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.
Senécal
J L
JL
Department of Medicine, University of Montreal School of Medicine, Quebec, Canada.
Rauch
J
J
D000328:Adult; D000906:Antibodies / Q000032:analysis / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D003599:Cytoskeleton / Q000276:immunology* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D006825:Hybridomas / Q000276:immunology*; D007158:Immunologic Techniques; D007382:Intermediate Filaments / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged
D000906:Antibodies; D001323:Autoantibodies; D004247:DNA