Autoantibodies to double-stranded (ds)DNA immunoprecipitate 18S ribosomal RNA by virtue of their interaction with ribosomal protein S1 and suppress in vitro protein synthesis.
We report that four systemic lupus erythematosus (SLE) patient sera containing anti-dsDNA antibodies, three affinity-purified anti-dsDNA IgG, and a human anti-dsDNA MoAb (33.H11) immunoprecipitate 18S ribosomal RNA from DNase-treated 32P-labelled MOLT4 cell extract. This 18S RNA precipitation was inhibited completely by preincubating 33.H11 with calf thymus dsDNA or the recombinant human ribosomal protein S1, which was reported to cross-react with anti-dsDNA antibodies (J Immunol 1996; 156:1668-75). Whole IgG from three SLE sera with anti-dsDNA antibodies, 33.H11, and three affinity-purified anti-dsDNA IgG inhibited in vitro translation of globin mRNA (percent inhibition was 36-50%). This translation inhibition by anti-dsDNA antibodies was enhanced (67-79%) when the reticulocyte lysate was treated with DNase. Suppression of protein synthesis could be a pathogenic mechanism of anti-dsDNA antibodies, since it has also been shown that anti-dsDNA penetrates living cells (J Immunol 1995; 154:4857-64) in culture.
Tsuzaka
K
K
Oklahoma Medical Research Foundation, Oklahoma University Health Sciences Centre, Oklahoma City 73104, USA.
Winkler
T H
TH
Kalden
J R
JR
Reichlin
M
M
D000974:Antibodies, Antinuclear / Q000276:immunology* / Q000494:pharmacology*; D002460:Cell Line; D003429:Cross Reactions / Q000276:immunology; D004247:DNA / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors / Q000276:immunology* / Q000378:metabolism*; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects*; D012337:RNA, Ribosomal, 18S / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000276:immunology / Q000378:metabolism; D013491:Suppressor Factors, Immunologic / Q000276:immunology*
D000974:Antibodies, Antinuclear; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors; D011506:Proteins; D012337:RNA, Ribosomal, 18S; D012261:Ribonucleoproteins; D013491:Suppressor Factors, Immunologic; D004247:DNA