Reactivity of autoantibodies and DNA/anti-DNA complexes with a novel 110-kilodalton phosphoprotein in systemic lupus erythematosus and other diseases.
Utilizing nonionic detergent lysates of human lymphoid and non-lymphoid cells as substrate, IgM and/or IgG antibodies to a 110-kDa/isoelectric point 5.4 phosphoprotein (110K) was demonstrated in serum from patients with SLE or certain other systemic autoimmune disorders by immunoblotting and immunoprecipitation. Ig of this specificity was not demonstrable in serum from normal individuals, but, in a limited survey, was detected in serum from patients with acute hepatitis A or infectious mononucleosis. 110K shares a number of properties with nucleolin, i.e., identical Mr and isoelectric point, localization in both the nucleus and the cytosol, increased expression in rapidly dividing cells, and shown to be distinct from already defined autoantigens of similar size, i.e., topoisomerase I, PM-Scl, and RNA polymerase I. Because 110K could bind denatured DNA, as demonstrated by its specific absorption by DNA-cellulose and by its reactivity with monoclonal anti-ssDNA antibody in the presence of denatured DNA, special efforts were made to distinguish reactivity of pre-formed DNA/anti-DNA complexes in SLE serum from that due to specific anti-110K autoantibodies. Although binding to 110K could be mediated by DNA and anti-DNA in some SLE sera, the accumulated evidence supports the existence of a major new autoantibody system in SLE, other autoimmune diseases, and certain virus infections.
Division of Rheumatology and Immunology, University of North Carolina, Chapel Hill 27599-7280.
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S
Minota
W N
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Jarjour
R A
RA
Roubey
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T
Mimura
J B
JB
Winfield
D000974:Antibodies, Antinuclear / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015153:Blotting, Western; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D007526:Isoelectric Point; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008970:Molecular Weight; D010750:Phosphoproteins / Q000276:immunology*; D019000:Phosphotyrosine; D011233:Precipitin Tests; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D004268:DNA-Binding Proteins; D007075:Immunoglobulin M; D010750:Phosphoproteins; D019000:Phosphotyrosine; D014443:Tyrosine; D004247:DNA