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The prevalence of anticitrullinated protein antibodies increases with age in healthy individuals at risk for rheumatoid arthritis

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Abstract

Transition from genetic risk to the development of systemic autoimmunity associated with rheumatoid arthritis (RA) is considered a key step for the development of RA and often referred to as the immune onset of the disease. The aim of this study is to identify predictors for the presence of anticitrullinated protein antibodies (ACPA) as a marker of systemic autoimmunity associated with RA in a high-risk population, an ongoing cohort of first-degree relatives of patients with RA. We assessed the presence of ACPA in individuals without clinical evidence of RA. We examined characteristics associated with ACPA positivity using general estimation equations to account for multiple observations per individual. A total of 1159 serum samples from 1025 subjects were analyzed, 69 samples (6%) were ACPA-positive, and 227 (20%) positive for rheumatoid factor. Participants had a median age of 45 years (interquartile range (IQR): 33–55) at baseline and 76% were women. Overall, ACPA positivity increased with age (p < 0.001). Among women, ACPA positivity was particularly associated with the age group 45 to 55 years (p = 0.003), but not among men (p = 0.7). In multivariable adjusted analyses, age older than 45, female sex and tobacco smoking were independently associated with ACPA positivity. In our cohort, the presence of ACPA was associated with older age and peaked in women around age 45 to 55 years, the perimenopausal period, suggesting that the development of ACPA may be favored by the decline in ovarian function.

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Acknowledgements

This project received financial support from the Fonds National Suisse de la Recherche Scientifique (3200B0_120639/1–AF). Dr. Deshire Alpizar-Rodriguez granted the Swiss Government Excellence Scholarship for PhD studies of The Federal Commission for Scholarships for Foreign Students. Inova Diagnostics, San Diego, CA, United States, performed some of the laboratory tests including anti-CCP 3 (QUANTA Lite® CCP3 IgG) and RF QUANTA Flash® IgM and IgA.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine Specialties, University Hospitals of Geneva, 26, Ave Beau-Sejour, CH 1211, Geneva, Switzerland

    D Alpizar-Rodriguez, Laure Brulhart, Sylvette Bas, Danielle Gascon, Céline Lamacchia, Kim Lauper, Michael J. Nissen, Delphine S. Courvoisier, Cem Gabay & Axel Finckh

  2. Division of Rheumatology, Immunology and Rehabilitation, Kantonsspital St. Gallen, St. Gallen, Switzerland

    Ruediger B. Mueller

  3. Inselspital, Bern, Switzerland

    Burkhard Möller

  4. HFR, Fribourg, Switzerland

    Jean Dudler

  5. USZ, Zurich, Switzerland

    Adrian Ciurea

  6. USB, Basel, Switzerland

    Ulrich A. Walker, Ines Von Mühlenen & Diego Kyburz

  7. CHUV, Lausanne, Switzerland

    Pascal Zufferey

  8. Inova Diagnostics, San Diego, CA, USA

    Michael Mahler

  9. Division of Immunology and Allergy, Department of Internal Medicine Specialties, University Hospitals and Faculty of Medicine of Geneva, Geneva, Switzerland

    Pascale Roux-Lombard

Authors
  1. D Alpizar-Rodriguez
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  2. Laure Brulhart
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  3. Ruediger B. Mueller
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  4. Burkhard Möller
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  5. Jean Dudler
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  6. Adrian Ciurea
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  7. Ulrich A. Walker
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  8. Ines Von Mühlenen
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  9. Diego Kyburz
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  10. Pascal Zufferey
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  11. Michael Mahler
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  12. Sylvette Bas
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  13. Danielle Gascon
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  14. Céline Lamacchia
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  15. Pascale Roux-Lombard
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  16. Kim Lauper
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  17. Michael J. Nissen
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  18. Delphine S. Courvoisier
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  19. Cem Gabay
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  20. Axel Finckh
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Corresponding author

Correspondence to D Alpizar-Rodriguez.

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Alpizar-Rodriguez, D., Brulhart, L., Mueller, R.B. et al. The prevalence of anticitrullinated protein antibodies increases with age in healthy individuals at risk for rheumatoid arthritis. Clin Rheumatol 36, 677–682 (2017). https://doi.org/10.1007/s10067-017-3547-3

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  • DOI: https://doi.org/10.1007/s10067-017-3547-3

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