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Specific autoantibodies precede the symptoms of rheumatoid arthritis: A study of serial measurements in blood donors

  1. Markus M. J. Nielen1,
  2. Dirkjan van Schaardenburg2,
  3. Henk W. Reesink3,
  4. Rob J. van de Stadt1,
  5. Irene E. van der Horst-Bruinsma4,
  6. Margret H. M. T. de Koning1,
  7. Moud R. Habibuw3,
  8. Jan P. Vandenbroucke5,
  9. Ben A. C. Dijkmans2,*

Article first published online: 5 FEB 2004

DOI: 10.1002/art.20018

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 50, Issue 2, pages 380–386, February 2004

Additional Information

How to Cite

Nielen, M. M. J., van Schaardenburg, D., Reesink, H. W., van de Stadt, R. J., van der Horst-Bruinsma, I. E., de Koning, M. H. M. T., Habibuw, M. R., Vandenbroucke, J. P. and Dijkmans, B. A. C. (2004), Specific autoantibodies precede the symptoms of rheumatoid arthritis: A study of serial measurements in blood donors. Arthritis & Rheumatism, 50: 380–386. doi: 10.1002/art.20018

Author Information

  1. 1

    Jan van Breemen Institute, Amsterdam, The Netherlands

  2. 2

    Jan van Breemen Institute and Vrije Universiteit Medical Centre, Amsterdam, The Netherlands

  3. 3

    Sanquin Blood Bank Northwest Region, Amsterdam, The Netherlands

  4. 4

    Vrije Universiteit Medical Centre, Amsterdam, The Netherlands

  5. 5

    Leiden University Medical Center, Leiden, The Netherlands

*Department of Rheumatology, Vrije Universiteit Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands

Publication History

  1. Issue published online: 5 FEB 2004
  2. Article first published online: 5 FEB 2004
  3. Manuscript Accepted: 1 OCT 2003
  4. Manuscript Received: 15 MAY 2003

Funded by

  • Dutch Arthritis Association

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Abstract

Objective

Autoantibodies have been demonstrated in single serum samples from healthy subjects up to 10 years before they developed rheumatoid arthritis (RA). However, the time course for the development of antibodies before onset of clinical RA is unknown, nor is it known which antibody, or combinations of antibodies, might be most sensitive or specific for predicting future development of the disease. The present study was undertaken to investigate this.

Methods

Patients with RA who had been blood donors before the onset of disease symptoms were enrolled. Frozen serum samples from each donor were retrieved, together with 2 serum samples from controls matched for age, sex, and date of donation. All samples were tested for IgM rheumatoid factor (IgM-RF) and anti–cyclic citrullinated peptide (anti-CCP) antibodies.

Results

Seventy-nine patients with RA (62% female; mean age at onset of symptoms 51 years) were included. A median of 13 samples (range 1–51) per patient were available; the earliest samples had been collected a median of 7.5 years (range 0.1–14.5) before the onset of symptoms. Thirty-nine patients (49%) were positive for IgM-RF and/or anti-CCP on at least one occasion before the development of RA symptoms, a median of 4.5 years (range 0.1–13.8) before symptom onset. Of the 2,138 control samples, 1.1% were positive for IgM-RF, and 0.6% were positive for anti-CCP.

Conclusion

Approximately half of patients with RA have specific serologic abnormalities several years before the onset of symptoms. A finding of an elevated serum level of IgM-RF or anti-CCP in a healthy individual implies a high risk for the development of RA. We conclude that IgM-RF and anti-CCP testing with appropriately high specificity may assist in the early detection of RA in high-risk populations.

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