Lymphocyte alteration by procainamide: relation to drug-induced lupus erythematosus syndrome

Sera from 11 (65%) of 17 patients with newly diagnosed procainamide-induced lupus contained cold-reactive lymphocytotoxic antibodies to normal human lymphocytes in titres of 1/2 to 1/128. In contrast, only 3 of 15 patients on long-term procainamide therapy without lupus and 3 of 65 normal men had serum lymphocytotoxic antibodies, none at a titre higher than 1/2. Antibody levels in the lupus patients declined quickly after procainamide was stopped, in parallel with their clinical improvement. Procainamide (3.75 x 10(-3) mol/l) suppressed by more than 80% in-vitro phytohaemagglutinin-induced 3H-thymidine incorporation by normal human blood lymphocytes. At 3.75 x 10(-4) mol/l, procainamide enhanced the mitogenic response to 160 +/- 20% of normal. Thus procainamide may interact with the lymphocyte membrane, possibly producing a lupus syndrome directly, by altering lymphocyte function, or indirectly, by generating autoantibodies reactive with normal membrane structures.