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Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset
  1. E Berglin1,
  2. T Johansson2,
  3. U Sundin6,
  4. E Jidell3,
  5. G Wadell4,
  6. G Hallmans5,
  7. S Rantapää-Dahlqvist1
  1. 1Department of Rheumatology, University Hospital, Umeå, Sweden
  2. 2Department of Medical Biochemistry and Biophysics/Omnio, University Hospital, Umeå
  3. 3Department of Transfusion Medicine, University Hospital, Umeå
  4. 4Department of Virology, University Hospital, Umeå
  5. 5Department of Nutritional Research, University Hospital, Umeå
  6. 6Clinical Immunology, Karolinska University Hospital, Stockholm, Sweden
  1. Correspondence to:
    Dr Solbritt Rantapää-Dahlqvist
    Department of Public Health and Clinical Medicine, Rheumatology, University Hospital, 901 85 Umeå, Sweden; solbritt.rantapaa.dahlqvist{at}


Objective: To evaluate the significance of antibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RFs), before the onset of rheumatoid arthritis and when presenting as early disease (baseline), for disease activity and progression.

Methods: 93 of a cohort of 138 patients with early rheumatoid arthritis (<12 months of symptoms) had donated blood before symptoms of rheumatoid arthritis (defined as pre-patients) and were identified from among blood donors within the Medical Biobank of northern Sweden. Disease activity (erythrocyte sedimentation rate (ESR), C reactive protein, joint score, global visual analogue scale) and radiological destruction in hands and feet (Larsen score) were assessed at baseline and after two years. Anti-CCP antibodies and RFs were analysed using enzyme immunoassays. HLA shared epitope (SE) alleles (DRB1*0401/0404) were identified.

Results: Patients with anti-CCP antibodies before disease onset had significantly higher Larsen score at baseline and after two years. In multiple regression analyses baseline values of anti-CCP/IgA-RF/IgG-RF/IgM-RF, swollen joint count, and Larsen score significantly predicted radiological outcome at two years. In logistic regression analyses, baseline values of anti-CCP antibodies/IgA-RF, therapeutic response at six months, and swollen joint count/ESR significantly predicted radiological progression after two years. The baseline titre of anti-CCP antibodies was higher in patients with radiological progression and decreased significantly in those with response to therapy. SE allele carriage was associated with a positive test for anti-CCP antibodies in pre-patients and in early rheumatoid arthritis.

Conclusions: Presence of anti-CCP antibodies before disease onset is associated with more severe radiological damage. The titre of anti-CCP antibodies is related to disease severity.

  • ACR, American College of Rheumatology
  • anti-CCP, antibodies against cyclic citrullinated peptide
  • DAS28, 28 joint disease activity score
  • DMARD, disease modifying antirheumatic drug
  • EULAR, European League Against Rheumatism
  • NSHDS, Northern Sweden Health and Disease Study
  • RF, rheumatoid factor
  • SE, shared epitope
  • anti-CCP antibody
  • rheumatoid factors
  • early rheumatoid arthritis
  • radiological outcome
  • titre of anti-CCP antibodies

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  • Published Online First 21 September 2005

  • We gratefully acknowledge Arvi Larsen MD, PhD for teaching us how to estimate the Larsen score. We thank Mrs Marie Eriksson for helpful discussion regarding statistical analysis. The staff of both the Medical Biobank, and the Early Arthritis Clinic, University Hospital of Umeå are gratefully acknowledged. Supported by grants from Swedish Research Council (K2003-74XD-14705-01), King Gustaf V’s 80-Year Fund, the Swedish Rheumatism Association, and the Medical Faculty of Umeå University, Umeå, Sweden.