Cross-recognition between histones and La/SSB may account for anti-DNA reactivity in SLE patients

Clin Exp Immunol. 2005 Oct;142(1):172-9. doi: 10.1111/j.1365-2249.2005.02892.x.


Antibodies to La/SSB are detected in sera of patients with primary Sjogren's syndrome (pSS) and systemic lupus erythematosus (SLE). The vast majority of anti-La/SSB positive sera contain antibodies directed towards a linear B-cell epitope of La/SSB spanning the sequence 349-364aa (pep349-364). The aim of this study was to evaluate the fluctuation of antibody levels to major B-cell epitopes of La/SSB over time and investigate for their possible crossreactions. Sequential sera from 15 SLE and 15 pSS patients, followed from 3 to 10 years were obtained. All patients with SLE were positive for anti-Ro/SSA, anti-La/SSB and anti-dsDNA antibodies and patients with pSS were positive for anti-Ro/SSA and anti-La/SSB antibodies. Sera from 30 patients with SLE without anti-La/SSB antibodies and 30 healthy individuals served as disease and negative control respectivelly. All sera tested for the presence of anti-pep349-364 antibodies, using a specific ELISA. Specific anti-pep349-364 IgG was purified from sera of SLE patients and evaluated for cross reactivity against dsDNA and histones. In all SLE sera the levels of anti-pep349-364 antibodies varied in time and fluctuated in parallel with anti dsDNA antibodies. Anti-pep349-364 IgG purified from 7 SLE patients. Five out of 7 were found to react with calf thymus DNA in ELISA. All purified (7/7) anti-pep349-364 IgG preparations reacted with histone H1 and failed to produce a positive immunofluorescence pattern in Crithidia luciliae anti-dsDNA assay which lacks histones. Competative inhibition experiments demonstrated that histone H1 could inhibit completely the binding of anti-pep349-364 IgG to pep349-364 while pep349-364 inhibited by 70% the binding of anti-pep349-364 IgG to histone H1. These findings indicate that a subgroup of SLE patients possess cross-reacting anti-histone H1 antibodies and anti-pep349-364 antibodies, which can be faulty considered as anti-dsDNA reactivity in regular ELISA techniques.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / immunology
  • Autoantigens / immunology*
  • Crithidia / immunology
  • Cross Reactions
  • DNA / immunology*
  • Epitopes, B-Lymphocyte / immunology
  • Fluorescent Antibody Technique / methods
  • Histones / immunology*
  • Humans
  • Immunoglobulin G / immunology
  • Lupus Erythematosus, Systemic / immunology*
  • Peptide Fragments / immunology
  • Recombinant Proteins / immunology
  • Ribonucleoproteins / immunology*
  • Sjogren's Syndrome / immunology


  • Antibodies, Antinuclear
  • Autoantigens
  • Epitopes, B-Lymphocyte
  • Histones
  • Immunoglobulin G
  • LA protein, human (349-364)
  • Peptide Fragments
  • Recombinant Proteins
  • Ribonucleoproteins
  • SS-B antigen
  • DNA