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How well do ACPA discriminate and predict RA in the general population: a study based on 12 590 population-representative Swedish twins
  1. Aase Haj Hensvold1,2,
  2. Thomas Frisell3,
  3. Patrik K E Magnusson4,
  4. Rikard Holmdahl5,
  5. Johan Askling2,3,
  6. Anca Irinel Catrina1,2
  1. 1Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  2. 2Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  3. 3Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  4. 4Swedish Twin Registry, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
  5. 5Department of Medical Biochemistry and Biophysics, Section for Medical Inflammation Research, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to Dr Aase Haj Hensvold, Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm SE-171 76, Sweden; aase.hensvold{at}


Objective Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA), but the diagnostic accuracy of ACPA in the general population has not been thoroughly assessed. We aimed to assess the diagnostic accuracy of ACPA for RA in the general population and to further characterise the citrullinated peptide recognition pattern.

Methods Serum samples from a large population-representative twin cohort consisting of 12 590 individuals were analysed for the presence of ACPA using anti-CCP2 ELISA. All ACPA-positive samples were further tested on ELISAs for four peptide-specific ACPA. RA cases were identified by linkage to the Swedish National Patient Register at inclusion and after a median follow-up of 37 months (IQR 31–49).

Results 350 out of 12 590 individuals had a positive anti-CCP2 test, measuring ACPA. Of these, 103 had an RA diagnosis at the time of blood donation and inclusion. During a median follow-up of 3 years, an additional 21 of the remaining 247 ACPA-positive individuals developed RA. Overall, a positive anti-CCP2 test had a positive predictive value of 29% for prevalent RA at inclusion (negative predictive value of 99.6%). High titres (>3× cut-off) of anti-CCP2 increased the positive predictive value to 48% (negative predictive value of 99.5%). ACPA-positive individuals without RA had lower anti-CCP2 titres and fewer peptide-specific ACPA than ACPA-positive patients with RA and higher C reactive protein levels than ACPA-negative individuals without RA.

Conclusion Presence of ACPA and especially high titres of anti-CCP2 have a high diagnostic accuracy for an RA diagnosis in a population setting.

  • Rheumatoid Arthritis
  • Autoantibodies
  • Ant-CCP

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  • Handling editor Tore K Kvien

  • Contributors All authors made substantial contributions to (1) conception and design, or analysis and interpretation of data (2) drafting the article or revising it critically for important intellectual content and (3) gave final approval of the version to be published.

  • Funding This work was supported by research funding from Innovative Medicine Initiative BTCure (115142-2), FP7-HEALTH-2012-INNOVATION-1 Euro-TEAM (305549-2), the Initial Training Networks seventh framework programme Osteoimmune (289150), the Swedish Research Council and the Swedish Foundation for Strategic Research.

  • Competing interests RH is a holder of a patent (US Patent 7 148 020) protecting the use of the CitC1 peptide.

  • Ethics approval The Regional Ethical Review Board, Stockholm.

  • Provenance and peer review Not commissioned; externally peer reviewed.