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Antibodies to citrullinated α-enolase peptide 1 and clinical and radiological outcomes in rheumatoid arthritis
  1. Benjamin A Fisher1,
  2. Darren Plant2,
  3. Monica Brode3,
  4. Ronald F van Vollenhoven4,
  5. Linda Mathsson3,
  6. Deborah Symmons2,
  7. Karin Lundberg4,
  8. Johan Rönnelid3,
  9. Patrick J Venables1
  1. 1Kennedy Institute of Rheumatology, Imperial College London, UK
  2. 2Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, UK
  3. 3Unit of Clinical Immunology, Uppsala University and Uppsala University Hospital Uppsala, Sweden
  4. 4 Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to Dr Benjamin Fisher, Department of Rheumatology, Charing Cross Hospital, Fulham Palace Road, London; benjamin.fisher{at}


Introduction The anticyclic citrullinated peptide 2 (anti-CCP2) assay is a generic test for antibodies to citrullinated proteins, among which there is a subset of about 50% with antibodies to citrullinated enolase peptide 1 (CEP-1). The anti-CEP-1 positive subset is strongly associated with the HLA-DRB1 shared epitope and its interaction with smoking.

Objective To investigate whether anti-CEP-1 antibodies may be helpful in predicting outcome.

Methods Anti-CEP-1 and anti-CCP2 antibodies were measured in two prospective cohorts of patients (Karolinska n=272, Norfolk Arthritis Register (NOAR) n=408) with early rheumatoid arthritis (RA). Outcomes measured were C-reactive protein, erythrocyte sedimentation rate, visual analogue scales for pain and global assessment of disease activity, Health Assessment Questionnaire, physician's assessment, swollen and tender joint counts and radiological progression.

Results Anti-CCP2 antibodies were present in 57% and 50%, and anti-CEP-1 in 27% and 24% of the Karolinska and NOAR cohorts, respectively. Importantly, no statistically significant differences in clinical outcomes were demonstrated between the anti-CEP-1−/CCP2+ and the anti-CEP-1+/CCP2+ subsets in either cohort, or in radiological outcomes in the Karolinska cohort.

Conclusion Although antibodies to specific citrullinated proteins may have distinct genetic and environmental risk factors, the similarity in clinical phenotype suggests that they share common pathways in the pathogenesis of joint disease in RA.

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  • JR and PJV contributed equally to this work and are joint senior authors.

  • Funding Arthritis Research UK, the Swedish Rheumatism Association and the Swedish Research Council. This study is part of the EU funded research project Autocure, within the 6th Framework Programme.

  • Competing interests A patent for the diagnostic use of the CEP-1 peptide (patent application number: WO0890360, published on 31 July 2008) is jointly held by two of the authors (PJV and KL) and funded by Imperial Innovations, Imperial College London.

  • Ethics approval This study was conducted with the approval of the Norwich research ethics committee and Northern Stockholm ethical committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.