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Hybridoma lupus autoantibodies can bind major cytoskeletal filaments in the absence of DNA-binding activity.

A panel of 65 systemic lupus erythematosus (SLE) and 61 normal-derived human hybridoma auto-antibodies was studied for cytoskeletal reactivity, using an indirect immunofluorescence method. Reactivity with the cytoskeleton was expressed 3 times more frequently in the SLE-derived antibody group and included intermediate filaments, microfilaments, microtubules, and centrioles. By immunoblot analysis, the antigenic specificity of intermediate filament-reactive SLE hybridoma antibodies was not restricted to vimentin, but included cytokeratins and desmin. The antibodies were also studied for their DNA-binding, lupus anticoagulant, and rheumatoid factor activities. These autoantibody activities were expressed 3-5 times more frequently in the SLE-derived group. The ability to bind DNA was not a prerequisite for reactivity with intermediate filament proteins. Our findings suggest that there are at least 2 subsets of cytoskeletal-reactive hybridoma antibodies: those that recognize epitopes found only on cytoskeletal proteins, and those that recognize epitopes common to both DNA and certain cytoskeletal proteins. In addition, we hypothesize that there may be a third subset of antibodies that recognize a phosphate-containing moiety (phospholipid or phosphoprotein) associated with cytoskeletal filaments.