Lupus autoantibodies discriminate between the highly homologous Sm polypeptides B/B' and SmN by binding an epitope restricted to B/B'.
The ubiquitous Sm polypeptides B/B' (28 and 29 kD) and the highly homologous tissue-specific Sm N polypeptide (29 kD) share several autoepitopes recognized by systemic lupus erythematosus (SLE) sera. Previous studies on the antigenicity of nuclear antigens recognized by human autoantibodies have not discriminated between ubiquitous and tissue-specific forms. We set out to examine whether a tissue-specific nuclear antigen, Sm N, is autoantigenic in SLE by comparing the immunoreactivity of the most unique sequences in this polypeptide. Synthetic peptides from the two regions of least sequence homology that occur between Sm N and Sm B/B', a dodecamer (amino acid residues 179-190 containing five substitutions) and an undecamer (residues 203-213 containing four substitutions) were coupled to a carrier protein. These conjugates were used to quantify IgG anti-peptide antibodies in sera from patients with SLE. Of 43 sera with anti-Sm specificity, six bound to the B/B' 179-190 peptide but not to the N version. None of 17 anti-Sm-negative SLE sera bound these peptides. The second region of least sequence homology between N and B/B' (203-213) was not antigenic. Our data suggest that a subset of SLE patients with anti-Sm reactivity have IgG autoantibodies capable of discriminating between Sm N and SmB/B' polypeptides by binding a previously unreported SmB/B'-specific autoepitope. The data also indicate that brain and heart-specific anti-Sm antibodies do not exist in SLE sera, suggesting that these tissues do not participate in the induction or maintenance of the autoimmune anti-Sm response.
Huntriss
J D
JD
Clinical Immunology Division, Mathilda and Terence Kennedy Institute of Rheumatology, London, UK.
Latchman
D S
DS
Williams
D G
DG
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology; D013997:Time Factors; D055517:snRNP Core Proteins
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D010455:Peptides; D017411:Ribonucleoproteins, Small Nuclear; C526407:SNRPB protein, human; C526417:SNRPN protein, human; D055517:snRNP Core Proteins