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Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis
  1. C Turesson1,
  2. L T H Jacobsson1,
  3. G Sturfelt2,
  4. E L Matteson3,
  5. L Mathsson4,
  6. J Rönnelid4
  1. 1Department of Rheumatology, Malmö University Hospital, Malmö, Sweden
  2. 2Lund University Hospital, Lund, Sweden
  3. 3Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
  4. 4Department of Clinical Immunology and Transfusion Medicine, Uppsala University Hospital, Uppsala, Sweden
  1. Correspondence to:
    Dr Carl Turesson
    Department of Rheumatology, Malmö University Hospital, Södra Förstadsgatan 101, S-205 02 Malmö, Sweden; turesson.carl{at}


Objective: To study antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor in patients with active, severe extra-articular rheumatoid arthritis (ExRA) compared with controls without ExRA.

Methods: 35 consecutive patients with severe ExRA manifestations according to predefined criteria were studied. 70 patients with rheumatoid arthritis, but no ExRA manifestations, individually matched for age, sex and disease duration, served as controls. Patients were included when ExRA was diagnosed, before any new treatment was started. Anti-CCPs were detected with ELISA, rheumatoid factor was quantified using nephelometry and anti-nuclear antibodies (ANA) were investigated using indirect immune fluorescence.

Results: Anti-CCPs were detected in 77% of patients with ExRA versus 56% of controls without ExRA (p = 0.03). Anti-CCP levels also tended to be higher in patients with ExRA (p = 0.09). Rheumatoid factor was detected in 94% v 71% of patients and controls, respectively (p = 0.006), and rheumatoid factor levels were higher in patients with ExRA (median interquartile range (IQR) 245 IU/ml (94–604) v 73 IU/ml (not detected–165); p = 0.001). Levels and occurrence of ANA did not differ between patients with ExRA and controls. Patients with ExRA had higher swollen joint counts and C reactive protein levels, but no correlations were found between anti-CCP or rheumatoid factor levels and these measures within the ExRA group.

Conclusion: Rheumatoid factor is strongly associated with severe ExRA manifestations in patients with rheumatoid arthritis, and a similar but weaker association exists for anti-CCPs. This suggests a role for rheumatoid factor and anti-CCP in the pathogenesis of ExRA.

  • ANA, anti-nuclear antibodies
  • anti-CCP, antibodies to cyclic citrullinated peptides
  • CCP, cyclic citrullinated peptides
  • CRP, C reactive protein
  • ExRA, extra-articular rheumatoid arthritis
  • HAQ, Health Assessment Questionnaire
  • IQR, interquartile range

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  • Published Online First 10 August 2006

  • Funding: This study was supported by Lund University, the Åke Viberg Foundation and the Swedish Rheumatism Association. JR was supported by the Swedish Research Council during the study.

  • Competing interests: None.