Antibodies to a strain-specific citrullinated Epstein-Barr virus peptide diagnoses rheumatoid arthritis

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Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Anti-citrullinated protein antibodies (ACPA) are crucial for the serological diagnosis of RA, where Epstein-Barr virus (EBV) has been suggested to be an environmental agent in triggering the onset of the disease. This study aimed to analyse antibody reactivity to citrullinated EBV nuclear antigen-2 (EBNA-2) peptides from three different EBV strains (B95-8, GD1 and AG876) using streptavidin capture enzyme-linked immunosorbent assay. One peptide, only found in a single strain (AG876), obtained a sensitivity and specificity of 77% and 95%, respectively and showed high sequence similarity to the filaggrin peptide originally used for ACPA detection. Comparison of antibody reactivity to commercial assays found that the citrullinated peptide was as effective in detecting ACPA as highly sensitive and specific commercial assays. The data presented demonstrate that the citrullinated EBNA-2 peptide indeed is recognised specifically by RA sera and that the single peptide is able to compete with assays containing multiple peptides. Furthermore, it could be hypothesized that RA may be caused by (a) specific strain(s) of EBV.


  • Nicole Hartwig Trier
  • Bettina Eide Holm
  • Julie Heiden
  • Ole Slot
  • Henning Locht
  • Hanne Lindegaard
  • Anders Svendsen
  • Christoffer Tandrup Nielsen
  • Søren Jacobsen
  • Elke Theander
  • Gunnar Houen
External organisations
  • Danish Serum Institute, Copenhagen
  • Glostrup Hospital
  • Frederiksberg Hospital
  • Odense University Hospital
  • University of Southern Denmark
  • Copenhagen University Hospital
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity
Original languageEnglish
Article number3684
JournalScientific Reports
Issue number1
Publication statusPublished - 2018 Dec 1
Publication categoryResearch
Externally publishedYes