Technical and diagnostic performance of 6 assays for the measurement of citrullinated protein/peptide antibodies in the diagnosis of rheumatoid arthritis.
BACKGROUND
Several anticitrullinated protein/peptide antibodies (ACPA) assays have been reported to be of diagnostic value for rheumatoid arthritis (RA). We evaluated the technical performance and diagnostic accuracy of 6 ELISAs for the detection of antibodies to citrullinated protein/peptide antigens.


METHODS
ACPA were determined in 298 serum samples using 6 commercially available ACPA assays. One hundred two samples were from RA patients, including patients with early and established RA, and 196 were from controls, including patients with psoriatic arthritis, connective tissue diseases, organ-specific autoimmune diseases, and a group of consecutive patients for whom a rheumatologist ordered anticyclic citrullinated peptide (CCP) antibodies. The ELISA reagent sets under study were Citrullinated Protein Antibodies (Genesis), Anti-MCV (Orgentec), Immunoscan RA (Euro-Diagnostica), Anti-CCP IgG ELISA (Euroimmun), EliA CCP (Phadia), and Quanta Lite CCP3 IgG ELISA (Inova). Technical performance (imprecision, linearity, correlation, and agreement) and diagnostic accuracy (sensitivity and specificity) were compared.


RESULTS
Variable technical performance was noted among the different ACPA assays, with some assays displaying poor reproducibility and bad linearity. ACPA results were well correlated among assays with the same antigen specificity, but the numerical values reported for each assay differed widely. Using cutoff values proposed by the manufacturer, diagnostic sensitivities ranged between 69.6% and 77.5% and specificities between 87.8% and 96.4%. The areas under the ROC curves were comparable among the different assays.


CONCLUSIONS
Overall diagnostic performance of ACPA assays is comparable among the different assays, but standardization is needed. For some assays, analytical characteristics could be improved.
Coenen
Dries
D
Departments of Laboratory Medicine & Immunology, University Hospital Leuven, Belgium.
Verschueren
Patrick
P
Westhovens
René
R
Bossuyt
Xavier
X
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D002956:Citrulline / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology; D015203:Reproducibility of Results; D014746:Vimentin / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; D014746:Vimentin; C487763:cyclic citrullinated peptide; D002956:Citrulline