Third generation anti-citrullinated peptide antibody assay is a sensitive marker in rheumatoid factor negative rheumatoid arthritis

Clin Chim Acta. 2012 Dec 24;414:266-72. doi: 10.1016/j.cca.2012.09.015. Epub 2012 Sep 25.


Introduction: We compared 2 anti-citrullinated protein antibody (ACPA) assays using a routine patient cohort.

Methods: Two-hundred ninety-five sera were collected from patients for whom ACPA was ordered and tested for ACPA by QUANTA Lite® CCP 3 (INOVA Diagnostics, Inc., San Diego) and EliA® CCP (CCP, Phadia, Germany). Rheumatoid factor (RF) was determined using Quantex RF(II) (Biokit, Spain).

Results: Acceptable qualitative (96.6%, kappa=0.93) and quantitative agreements (Spearman rho=0.77; p<0.0001) were observed between the two ACPA assays. Nine samples were CCP3+/CCP2- and one sample was CCP2+/CCP3-. Of the 9 CCP3+/CCP2- patients, 6 (66.7%) had RA, one patient had ankylosing spondylitis, one osteoarthritis and one psoriatic arthritis. The CCP3-/CCP2+ patient had juvenile RA. At the manufacturer's cut-offs, the sensitivities and specificities were 77.3%/98.1% (CCP2), 81.6%/96.8% (CCP3) and 65.2%/89.6% (RF), respectively. At 98.7% specificity level, the sensitivities in the total cohort were 59.6% (CCP2) and 69.5% (CCP3) while the sensitivities in the RF-negative group were 49.0% (CCP2) and 57.1% (CCP3). In the RF-negative group, sensitivities for patients with a disease duration of ≤ 5years were 38.7% (CCP2) and 51.6% (CCP3).

Conclusion: Discrimination between RA and non-RA patients was better using CCP3, most pronounced in RF-negative RA.

MeSH terms

  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers / blood
  • Female
  • Humans
  • Immunoassay
  • Male
  • Middle Aged
  • Peptides, Cyclic / blood*
  • Peptides, Cyclic / immunology
  • Sensitivity and Specificity


  • Autoantibodies
  • Biomarkers
  • Peptides, Cyclic
  • cyclic citrullinated peptide