Superior performance of the CCP3.1 test compared to CCP2 and MCV in the rheumatoid factor-negative RA population.

Anti-citrullinated protein/peptide antibodies (ACPAs) have recently been identified as sensitive and specific diagnostic and prognostic markers in rheumatoid arthritis (RA). In this study, we wished to assess the diagnostic performance of the third-generation anti-CCP3.1 assay, but with special focus on the rheumatoid factor (RF)-negative RA population. Anti-CCP as well as anti-MCV was tested in 119 RA patients and 118 control patients using second and third-generation assays. Using these optimal cut-off levels, the diagnostic sensitivity of anti-CCP2, CCP3, and CCP3.1 was 74.8, 78.8, and 83.0%, respectively, while the specificity was 95.7, 96.6, and 98.3%, respectively. The diagnostic performance of the CCP3.1 test was significantly better than that of CCP2 (p = 0.041). In addition, the CCP3.1 test performed significantly better than the MCV test as well (p = 0.0003). When the diagnostic performance of the CCP3.1, CCP2, and MCV tests was compared in the 35 RF-negative patients, the CCP3.1 test exerted significantly better performance than the MCV test (p = 0.006), and it also showed a tendency of better performance in comparison with the CCP2 test (p = 0.131). In conclusion, the CCP3.1 assay can significantly increase the sensitivity of ACPA testing in RF-negative RA, as well as in the total RA population.