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

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  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: England NLM ID: 0057202 Publication Model: Print Cited Medium: Print ISSN: 0009-9104 (Print) Linking ISSN: 00099104 NLM ISO Abbreviation: Clin Exp Immunol Subsets: MEDLINE
    • Publication Information:
      Publication: 2022- : Oxford : Oxford University Press
      Original Publication: Oxford : Blackwell Scientific Publications
    • Subject Terms:
      Autoantigens/*immunology ; DNA/*immunology ; Histones/*immunology ; Lupus Erythematosus, Systemic/*immunology ; Ribonucleoproteins/*immunology; Animals ; Antibodies, Antinuclear/immunology ; Crithidia/immunology ; Cross Reactions ; Epitopes, B-Lymphocyte/immunology ; Fluorescent Antibody Technique/methods ; Humans ; Immunoglobulin G/immunology ; Peptide Fragments/immunology ; Recombinant Proteins/immunology ; Sjogren's Syndrome/immunology ; SS-B Antigen
    • Abstract:
      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.
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    • Accession Number:
      0 (Antibodies, Antinuclear)
      0 (Autoantigens)
      0 (Epitopes, B-Lymphocyte)
      0 (Histones)
      0 (Immunoglobulin G)
      0 (LA protein, human (349-364))
      0 (Peptide Fragments)
      0 (Recombinant Proteins)
      0 (Ribonucleoproteins)
      9007-49-2 (DNA)
    • Publication Date:
      Date Created: 20050924 Date Completed: 20051220 Latest Revision: 20231213
    • Publication Date:
      20231215
    • Accession Number:
      PMC1809500
    • Accession Number:
      10.1111/j.1365-2249.2005.02892.x
    • Accession Number:
      16178873