Untitled

Abstract

Anti-Sm antibodies, identified in 1966 by Tan and Kunkel, are highly specific serological markers for systemic lupus erythrematosus (SLE). Anti-Sm reactivity is found in 5-30% of SLE patients, depending on the autoantibody detection system and the racial background of the SLE population. The Sm autoantigen complex comprises at least nine different polypeptides. All of these core proteins can serve as targets of the anti-Sm B-cell response, but most frequently the B and D polypeptides are involved. Because the BB'Sm proteins share cross-reactive epitopes (PPPGMRPP) with U1 specific ribonucleoproteins, which are more frequently targeted by antibodies that are present in patients with mixed connective tissue disease, the SmD polypeptides are regarded as the Sm autoantigens that are most specific to SLE. It was recently shown that the polypeptides D1, D3 and BB' contain symmetrical dimethylarginine, which is a component of a major autoepitope within the carboxyl-terminus of SmD1. In one of those studies, a synthetic dimethylated peptide of SmD1 (amino acids 95-119) exhibited significantly increased immunoreactivity as compared with unmodified SmD1 peptide. Using immobilized peptides, we confirmed that the dimethylated arginine residues play an essential role in the formation of major SmD1 and SmD3 autoepitopes. Moreover, we demonstrated that one particular peptide of SmD3 represents a more sensitive and more reliable substrate for the detection of a subclass of anti-Sm antibodies. Twenty-eight out of 176 (15.9%) SLE patients but only one out of 449 (0.2%) control individuals tested positive for the anti-SmD3 peptide (SMP) antibodies in a new ELISA system. These data indicate that anti-SMP antibodies are exclusively present in sera from SLE patients. Thus, anti-SMP detection using ELISA represents a new serological marker with which to diagnose and discriminate between systemic autoimmune disorders.

Synthetic Peptides for the Immunodiagnosis of Human Diseases

“…The antigenic analytes employed in these tests included purified native proteins, recombinant polypeptides and synthetic peptides [117]. In a recent study, a highly specific Sm peptide comprising the sequence 108-122 of the SmD3 protein and containing a dimethylarginine residue at position 112 has been identified and used for the development of a reliable ELISA system for the detection of a sub-population of anti-Sm antibodies [118]. Mahler et al [119] have compared the clinical accuracy of anti-Sm autoantibody assays from commercial suppliers including different conventional ELISA systems based on purified Sm antigens, an addressable laser bead assay and the newly developed anti-Sm peptide assay.…”

“…The results showed that acute hepatitis A patient sera preferentially recognized homogeneous two branched MAPs and palmitic acid conjugated peptides. The palmitoylderived VP3 (110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121) peptide and the corresponding dimeric MAP were the most sensitive and appropriate for serological studies of HAV-infected patients by ELISA, sensitivity and specificity being higher than 90% and 95%, respectively.…”

Evaluating Anti-SmD1-amino-acid 83-119 Peptide Reactivity in Children with Systemic Lupus Erythematosus and Other Immunological Diseases

“…The IMTEC SmD1 83-119 peptide contains the symmetrical dimethylarginine modification described by Mahler et al . [14] The EUROIMMUN native Sm antigen was purified from bovine thymus and spleen extracts using affinity chromatography. In brief, after preincubating with blocking buffer, the strip coated with the SmD1 83-119 peptide and additional 11 auto-antigens was incubated with sera diluted at 1:100 in blocking buffer.…”

Interpretation of ANA Indirect Immunofluorescence Test Outside the Darkroom Using NOVA View Compared to Manual Microscopy

“…Diagnoses were established as previously described or according to the respective disease classification criteria [26]. In addition, 99 healthy adult donor sera which consisted of 70% female and 30% male between the ages of 19 to 59 years of age were tested.…”