title: Studies of human polyclonal and monoclonal antibodies binding to lupus autoantigens and cross-reactive antigens.
abstract: BACKGROUND
  Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease serologically characterized by production of a variety of autoantibodies. Antibodies to double-stranded (ds) DNA are considered to be a diagnostic marker in SLE and their presence often correlates with active disease. The murine R4A anti-dsDNA antibody was found to cross-react with a peptide, D/EWD/EYS/G (R4A peptide), identified by analysing decapeptides selected from a peptide library. The R4A peptide inhibited binding of antibody to dsDNA and antibody deposition in kidneys in vivo. In other previous work, mice immunized with the peptide in a decapeptide form bound to a polylysine backbone, multiple antigenic peptide, were found to develop both anti-DNA and anticardiolipin antibodies.
  
  
  METHODS
  To determine if human anti-DNA antibodies bind R4A peptide, we investigated the binding of monoclonal and polyclonal anti-dsDNA and anticardiolipin antibodies to the R4A peptide from patients with SLE.
  
  
  RESULTS
  DNA binding by four immunoglobulin (Ig) G and two IgM human monoclonal anti-DNA antibodies was inhibited by the R4A peptide. While monomeric peptide was unable to inhibit affinity-purified polyclonal anti-DNA antibodies, serum anti-DNA reactivity was inhibited by an octameric form of the peptide in 10 SLE patients.
  
  
  CONCLUSIONS
  Human anti-DNA reactivity includes the same fine specificity as that present in murine anti-DNA reactivity. Peptide binding might be a useful surrogate marker for SLE.
authors.affiliation: Centre for Rheumatology, University College London, London W1T 4NJ, UK.
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.forename: D
authors.initials: D
authors.lastname: Isenberg
authors.forename: B
authors.initials: B
authors.lastname: Diamond
mesh_terms: D000328:Adult; D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000276:immunology; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D001667:Binding, Competitive; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology
chemical_list: D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010446:Peptide Fragments