DIAGNOSTIC PERFORMANCE OF ANTI-CYCLIC CITRULLINATED PEPTIDE (CCP) 2 AND CCP3.1 ASSAYS IN EARLY RHEUMATOID ARTHRITIS

Background: Anti-cyclic citrullinated peptide (CCP) antibodies are the most specific markers for rheumatoid arthritis (RA). Different generations of assays have been developed among which the anti-CCP2 and anti-CCP3 assays are most widely used. Objectives: Since some differences between these assays have been reported it was our aim to compare their diagnostic performance and evaluate their usefulness for diagnostics of early RA. Methods: The anti-CCP3.1 assay (Quanta Lite ® CCP3.1 IgG/IgA, Inova Diagnostics) was compared to anti-CCP2 IgG and IgA assays (EliATM CCP, Thermo Fisher Scientific) employing sera of 184 early RA patients, 360 disease controls and 98 healthy subjects. Results: Anti-CCP2 IgG and IgA assays showed high specificity versus healthy subjects (98.9%; 98%) and disease controls (98.8%; 99.4%). Sensitivity was 52.2% for the IgG and 30.4% for the IgA assay, respectively, resulting in high positive likelihood ratios (LR+) of 47.5 (IgG) and 50.7 (IgA). However, IgA antibodies did not show an added diagnostic value since all positive patients were also IgG positive. The anti-CCP3.1 assay was slightly more sensitive than the anti-CCP2 IgG assay (55.4%) but specificity was markedly lower and amounted to 95.9% versus healthy subjects 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 (and 2 of these also for anti-CCP2 IgA). The most common diagnosis of CCP3.1 positive control patients was osteoarthritis (12 patients); six patients suffered from spondyloarthropathies, two patients had reactive arthritis, 10 patients were diagnosed with an autoimmune rheumatic disease (AI RMD) and two patients had osteoporosis. However, at a cut-off of 60 AU/ml only nine disease controls remained positive (3 OA, 1 SpA, 4 AI RMD, 1 ReA) and 3 of them were also positive in the anti-CCP2 assay (ReA, SpA, SLE). When applying 60 AU/ml (high positive) as cut-off value at the early RA cohort, sensitivity (52.7%) became comparable to the anti-CCP2 assay and both specificity (97.5%) and LR+ (21.08) increased substantially. Conclusion: When interpreting the results of anti-CCP assays disease specificity should be taken into account in order to reduce the risk of misclassification and a false positive diagnosis. Disclosure of Interests: Daniela Sieghart Grant/research support from: Thermo Fisher Scientific, Speakers bureau: Thermo Fisher Scientific, Christian Konrad Employee of: Thermo Fisher Scientific, Sascha Swiniarski Employee of: Thermo Fisher Scientific, Helmuth Haslacher: None declared, Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Gunter Steiner Grant/research support from: Thermo Fisher Scientific, Speakers bureau: Thermo Fisher Scientific