Identification of an acidic ribosomal protein reactive with anti-Sm autoantibody.
Autoantibody to Sm Ag is a highly specific marker for the diagnosis of SLE. The Sm Ag exists in the cell nucleus as part of a ribonucleoprotein complex containing five small nuclear RNA. The major immunoreactive Sm species have been reported to be three polypeptides of m.w. 28,000/29,000 (B/B') and 16,000 (D). We report here that a m.w. 21,000 peptide is another major target of anti-Sm antibody. This peptide was originally identified by Western blotting as an acidic ribosomal protein (RP21) reactive with IgG from some SLE patients. Anti-RP21 is distinct from anti-ribosomal P protein antibody (anti-P) which has been previously identified as a lupus-specific autoantibody. Cell fractionation experiments showed that RP21 existed only in the ribosomal fraction and was never detected in other cellular compartments including nuclei. However, when nuclear extracts were used as Ag sources in immunoblotting, affinity-purified anti-RP21 was found to react with m.w. 28,000 and 16,000 peptides, suggesting that anti-RP21 reactivity might be due to the cross-reaction of anti-Sm. This was further confirmed by the evidence that two kinds of murine anti-Sm mAb independently derived from MRL/lpr mouse recognized RP21. These results indicate that anti-Sm antibodies in SLE are reactive with both nuclear and ribosomal ribonucleoproteins. Previous reports have described certain similarities, i.e., antibody subclass restriction and incidence, of anti-Sm and anti-P in both humans and autoimmune mice. Our present study demonstrated a close physical association of target molecules reactive with anti-Sm and anti-P, and might, therefore, provide some clue to the origin of these two types of lupus-specific autoantibodies.
Nojima
Y
Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Minota
S
S
Yamada
A
A
Takaku
F
F
D000818:Animals; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology* / Q000302:isolation & purification; D001666:Binding Sites, Antibody; D015153:Blotting, Western; D003429:Cross Reactions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007106:Immune Sera / Q000494:pharmacology; D007526:Isoelectric Point; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051381:Rats; D012261:Ribonucleoproteins / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear; D012269:Ribosomal Proteins / Q000276:immunology* / Q000302:isolation & purification; D055517:snRNP Core Proteins
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D007106:Immune Sera; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D012269:Ribosomal Proteins; D055517:snRNP Core Proteins