Clinical Rheumatology

, 29:33

Significance of anti-CCP antibodies in modification of 1987 ACR classification criteria in diagnosis of rheumatoid arthritis

  • Jinxia Zhao
  • Xiangyuan Liu
  • Zhimin Wang
  • Zhanguo Li
Original Article


To examine the incorporation of anti-CCP antibodies into the American College of Rheumatology (ACR) classification criteria for rheumatoid arthritis (RA) and to evaluate the advantages of the revised anti-CCP criteria in diagnosing Chinese patients. Patients who suffered from arthritic problems during the recent 2 years were selected from the Department of Rheumatology and Immunology of Peking University People's Hospital. The patients were divided into RA group and non-RA group according to the clinical diagnosis by experienced rheumatologists. The ACR criteria were revised in three ways: (1) replacement of rheumatoid nodules and erosions as criteria with anti-CCP antibodies (RA-6 criteria); (2) replacement of rheumatoid nodules with anti-CCP antibodies as a criterion (RA-7 criteria); (3) addition of anti-CCP antibodies (RA-8 criteria). The diagnostic value of ACR criteria and anti-CCP revised criteria (RA-6, RA-7, and RA-8) were evaluated by comparing the sensitivity and specificity of all criteria, in all subjects and in subjects with arthritis symptoms within 2 years. There were 604 patients included in the study totally, among whom 312 patients were diagnosed as RA and 292 were diagnosed as other rheumatic diseases by rheumatologists. For all the RA patients, the sensitivity and specificity of anti-CCP antibodies were 76.2% and 96%, respectively. Its specificity was much higher than RF (85.2%). For the patients with a disease duration less than two years, the sensitivities were 82.0%, 91.0%, 87.0%, and 87.0%, while the specificities were 95.6%, 83.9%, 95.6%, and 95.6%, respectively, according to 1987 ACR criteria, RA-6, RA-7, and RA-8 criteria. Among all the RA patients, the corresponding sensitivities were 92.3%, 96.8%, 94.6%, and 94.6%, and the specificities were 92.8%, 83.6%, 92.8%, and 92.8%, respectively. The 1987 ACR criteria have high sensitivity and specificity in established RA, but are less sensitive in early RA. The RA-6 criteria improve the sensitivity by reducing its specificity. The RA-7 criteria with replacement of rheumatoid nodules by anti-CCP antibodies increase the sensitivity without losing specificity, which may serve as new classification criteria in routine clinical practice, especially in early RA patients.


American College of Rheumatology Arthritis Classification Cyclic citrullinated peptide Rheumatoid 


