Effects of long-term procainamide therapy on immunoglobulin synthesis

Procainamide is a potent inducer of autoantibodies. In order to evaluate the immunologic effects of this drug in vivo, 23 cardiac disease patients who had received procainamide for at least 6 months and an equal number of matched cardiac disease control subjects were studied, and percentage of circulating T cell subsets, concanavalin A-induced suppressor cell activity, and pokeweed mitogen--stimulated generation of immunoglobulin-secreting cells was quantitated. There was no significant difference between patient and control groups in the percentage of T cell subsets defined by OKT4 and OKT8 monoclonal antibodies or in concanavalin A-induced suppressor cell activity. The numbers of pokeweed mitogen--induced immunoglobulin-secreting cells were markedly decreased in the patient group, as measured by the protein A-augmented reverse hemolytic plaque assay (3,000 +/- 644, mean +/- SEM in patients versus 10,826 +/- 1,529, mean +/- SEM in control subjects, P less than 0.005). Removal of the adherent cell fraction did not improve the hyporesponsiveness. When B and T cell fractions of 6 patients were mixed with normal T and B cell fractions, all of the patients demonstrated diminished B cell responses, and one-half also had diminished T cell responses. Addition of patient adherent cells to a co-culture of normal B cells with deficient patient T cells restored plaque formation to normal levels, suggesting that the T cell defect was correctable by a macrophage-derived factor. The data obtained suggest that procainamide exerts an immuno-suppressive action on both B and T cell function in patients receiving this drug.