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Autoantibodies to cyclic citrullinated peptide 2 (CCP2) are superior to other potential diagnostic biomarkers for predicting rheumatoid arthritis in early undifferentiated arthritis

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Abstract

We evaluated the diagnostic value of anti-cyclic citrullinated peptide 2 (anti-CCP2) antibodies and other potential diagnostic biomarkers (IgM rheumatoid factor, anti-agalactosyl IgG antibodies, matrix metalloproteinase 3, C-reactive protein) for predicting early development of rheumatoid arthritis (RA). Patients were defined as having recent-onset undifferentiated arthritis (UA) if they had developed arthritis in two or more joints within the previous 2 years and could not be classified with a well-defined arthropathy. Baseline levels of biomarkers were measured in blood samples collected at the entry of the study and the patients were followed for 1 year to monitor development of RA. Diagnoses of RA and non-RA arthropathies were made according to individual standard diagnostic criteria. A total of 146 patients were enrolled in the study. In the follow-up year, 18 patients developed RA, 54 developed non-RA arthropathies, and 60 remained in the UA category. The sensitivity and specificity of the presence of anti-CCP2 antibodies for the diagnosis of RA were 83.3 and 93.0%, respectively. The positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of anti-CCP2 antibodies for RA (65.2, 97.2, and 91.7%, respectively) were higher than for any other biomarker. Combination of anti-CCP2 with any other biomarker only slightly improved each diagnostic value compared to the presence of anti-CCP2 alone. Among the anti-CCP2-positive patients, the average titer was significantly higher in those with RA than in non-RA or UA patients (163.7 ± 138.4 vs 55.2 ± 72.0 U/ml, p = 0.017). Anti-CCP2 antibodies are superior to any other single biomarker for predicting early development of RA in patients with recent-onset UA and the diagnostic value of anti-CCP2 alone is similar to that for biomarker combinations. Moreover, the anti-CCP2 antibody titer is useful to discriminate between patients at high risk for early developing RA from those at risk of developing non-RA arthropathies.

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Acknowledgments

This work was supported by a Grant-in-Aid for Research on Immunological Disorders from the Japan National Hospital Organization.

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Authors and Affiliations

  1. Department of Clinical Research, NHO Osaka Minami Medical Center, 2-1 Kidohigashimachi, Kawachinagano, Osaka, 586-8521, Japan

    Eriko Kudo-Tanaka, Shiro Ohshima, Masaru Ishii, Yoshinori Katada, Hitomi Ikeue & Yukihiko Saeki

  2. Department of Rheumatology, National Hospital Organization Osaka Minami Medical Center, Osaka, Japan

    Eriko Kudo-Tanaka, Shiro Ohshima, Masaru Ishii, Toru Mima, Masato Matsushita, Mitsuko Umeshita-Sasai & Yukihiko Saeki

  3. National Hospital Organization Osaka Minami Medical Center, Osaka, Japan

    Naoto Azuma, Yoshinori Harada, Yoshinori Katada, Kunio Miyatake & Yukihiko Saeki

Authors
  1. Eriko Kudo-Tanaka
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  2. Shiro Ohshima
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  3. Masaru Ishii
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  9. Hitomi Ikeue
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Correspondence to Yukihiko Saeki.

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Kudo-Tanaka, E., Ohshima, S., Ishii, M. et al. Autoantibodies to cyclic citrullinated peptide 2 (CCP2) are superior to other potential diagnostic biomarkers for predicting rheumatoid arthritis in early undifferentiated arthritis. Clin Rheumatol 26, 1627–1633 (2007). https://doi.org/10.1007/s10067-007-0558-5

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  • DOI: https://doi.org/10.1007/s10067-007-0558-5

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