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


CONCLUSIONS
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.
Suzuki
K
K
Department of Allergy and Rheumatology, University of Tokyo School of Medicine, Tokyo, Japan
Sawada
T
T
Murakami
A
A
Matsui
T
T
Tohma
S
S
Nakazono
K
K
Takemura
M
M
Takasaki
Y
Y
Mimori
T
T
Yamamoto
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D002956:Citrulline / Q000276:immunology*; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000276:immunology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D012372:ROC Curve; D011994:Recombinant Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012217:Rheumatoid Factor / Q000097:blood; D012680:Sensitivity and Specificity
D001323:Autoantibodies; D017931:DNA Primers; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; D002956:Citrulline; D012217:Rheumatoid Factor; D019278:Matrix Metalloproteinase 3