Background/Purpose:

Anti-CCP testing is a part of the clinical routine investigations for rheumatoid arthritis (RA). Previous studies have relative few included controls per patients. We therefor aimed to screen a large population-based cohort and investigate the diagnostic accuracy of testing anti-CCP, in high concentration, and testing of other ACPAs, for detecting RA.

Methods:

We used a subset of the Swedish twin registry, which includes 12 590 monozygotic and dizygotic twins born 1958 or earlier (median age 65, range 48-93). Cases of RA were identified by linkage to the Swedish National Patient Register and by this way we defined clinical RA as the reference standard when analyzing the diagnostic accuracy. Blood samples were analyzed for Anti-CCP2 using Immunscan CCPlus (Eurodiagnostica). Cut off set by the manufacture were used to define positive (≥cut off), and high positive (>3x cut off) CCP was defined in accordance to EULAR criteria for RA. All Anti-CCP positive samples were further investigated by ELISA for the presence of antibodies against autoantigen-derived citrullinated peptides (alpha-enolase: aa5-21; collagen type II: aa359-369; fibrinogen: aa563-583 and vimentin: aa60-75). Sensitivity and specificity as well as the positive (PPV) and negative (NPV) predictive values of Anti-CCP testing for detecting prevalent RA were estimated.

Results:

350 out of 12 590 tested individuals (2.8%) were positive for Anti-CCP. 1.5% (192/12590) had prevalent RA with in median 5 years from first occurring RA diagnosis in register to blood donation. Of these RA cases, 65% (124/192) were positive for Anti-CCP and a majority had high concentrations (93%). The rest of those positive for Anti-CCP were without RA diagnosis and fewer had high positive anti-CCP (39%).

The sensitivity and specificity for high positive Anti-CCP testing were 60% (95% CI: 53-67%) and 99% (95% CI: 99%), respectively. Both high positive Anti-CCP and Anti-CCP had a good predictive value for detecting RA (PPV 57%, 95% CI 50-64% for high positive Anti-CCP and 35%, 95% CI 30-40% for Anti-CCP) and a negative predictive values close to 100%.

Anti-CEP1 antibodies were the most common ACPA among Anti-CCP positive RA patients and Anti-CCP positive without RA. There was a correlation between anti-ccp concentration and occurrence other ACPAs (Spearman Correlation Coefficient r= 0.75 p <0.0001). In accordance we found 52% sensitivity for positive anti-CCP2 test and ≥1 other ACPA test positive and 99% specificity, PPV was 56% and the NPV was 99%

Conclusion:

Anti-CCP testing has a good diagnostic accuracy for RA in a large population based cohort. Anti-CCP in high concentration is correlated with presence of other ACPAs in population based cohort. A follow up study to identify new incident cases of RA among tested individuals will allow more accurate estimates in the future.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/diagnostic-accuracy-of-anti-ccp-testing-for-detecting-prevalent-rheumatoid-arthritis-results-from-screening-a-population-based-cohort/