Skip to main content

Advertisement

SpringerLink
Log in

Anti-CCP antibodies have more diagnostic impact than rheumatoid factor (RF) in a population tested for RF

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

To compare the diagnostic powers of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) in a population selected for its high statistical relevance, over a 6-month period, an informed consent to test for anti-CCP was obtained from 1,025 consecutive patients for whom RF was ordered at a University laboratory. Within 1 year, a diagnosis was obtained without informing the physician about the anti-CCP result. Extensive statistical analyses were performed. A total of 768 patients satisfied the inclusion criteria, and 132 were classified as having RA, yielding a pre-test probability of RA of 17%. The sensitivities for anti-CCP and RF were 62 and 64% (P = 0.83), and the specificities were 97 and 90% (P < 0.001), respectively. The positive predictive value (PPV) was 79% for anti-CCP and 56% for RF (P < 0.001), whereas the negative predictive value was 92% for both. The likelihood ratio (LR) was 17.9 for anti-CCP and 6.2 for RF (P < 0.005). Forty RA patients were diagnosed with RA of less than 2 years length, and the same significant statistic differences between anti-CCP and RF were observed. Placing the results of both tests together, or using different cutoff points, increased the diagnostic utility of the tests. The anti-CCP test has statistically shown significant higher specificity, PPV, and LR for RA than the RF test in a clinically diverse population. If new criteria are to be devised to help diagnose early RA, anti-CCP should be included because it has a greater diagnostic impact than RF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Van der Heijde D (1995) Joint erosions and patients with early rheumatoid arthritis. Br J Rheumatol 34:74–78

    PubMed  Google Scholar 

  2. O’Dell JR (2002) Treating rheumatoid arthritis early: a window of opportunity? Arthritis Rheum 46:283–285

    Article  PubMed  Google Scholar 

  3. Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  PubMed  CAS  Google Scholar 

  4. Ostergaard M, Ejbjerg B, Szkudlarek M (2005) Imaging in early rheumatoid arthritis: roles of magnetic resonance imaging, ultrasonography, conventional radiography and computed tomography. Best Pract Res Clin Rheumatol 19:91–116

    Article  PubMed  Google Scholar 

  5. Schumacher HR, Pessler F, Chen LX (2003) Diagnosing early rheumatoid arthritis (RA). What are the problems and opportunities? Clin Exp Rheumatol 21(5 Suppl 31):S15–S19

    PubMed  CAS  Google Scholar 

  6. Goldbach-Mansky R, Lee J, McCoy A et al (2000) Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset. Arthritis Res 2(3):236–243

    Article  PubMed  CAS  Google Scholar 

  7. 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(1):273–281

    PubMed  CAS  Google Scholar 

  8. Nienhuis RL, Mandema E (1964) A new serum factor in patients with rheumatoid arthritis; the antiperinuclear factor. Ann Rheum Dis 23:302–305

    PubMed  CAS  Google Scholar 

  9. Young BJ, Mallya RK, Leslie RD et al (1979) Anti-keratin antibodies in rheumatoid arthritis. Br Med J 2(6182):97–99

    Article  PubMed  CAS  Google Scholar 

  10. Silveira IG, Keiserman MW, vonMühlen CA (2000) Clinical and laboratorial study of antiperinuclear factor in rheumatoid arthritis. Rev Bras Reumatol 40:159–167

    Google Scholar 

  11. Sebbag M, Simon M, Vincent C et al (1995) The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies. J Clin Invest 95(6):2672–2679

    PubMed  CAS  Google Scholar 

  12. Simon M, Girbal E, Sebbag M et al (1993) The cytokeratin filament-aggregating protein filaggrin is the target of the so-called “antikeratin antibodies,” autoantibodies specific for rheumatoid arthritis. J Clin Invest 92(3):1387–1393

    PubMed  CAS  Google Scholar 

  13. Girbal-Neuhauser E, Durieux JJ, Arnaud M et al (1999) The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deimination of arginine residues. J Immunol 162(1):585–594

    PubMed  CAS  Google Scholar 

  14. Union A, Meheus L, Humbel RL et al (2002) Identification of citrullinated rheumatoid arthritis-specific epitopes in natural filaggrin relevant for antifilaggrin autoantibody detection by line immunoassay. Arthritis Rheum 46(5):1185–1195

    Article  PubMed  CAS  Google Scholar 

  15. Serre G (2001) Autoantibodies to filaggrin/deiminated fibrin (AFA) are useful for the diagnosis and prognosis of rheumatoid arthritis, and are probably involved in the pathophysiology of the disease. Joint Bone Spine 68(2):103–105

    Article  PubMed  CAS  Google Scholar 

  16. Dubucquoi S, Solau-Gervais E, Lefranc D et al (2004) Evaluation of anti-citrullinated filaggrin antibodies as hallmarks for the diagnosis of rheumatic diseases. Ann Rheum Dis 63(4):415–419

    Article  PubMed  CAS  Google Scholar 

  17. Grootenboer-Mignot S, Nicaise-Roland P, Delaunay C et al (2004) Second generation anti-cyclic citrullinated peptide (anti-CCP2) antibodies can replace other anti-filaggrin antibodies and improve rheumatoid arthritis diagnosis. Scand J Rheumatol 33(4):218–220

