DIAGNOSTIC PERFORMANCE OF ANTI-CYCLIC CITRULLINATED PEPTIDE (CCP) 2 AND CCP3.1 ASSAYS IN EARLY RHEUMATOID ARTHRITIS
- Daniela Sieghart, Austria
Abstract
Background and Aims
Anti-cyclic citrullinated peptide (CCP) antibodies are the most specific markers for rheumatoid arthritis (RA). Different generations of assays (CCP1-CCP3) have been developed showing variability regarding their performance. The comparability of different assays is an important issue to address especially in the early stages of disease.
Methods
This study aimed to investigate the diagnostic performance of IgG and IgA anti-CCP2 detected by EliATM (Thermo Fisher Scientific) compared to the combined IgG/IgA Quanta LiteR anti-CCP3.1 assay (Inova Diagnostics) in sera of 184 early RA patients, 98 healthy subjects and 360 disease controls.
Results
Anti-CCP2 IgG and IgA assays showed high specificity versus healthy (98.9%; 98%) and disease controls (98.8%; 99.4%). Sensitivity was 52.2% (IgG) and 30.4% (IgA), respectively, resulting in high positive likelihood ratios of 47.5 (IgG) and 50.7 (IgA). IgA antibodies had no added diagnostic value since all patients were also IgG positive. Anti-CCP3.1 was slightly more sensitive than the anti-CCP2 IgG (55.4%) but specificity was markedly lower and amounted to 95.9% versus healthy and 90.8% versus disease controls resulting in a LR+ of only 6.0. Out of 360 disease controls 33 (9.2%) were found to be positive for CCP3.1 but among these only four (1.1%) were positive for anti-CCP2 IgG. When applying 60 AU/ml (high positive) as cut-off value for CCP3.1, sensitivity (52.7%) became comparable to the anti-CCP2 assay and both specificity (97.5%) and LR+ (21.08) increased substantially.
Conclusions
Thus, specificity of anti-CCP assays should be taken into account when interpreting results in order to reduce the risk of a false positive diagnosis.