Diagnostic and predictive value of anti-CCP (cyclic citrullinated protein) antibodies in rheumatoid arthritis: a systematic literature review

Jérôme Avouac ¹, Laure Gossec ¹ and Maxime Dougados ^1*

¹ Rhumatologie B, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France

^* To whom correspondence should be addressed. E-mail: maxime.dougados{at}cch.aphp.fr.

Accepted 2 April 2006

Abstract

Objective: To evaluate the two generations of anti-CCP (cyclic citrullinated protein) antibodies as a diagnostic marker of rheumatoid arthritis (RA) and as a predictor of future development of RA in healthy individuals and in patients with early undifferentiated arthritis.

Methods: a systematic analysis of the literature published between 1999 and February 2006 was conducted. Data were collected regarding the sensitivity and specificity of the 2 generations of anti-CCP antibodies to diagnose RA and to predict future development of RA.

Results: among the 107 studies initially identified, 68 had interpretable data and were analyzed. Diagnostic properties were assessed in 58 studies; mean ± standard deviation, SD sensitivity was 53 ±10% (range: 41-68%) and 68 ± 15% (range: 39-94%) for anti- CCP1 and 2 respectively, mean ± SD specificity was 96 ± 3% (range: 90-99%) and 95 ± 5% (range: 81-100%) for anti- CCP1 and 2 respectively. Predictive properties were assessed in 14 studies; odds ratios of anti-CCP1 and 2 for the future development of RA were 20 (95% confidence interval, CI: 14-31) and 25 (95% confidence interval, CI: 18-35) respectively among patients with early undifferentiated arthritis and 64.5 (95% CI: 8.5-489) and 28 (95% CI: 8-95) respectively among healthy individuals.

Conclusion: Sensitivity of the second generation of anti-CCP is close to that of rheumatoid factor, with a higher specificity, to distinguish RA from other rheumatic diseases. Moreover, anti-CCP antibodies appear to be highly predictive of the future development of RA in both healthy individuals and patients with undifferentiated arthritis.

Keywords: anti-CCP antibodies, diagnosis, predictive marker, rheumatoid arthritis, serological marker

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