Skip to main content
Log in

Diagnostic accuracy of anti-MCV and anti-CCP antibodies in rheumatoid arthritis

A meta-analysis

Diagnostische Genauigkeit von Anti-MCV- und Anti-CCP-Antikörpern bei rheumatoider Arthritis

Eine Metaanalyse

  • Originalien
  • Published:
Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Abstract

Objective

The purpose of this study was to compare the diagnostic performance of anti-mutated citrullinated vimentin (anti-MCV) and anti-cyclic citrullinated peptide (anti-CCP) antibodies in rheumatoid arthritis (RA).

Methods

We searched the Medline, Embase, and Cochrane library databases and performed two meta-analyses on the diagnostic accuracy of anti-MCV and anti-CCP in patients with RA compared to healthy controls.

Results

We identified 12 studies that included a total of 2003 RA patients and 831 healthy controls for the meta-analysis. The pooled sensitivity and specificity of anti-MCV were 68.6 % [95 % confidence interval (CI) 66.6–79.7] and 94.2 % (95 % CI 92.4–96.7) and those of anti-CCP were 61.7 % (95 % CI 59.5–63.8) and 97.1 % (95 % CI 96.7–98.1), respectively. Anti-MCV PLR, NLR, and DOR were 12.99 (95 % CI 8.013–21.27), 0.297 (95 % CI 0.238–0.369), and 47.78 (95 % CI 28.59–79.84), and those for anti-CCP were 16.71 (95 % CI 11.42–24.47), 0.378 (95 % CI 0.325–0.439), and 54.20 (95 % CI 31.65–92.82), respectively. The AUC of anti-MCV was 0.886, and its Q* index was 0.817, indicating modest accuracy, while the AUC of anti-CCP was 0.946, and its Q* index was 0.885. The sensitivity of anti-MCV was significantly higher than that of anti-CCP in the diagnosis of RA (difference 0.069, 95 % CI 0.039–0.098, p < 0.0001), but the specificity of anti-MCV was lower than that of anti-CCP (difference − 0.029, 95 % CI − 0.051 to − 0.006, p = 0.012). The Q* index of anti-MCV was significantly lower than that of anti-CCP (difference − 0.068, 95 % CI − 0.070 to − 0.065, p < 0.0001).

Conclusion

Our meta-analysis demonstrates that anti-MCV is more sensitive but less specific, and has lower diagnostic accuracy than anti-CCP in RA, although anti-MCV and anti-CCP showed comparable high PLRs.

Zusammenfassung

Zielsetzung

Ziel dieser Studie war es, die diagnostische Leistung von Antikörpern gegen mutiertes citrulliniertes Vimentin (Anti-MCV) und zyklisches citrulliniertes Peptid (Anti-CCP) bei rheumatoider Arthritis (RA) zu vergleichen.

Methoden

Wir durchsuchten die Medline-, Embase- und Cochrane-Datenbanken und führten zwei Metaanalysen bezüglich der diagnostischen Genauigkeit von Anti-MCV- und Anti-CCP-Antikörpern bei Patienten mit RA im Vergleich mit einer gesunden Kontrollgruppe durch.

Ergebnisse

Für die Metaanalyse identifizierten wir 12 Studien, die insgesamt 2003 RA-Patienten sowie 831 Personen in den Kontrollgruppen einschlossen. Die gepoolte Sensitivität und Spezifität von Anti-MCV lag bei 68,6 % [95 % Konfidenzintervall (CI) 66,6–79,7] und 94,2 % (95 % CI 92,4–96,7), die von Anti-CCP bei 61,7 % (95 % CI 59,5–63,8) und 97,1 % (95 % CI 96,7–98,1). PLR-, NLR- und DOR-Werte betrugen für Anti-MCV 12,99 % (95 % CI 8,013–21,27), 0,297 (95 % CI 0,238–0,369) sowie 47,78 (95 % CI 28,59–79,84) und für Anti-CCP 16,71 (95 % CI 11,42–24,47), 0,378 (95 % CI 0,325–0,439) sowie 54,20 (95 % CI 31,65–92,82). Die AUC von Anti-MCV lag bei 0,886 mit einem Q-Index von 0,817, was eine moderate Genauigkeit zeigt, während die AUC von Anti-CCP 0,946 betrug mit einem Q-Index von 0,885. Für die Diagnose von RA war die Sensitivität von Anti-MCV signifikant höher als die von Anti-CCP (Differenz: 0,069, 95 % CI 0,039–0,098; p < 0.0001), die Spezifität von Anti-MCV war jedoch geringer als die von Anti-CCP (Differenz: − 0,029, 95 % CI − 0,051 bis − 0,006; p = 0,012). Der Q-Index von Anti-MCV war signifikant geringer als der von Anti-CCP (Differenz: − 0,068, 95 % CI − 0,070 bis − 0,065, p < 0,0001).