    Article  PubMed  CAS  Google Scholar 

  18. De Rycke L, Peene I, Hoffman IE et al (2004) Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations. Ann Rheum Dis 63(12):1587–1593

    Article  PubMed  CAS  Google Scholar 

  19. 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(1):155–163

    Article  PubMed  CAS  Google Scholar 

  20. Bas S, Perneger TV, Seitz M et al (2002) Diagnostic tests for rheumatoid arthritis: comparison of anti-cyclic citrullinated peptide antibodies, anti-keratin antibodies and IgM rheumatoid factors. Rheumatology (Oxford) 41(7):809–814

    Article  CAS  Google Scholar 

  21. Bizzaro N, Mazzanti G, Tonutti E et al (2001) Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis. Clin Chem 47(6):1089–1093

    PubMed  CAS  Google Scholar 

  22. Sauerland U, Becker H, Seidel M et al (2005) Clinical utility of the anti-CCP assay: experiences with 700 patients. Ann N Y Acad Sci 1050:314–318

    Article  PubMed  CAS  Google Scholar 

  23. Ronnelid J, Wick MC, Lampa J et al (2005) Longitudinal analysis of anti-citrullinated protein/peptide antibodies (anti-CP) during 5 year follow-up in early rheumatoid arthritis: anti-CP status is a stable phenotype that predicts worse disease activity and greater radiological progression. Ann Rheum Dis 64(12):1744–1749

    Article  PubMed  CAS  Google Scholar 

  24. Kroot EJ, de Jong BA, van Leeuwen MA et al (2000) The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum 43(8):1831–1835

    Article  PubMed  CAS  Google Scholar 

  25. Solanki K, Spellerberg M, Chapman P et al (2004) Anti-cyclic citrullinated antibodies: complementary to IgM rheumatoid factor in the early diagnosis of rheumatoid arthritis. N Z Med J 117(1203):U1097

    PubMed  Google Scholar 

  26. Moons KG, Biesheuvel CJ, Grobbee DE (2004) Test research versus diagnostic research. Clin Chem 50(3):473–476

    Article  PubMed  CAS  Google Scholar 

  27. Deeks JJ, Altman DG (2004) Diagnostic tests 4: likelihood ratios. BMJ 329(7458):168–169

    Article  PubMed  Google Scholar 

  28. Wolfe F (1998) A comparison of IgM rheumatoid factor by nephelometry and latex methods: clinical and laboratory significance. Arthritis Care Res 11(2):89–93

    Article  PubMed  CAS  Google Scholar 

  29. Knight RK, Pritchard MH (1982) Nephelometry compared with differential antibody titre in routine rheumatoid factor measurements. Ann Rheum Dis 41(4):426–430

    PubMed  CAS  Google Scholar 

  30. Sackett DL, Haynes RB, Tugwell P (1985) Clinical epidemiology: a basic science for clinical medicine. Little, Brown & Co, Boston

    Google Scholar 

  31. Gallagher EJ (1998) Clinical utility of likelihood ratios. Ann Emerg Med 31(3):391–397

    Article  PubMed  CAS  Google Scholar 

  32. Radack KL, Rouan G, Hedges J (1986) The likelihood ratio. An improved measure for reporting and evaluating diagnostic test results. Arch Pathol Lab Med 110(8):689–693

    PubMed  CAS  Google Scholar 

  33. Wolfe F, Cathey MA, Roberts FK (1991) The latex test revisited. Rheumatoid factor testing in 8,287 rheumatic disease patients. Arthritis Rheum 34(8):951–960

    Article  PubMed  CAS  Google Scholar 

  34. Visser H, Gelinck LB, Kampfraath AH et al (1996) Diagnostic and prognostic characteristics of the enzyme linked immunosorbent rheumatoid factor assays in rheumatoid arthritis. Ann Rheum Dis 55(3):157–161

    Article  PubMed  CAS  Google Scholar 

  35. Rantapaa-Dahlqvist S, de Jong BA, Berglin E et al (2003) Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 48(10):2741–2749

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rheumatology Department, Sao Lucas Hospital, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil

    I. G. Silveira, C. A. von Mühlen, A. L. Bender & H. L. Staub

  2. INOVA Diagnostics, San Diego, CA, USA

    R. W. Burlingame

Authors
  1. I. G. Silveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. W. Burlingame
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. A. von Mühlen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. L. Bender
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. L. Staub
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. G. Silveira.

Appendix

Appendix

Appendix 1

Appendix 2

Table 8 Demographic, clinical and laboratorial characteristics of 940 patients, divided in three groups: studied group (768 patients), excluded patients with no diagnosis (151 patients) and excluded patients with undefined diagnosis of rheumatoid arthritis (21 patients)
Full size table

Rights and permissions

Reprints and permissions

About this article

Cite this article

Silveira, I.G., Burlingame, R.W., von Mühlen, C.A. et al. Anti-CCP antibodies have more diagnostic impact than rheumatoid factor (RF) in a population tested for RF. Clin Rheumatol 26, 1883–1889 (2007). https://doi.org/10.1007/s10067-007-0601-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-007-0601-6

Keywords

Search

Navigation