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Simultaneous development of acute phase response and autoantibodies in preclinical rheumatoid arthritis
  1. M M J Nielen1,
  2. D van Schaardenburg1,2,
  3. H W Reesink3,
  4. J W R Twisk4,
  5. R J van de Stadt1,
  6. I E van der Horst-Bruinsma2,
  7. M H M T de Koning1,
  8. M R Habibuw2,
  9. B A C Dijkmans2
  1. 1Jan van Breemen Institute, Amsterdam, The Netherlands
  2. 2Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands
  3. 3Sanquin Bloodbank North West Region, Amsterdam, The Netherlands
  4. 4Department of Clinical Epidemiology and Biostatistics, VU University Medical Centre, Amsterdam, The Netherlands
  1. Correspondence to:
    Professor B A C Dijkmans
    Vrije Universiteit Medical Centre, Department of Rheumatology, PO Box 7057, 1007 MB, Amsterdam; Secr.reumatologie{at}


Objective: To investigate the temporal relationship between onset of inflammation (as measured by secretory phospholipase A2 (sPLA2) and C reactive protein (CRP)) and the presence of autoantibodies (IgM rheumatoid factor (IgM RF) and antibodies against citrullinated peptides (anti-CCP)) in the preclinical phase of rheumatoid arthritis (RA).

Methods: For 79 patients with RA who had been blood donors before the onset of disease, a median of 13 serum samples per patient was available. sPLA2 was measured in patient and matched control samples and related to previous CRP, IgM RF, and anti-CCP measurements. The temporal relationship between the increased markers of inflammation and autoantibodies was analysed with time lag analysis.

Results: IgM RF and anti-CCP concentrations were significantly associated (p<0.001) with concentrations of sPLA2, CRP, and the combination of sPLA2 and CRP at the same time point. However, we found no stronger association between the two autoantibody tests and the three inflammation measures 1, 2, and 3 years before or after a time point than for measurements at the same time, in the whole group or in subgroups of IgM RF and anti-CCP positive patients.

Conclusion: Both the acute phase response and autoantibody formation often develop years before the first symptoms of RA occur, and these phenomena are probably closely connected in time.

  • anti-CCP, antibodies against citrullinated peptides
  • CRP, C reactive protein
  • RA, rheumatoid arthritis
  • RF, rheumatoid factor, sPLA2, secretory phospholipase A2
  • rheumatoid arthritis
  • secretory phospholipase A2
  • inflammation
  • autoantibodies

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  • Published Online First 3 August 2005

  • Competing interest: None.