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The cytotoxicity of DNA-specific autoantibodies from sera of patients with systemic lupus erythematosis (SLE) and with lymphoproliferative diseases, and from blood of healthy donors was examined on tumor-cell lines L929 and HL-60. DNA-binding IgG fractions from SLE and chronic lymphocytic leukemia (CLL) sera were cytotoxic at concentrations of up to 10(-10) M. No detectable changes in cell viability were observed after incubation with antibodies devoid of DNA-binding activity and DNA-specific antibodies isolated from blood of healthy donors and patients with T-cell lymphoma, B-cell lymphosarcoma, and acute B-cell leukemia. There was good correlation between the cytotoxic activity and DNA-hydrolyzing activity of anti-DNA antibodies. The cytotoxic effect of DNA-binding antibodies presumably was complement-independent, because it was attributed only to the Fab fragment. The cytotoxic effect was completely inhibited by preincubation with double-stranded DNA (dsDNA). Both the cytotoxic effect and the DNA-hydrolyzing activity of anti-DNA antibodies were significantly increased in the antibody fraction that displayed cross-reactivity with nuclear matrix proteins. Possible mechanisms for the formation and pathogenicity of cytotoxic anti-DNA antibodies are discussed in this article.

The anti-desmin monoclonal antibodies (MAbs) DSB389, AC54, and DSB860 recognize intermediate filaments (IFs) and nuclear antigens that appear granular, locate around chromosomes, and are insoluble following 0.5% Triton X-100 and cetyltrimethylammonium bromide (CTAB) extraction. Nuclear antigens of the MAbs were searched for in an IFs-deficient clone of SW13 cells. Reactive materials specific to DSB389, AC54, and DSB860 MAbs were trapped at the top of the gel of SDS-agarose-PAGE. The reactivity of the materials disappeared after treatment with DNase I. The reactivity, or trapping of this material at the top of the gel, required previous heat treatment of the sample before application to the gel. The MAbs recognized both single-stranded and double-stranded DNA in ELISA. These results indicate that at least the main nuclear antigens of DSB389, DSB860 and AC54 MAbs are DNA.