title: How well do ACPA discriminate and predict RA in the general population: a study based on 12 590 population-representative Swedish twins.
abstract: 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.
  
  
  CONCLUSIONS
  Presence of ACPA and especially high titres of anti-CCP2 have a high diagnostic accuracy for an RA diagnosis in a population setting.
authors.affiliation: Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.|Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Aase Haj
authors.initials: AH
authors.lastname: Hensvold
authors.affiliation: Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0002-5735-9626
authors.initials: T
authors.lastname: Frisell
authors.affiliation: Swedish Twin Registry, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Patrik K E
authors.initials: PK
authors.lastname: Magnusson
authors.affiliation: Department of Medical Biochemistry and Biophysics, Section for Medical Inflammation Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.affiliation: Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.|Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
authors.affiliation: Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.|Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anca Irinel
authors.initials: AI
authors.lastname: Catrina
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011237:Predictive Value of Tests; D013548:Sweden
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002097:C-Reactive Protein
keywords: Ant-CCP; Autoantibodies; Rheumatoid Arthritis