Characterization and antigenic specificity of chlorpromazine-induced antinuclear antibodies

Prolonged treatment with chlorpromazine is often associated with the development of antinuclear antibodies, an immunoglobulin M lupus anticoagulant, and polyclonal serum IgM elevation, but not with clinical features of systemic lupus erythematosus (SLE). Sera from 62 long-term psychiatric patients given treatment daily with 100 mg or more of chlorpromazine for at least 1 year were screened for antinuclear antibodies by indirect immunoperoxidase assay using HEp-2 cells. In 26 samples, antinuclear antibody titers greater than or equal to 1:40 with a homogeneous pattern were seen when anti-human IgM was used as the second antibody, three sera samples reacted with IgG, and four samples reacted with both IgG and IgM antisera. The antinuclear antibody antigenic reactivity was investigated by using histone and nonhistone nuclear antigens by enzyme-linked immunosorbent assay and passive hemagglutination techniques. Forty serum samples reacted with histone. Twenty-five samples reacted with deoxyribonucleoprotein (DNP), 28 with single-stranded DNA, and two with double-stranded DNA. No reaction was obtained with the extractable nuclear antigens RNP or Sm. These results indicate that chlorpromazine-induced antinuclear antibodies, like the antinuclear antibodies induced by hydralazine and procainamide, react mainly with histone nuclear antigens. Unlike the hydralazine and procainamide response, in which both IgG and IgM antibodies are demonstrated, the chlorpromazine-induced autoantibodies are predominantly of the IgM class.