High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis

Scand J Rheumatol. 2003;32(4):197-204. doi: 10.1080/03009740310003677.


Objective: We investigated the rheumatoid arthritis (RA) diagnostic performances of anti-cyclic citrullinated peptide antibody (anti-CCP) and antifilaggrin antibody (AFA) in comparison with RF and matrix metalloproteinase-3 (MMP-3).

Methods: We used a second generation enzyme-linked immunosorbent assay (ELISA) kit for the detection of anti-CCP. We constructed recombinant human filaggrin, which was citrullinated in vitro by human peptidylarginine deiminase, and subsequently used it as the coating antigen for AFA-ELISA. A total of 549 RA patients and 208 other rheumatic disease patients were included in the study.

Results: The specificities of anti-CCP (88.9%) and AFA (94.7%) were superior to those of RF (81.7%) and MMP-3 (49.5%). The sensitivity of anti-CCP (87.6%) was superior to all others. However, the sensitivity of AFA (68.7%) was inferior to those of RF (69.8%) and MMP-3 (75.7%). Furthermore, receiver operating characteristic curves of anti-CCP and AFA passed closer to the upper left corner than those of RF and MMP-3, and the areas under the curves (AUC) of AFA and anti-CCP were significantly larger. In addition, the AUC of anti-CCP was significantly larger than that of AFA.

Conclusion: ELISA detection of antibodies to citrullinated antigens, especially a second generation anti-CCP, showed higher discriminative ability than other assays, including RF, and would be useful to aid the diagnosis of RA in clinical practice.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood*
  • Citrulline / immunology*
  • DNA Primers / chemistry
  • Enzyme-Linked Immunosorbent Assay*
  • Female
  • Filaggrin Proteins
  • Humans
  • Intermediate Filament Proteins / immunology
  • Male
  • Matrix Metalloproteinase 3 / blood
  • Middle Aged
  • Peptides, Cyclic / immunology
  • ROC Curve
  • Recombinant Proteins / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rheumatoid Factor / blood
  • Sensitivity and Specificity


  • Autoantibodies
  • DNA Primers
  • FLG protein, human
  • Filaggrin Proteins
  • Intermediate Filament Proteins
  • Peptides, Cyclic
  • Recombinant Proteins
  • Citrulline
  • Rheumatoid Factor
  • Matrix Metalloproteinase 3