  1. 1.
    Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324CrossRefPubMedGoogle Scholar
  2. 2.
    Saraux A, Berthelot JM, Chales G et al (2001) Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later. Arthritis Rheum 44:2485–2491CrossRefPubMedGoogle Scholar
  3. 3.
    Zendman AJ, Vossenaar ER, van Venrooij WJ (2004) Autoantibodies to citrullinated (poly)peptides: a key diagnostic and prognostic marker for rheumatoid arthritis. Autoimmunity 37:295–299CrossRefPubMedGoogle Scholar
  4. 4.
    Liao KP, Batra KL, Chibnik L et al (2008) Anti-CCP revised criteria for the classification of rheumatoid arthritis. Ann Rheum Dis 67(11):1557–1561CrossRefPubMedGoogle Scholar
  5. 5.
    American College of Rheumatology Ad Hoc Committee on Clinical Guidelines (1996) Guidelines for the management of rheumatoid arthritis. Arthritis Rheum 39:713–722CrossRefGoogle Scholar
  6. 6.
    American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines (2002) Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum 46:328–346CrossRefGoogle Scholar
  7. 7.
    Saag KG, Teng GG, Patkar NM et al (2008) American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 59:762–784CrossRefPubMedGoogle Scholar
  8. 8.
    Kaarela K, Kauppi MJ, Lehtinen KE (1995) The value of the ACR 1987 criteria in very early rheumatoid arthritis. Scand J Rheumatol 24:279–281CrossRefPubMedGoogle Scholar
  9. 9.
    Aletaha D, Breedveld FC, Smolen JS (2005) The need for new classification criteria for rheumatoid arthritis. Arthritis Rheum 52:3333–3336CrossRefPubMedGoogle Scholar
  10. 10.
    Mathsson L, Mullazehi M, Wick MC et al (2008) Antibodies against citrullinated vimentin in rheumatoid arthritis: higher sensitivity and extended prognostic value concerning future radiographic progression as compared with antibodies against cyclic citrullinated peptides. Arthritis Rheum 58:36–45CrossRefPubMedGoogle Scholar
  11. 11.
    Hill JA, Al-Bishri J, Gladman DD et al (2006) Serum autoantibodies that bind citrullinated fibrinogen are frequently found in patients with rheumatoid arthritis. J Rheumatol 33:2115–2119PubMedGoogle Scholar
  12. 12.
    Nienhuis RL, Mandema E (1964) A new serum factor in patients with rheumatoid arthritis: the antiperinuclear factor. Ann Rheum Dis 23:302–305CrossRefPubMedGoogle Scholar
  13. 13.
    Scott DL, Delamere JP, Jones LJ et al (1981) Significance of laminar antikeratin antibodies to rat oesophagus in rheumatoid arthritis. Ann Rheum Dis 40:267–271CrossRefPubMedGoogle Scholar
  14. 14.
    Schellekens GA, de Jong BA, van den Hoogen FH et al (1998) Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 101:273–281CrossRefPubMedGoogle Scholar
  15. 15.
    Quinn MA, Gough AK, Green MJ et al (2006) Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome. Rheumatology (Oxford) 45:478–480CrossRefGoogle Scholar
  16. 16.
    Silveira IG, Burlingame RW, von Muhlen CA et al (2007) Anti-CCP antibodies have more diagnostic impact than rheumatoid factor (RF) in a population tested for RF. Clin Rheumatol 26:1883–1889CrossRefPubMedGoogle Scholar
  17. 17.
    Schellekens GA, Visser H, de Jong BA et al (2000) The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43:155–163CrossRefPubMedGoogle Scholar
  18. 18.
    Avouac J, Gossec L, Dougados M (2006) Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis 65:845–851CrossRefPubMedGoogle Scholar
  19. 19.
    van Gaalen FA, Linn-Rasker SP, van Venrooij WJ et al (2004) Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum 50:709–715CrossRefPubMedGoogle Scholar
  20. 20.
    Mimori T (2005) Clinical significance of anti-CCP antibodies in rheumatoid arthritis. Intern Med 44:1122–1126CrossRefPubMedGoogle Scholar
  21. 21.
    Abdel-Nasser AM, Mahmoud MH, El Mansoury TM, Osman AM (2008) Anti-CCP2 is an adjunct to, not a surrogate for, rheumatoid factor in the diagnosis of rheumatoid arthritis: diagnostic utility of anti-CCP2 antibodies in Egyptian patients with rheumatoid arthritis. Scand J Rheumatol 37(5):329–336CrossRefPubMedGoogle Scholar
  22. 22.
    Symmons DP (2007) Classification criteria for rheumatoid arthritis—time to abandon rheumatoid factor? Rheumatology (Oxford) 46(5):725–726CrossRefGoogle Scholar
  23. 23.
    Visser H, le Cessie S, Vos K et al (2002) How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheum 46:357–365CrossRefPubMedGoogle Scholar
  24. 24.
    Carmona L, González-álvaro I, Balsa A et al (2003) Rheumatoid arthritis in Spain: occurrence of extra-articular manifestations and estimates of disease severity. Ann Rheum Dis 62:897–900CrossRefPubMedGoogle Scholar

Copyright information

© Clinical Rheumatology 2009

Authors and Affiliations

  • Jinxia Zhao
    • 1
  • Xiangyuan Liu
    • 1
  • Zhimin Wang
    • 2
  • Zhanguo Li
    • 2
  1. 1.Department of Rheumatology and ImmunologyPeking University Third HospitalBeijingChina
  2. 2.Department of Rheumatology and ImmunologyPeking University People’s HospitalBeijingChina

Personalised recommendations