Clinical and immunologic effects of Staphylococcal protein A immunoadsorption therapy for inhibitor to factor VIII

Abstract

A 74-year mild hemophiliac with an inhibitor to factor VIII underwent five 2-L plasma immunoadsorption procedures with a Staphylococcal protein A (Prosorba) column over 7 days. Initially, the inhibitor level increased from 56 to 154 BU/mL. Serum immunoglobulins, immune complexes, C3 and C4 fell progressively with each procedure: C3a was increased. Before therapy, the patient had increased cytotoxic T and activated T cells which decreased to the normal range with treatment. The proportion of T inducer cell and CD4:CD3 ratios increased progressively with each treatment. Natural killer cell activity remained unchanged. Unstimulated patient lymphocytes showed high proliferative activity, but after therapy there was markedly reduced response to mitogens. Both patient and normal lymphocytes showed marked increase in thymidine incorporation when incubated with adsorbed plasma (from column outlet), compared to incubation with unadsorbed plasma (column inlet). The patient's serum showed a progressive rise in this “mitogenicity” effect, maximal after the third procedure, then declining to pre-treatment levels after the fifth procedure. After the third immunoadsorption, inhibitor level was 70 BU/mL and he was given prednisone and cyclophosphamide; after the fifth procedure it was 32 BU/mL and 6 months later was undetectable. Although subsequent decrease in the inhibitor may have been due to the plasma immunoadsorption, it is important to note that this treatment may be paradoxically associated with a rise in antibody levels. In addition to antibody changes, Staph. protein A perfusion affected cellular immunity.