 days. The antibody response to OKT3 is oligoclonal, and both IgM and IgG antibodies to OKT3 may develop, showing restricted specificity; anti‐isotypic and/or anti‐idiotypic antibodies can be detected. The IgG anti‐idiotypic antibodies are the ones that neutralize the therapeutic activity of OKT3, and their specific detection involves the use of an immunofluorescence method that tests their ability to block the binding of OKT3 to normal T cells. The production of OKT3 antibodies has been shown to be affected by concomitantly administered immunosuppressive agents. Studies have demonstrated that OKT3 can be successfully reused in allograft recipients who do not present anti‐idiotypic blocking antibodies. The acute clinical syndrome regularly observed upon the first OKT3 injection is related to massive, although transient, release of several cytokines, which may be easily monitored with currently available radioimmunologic or immunoenzymatic tests.