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Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression
  1. J Rönnelid1,
  2. M C Wick2,
  3. J Lampa2,
  4. S Lindblad2,
  5. B Nordmark2,
  6. L Klareskog2,
  7. R F van Vollenhoven2
  1. 1Unit of Clinical Immunology, Department of Oncology, Radiology and Clinical Immunology, Uppsala University/Akademiska Hospital, Uppsala, Sweden
  2. 2Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden
  1. Correspondence to:
    Dr J Rönnelid
    Unit of Clinical Immunology, Rudbeck Laboratory C5, SE-75185 Uppsala, Sweden;


Objective: To study serum levels of citrullinated protein/peptide antibodies (anti-CP) during up to 5 years’ follow up of patients with early rheumatoid arthritis (RA), and to relate serum levels to disease course and to treatments in clinical practice.

Methods: 279 patients with early RA were followed up with clinical investigations, radiographs, and measurement of anti-CP at baseline and after 3 months, 1, 2, 3, and 5 years.

Results: 160/279 (57.3%) patients were anti-CP positive at the first visit (mean 5 months after first symptoms). During follow up only 11/279 (3.9%) of the patients changed their anti-CP status. Anti-CP levels fell significantly during the first year, and this drop correlated with the extent of sulfasalazine treatment but not with other drugs or clinical indices. Anti-CP positive and negative patients had similar disease activities at baseline, but during follow up the anti-CP positive patients had worse clinical disease and greater radiological progression, despite at least equally intensive antirheumatic treatment.

Conclusions: Anti-CP are stable during the first 5 years of RA, suggesting that events before rather than after onset of clinical manifestations of disease determine this phenotype. The presence of anti-CP at diagnosis predicts a less favourable disease course and greater radiological progression despite antirheumatic treatment, but subsequent changes in antibody levels do not reflect changes in disease activity. Taken together, these observations suggest that anti-CP positive RA is a distinct clinical and pathophysiological entity.

  • anti-CCP, cyclic citrullinated peptide antibodies
  • anti-CP, citrullinated protein/peptide antibodies
  • CRP, C reactive protein
  • DAS28, 28 joint count Disease Activity Score
  • DMARDs, disease modifying antirheumatic drugs
  • ESR, erythrocyte sedimentation rate
  • HAQ, Health Assessment Questionnaire
  • IQR, interquartile range
  • RA, rheumatoid arthritis
  • RF, rheumatoid factor
  • VAS, visual analogue scale
  • anti-citrulline peptide antibodies
  • disease activity
  • longitudinal study
  • radiological progression
  • rheumatoid arthritis

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