Sm peptides in differentiation of autoimmune diseases

Abstract

Systemic lupus erythematosus (SLE) and related diseases are characterized by circulating autoantibodies to defined intracellular targets. Among the earliest identified autoantibodies were those directed to components of U2-U6 small nuclear ribonucleoproteins (snRNPs) known as Smith (Sm) antigen, which are highly specific for SLE. The Sm-antigen is composed of at least nine different polypeptides with molecular weights ranging from 9 to 29.5 kDa (B (B1, 28 kDa), B' (B2, 29 kDa), N (B3, 29.5 kDa), D1 (16 kDa), D2 (16.5 kDa), D3 (18 kDa), E (12 kDa), F (11 kDa), and G (9 kDa)). All of the nine core proteins, but most frequently the B and D polypeptides, are targets of the anti-Sm autoimmune response. However, since SmBB' and U1 specific RNPs share the cross-reactive epitope motif PPPGMRPP, SmD is regarded as the most SLE specific Sm-antigen. It has been shown that the polypeptides D1, D3, and BB' contain symmetrical dimethylarginine, constituting a major autoepitope within the C-terminus of SmD1 and SmD3. Several synthetic peptides have been used for the detection of anti-Sm antibodies and thus for the diagnosis of SLE. Anti-Sm antibodies have been reported to occur later than other SLE associated autoantibodies and, on average, around 1 year before the clinical onset of SLE. The present review provides a comprehensive summary on the history of anti-Sm antibodies and their use as biochemical tools to study cellular processes and as biomarker in the diagnosis of SLE. Additionally, a meta-analysis focused on recent data analyzes the prevalence of anti-Sm antibodies in SLE.