Schlussfolgerung

Unsere Metaanalyse zeigt, dass Anti-MCV eine höhere Sensitivität, aber eine geringere Spezifität als Anti-CCP besitzen und bei der Diagnose von RA eine geringere Genauigkeit aufweisen, obwohl Anti-MCV und Anti-CCP vergleichbar hohe PLR-Werte zeigten.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Lee DM, Weinblatt ME (2001) Rheumatoid arthritis. Lancet 358(9285):903–911

    Article  CAS  PubMed  Google Scholar 

  2. Lard LR, Visser H, Speyer I et al (2001) Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med 111(6):446–451

    Article  CAS  PubMed  Google Scholar 

  3. Dorner T, Egerer K, Feist E, Burmester GR (2004) Rheumatoid factor revisited. Curr Opin Rheumatol 16(3):246–253

    Article  CAS  PubMed  Google Scholar 

  4. Schellekens GA, Jong BA de, Hoogen FH van den et al (1998) Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 101(1):273–281

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Boekel MA van, Vossenaar ER, Hoogen FH van den, Venrooij WJ van (2002) Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Res 4(2):87–93

    Article  PubMed Central  PubMed  Google Scholar 

  6. Vossenaar ER, Zendman AJ, Venrooij WJ van, Pruijn GJ (2003) PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. Bioessays 25(11):1106–1118

    Article  CAS  PubMed  Google Scholar 

  7. Schellekens GA, Visser H, Jong BA de et al (2000) The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43(1):155–163

    Article  CAS  PubMed  Google Scholar 

  8. Mor-Vaknin N, Punturieri A, Sitwala K, Markovitz DM (2003) Vimentin is secreted by activated macrophages. Nat Cell Biol 5(1):59–63

    Article  CAS  PubMed  Google Scholar 

  9. Bang H, Egerer K, Gauliard A et al (2007) Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum 56(8):2503–2511

    Article  CAS  PubMed  Google Scholar 

  10. Vossenaar ER, Despres N, Lapointe E et al (2004) Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthritis Res Ther 6(2):R142–R150

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Hueber W, Hassfeld W, Smolen JS, Steiner G (1999) Sensitivity and specificity of anti-Sa autoantibodies for rheumatoid arthritis. Rheumatology (Oxford) 38(2):155–159

  12. Luime JJ, Colin EM, Hazes JM, Lubberts E (2010) Does anti-mutated citrullinated vimentin have additional value as a serological marker in the diagnostic and prognostic investigation of patients with rheumatoid arthritis? A systematic review. Ann Rheum Dis 69(2):337–344

    Article  CAS  PubMed  Google Scholar 

  13. Zhu T, Feng L (2013) Comparison of anti-mutated citrullinated vimentin, anti-cyclic citrullinated peptides, anti-glucose-6-phosphate isomerase and anti-keratin antibodies and rheumatoid factor in the diagnosis of rheumatoid arthritis in Chinese patients. Int J Rheum Dis 16(2):157–161

    Article  CAS  PubMed  Google Scholar 

  14. Al-Shukaili A, Al-Ghafri S, Al-Marhoobi S, Alkaabi J (2012) Evaluation of anti-mutated citrullinated vimentin antibodies, anti-cyclic citrullinated Peptide antibodies and rheumatoid factor in omani patients with rheumatoid arthritis. Int J Rheumatol 2012:285854

    Article  PubMed Central  PubMed  Google Scholar 

  15. Damjanovska L, Thabet MM, Levarth EW et al (2010) Diagnostic value of anti-MCV antibodies in differentiating early inflammatory arthritis. Ann Rheum Dis 69(4):730–732

    Article  CAS  PubMed  Google Scholar 

  16. Mutlu N, Bicakcigil M, Tasan DA et al (2009) Comparative performance analysis of 4 different anti-citrullinated protein assays in the diagnosis of rheumatoid arthritis. J Rheumatol 36(3):491–500

    Article  PubMed  Google Scholar 

  17. 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(1):36–45

    Article  CAS  PubMed  Google Scholar 

  18. Diaz-Toscano ML, Olivas-Flores EM, Zavaleta-Muniz SA et al (2014) Comparison of two assays to determine anti-citrullinated peptide antibodies in rheumatoid arthritis in relation to other chronic inflammatory rheumatic diseases: assaying anti-modified citrullinated vimentin antibodies adds value to second-generation anti-citrullinated cyclic peptides testing. Biomed Res Int 2014:198198

    Article  PubMed Central  PubMed  Google Scholar 

  19. El-Barbary AM, Kassem EM, El-Sergany MA et al (2011) Association of anti-modified citrullinated vimentin with subclinical atherosclerosis in early rheumatoid arthritis compared with anti-cyclic citrullinated peptide. J Rheumatol 38(5):828–834

    Article  CAS  PubMed  Google Scholar 

  20. Liu X, Jia R, Zhao J, Li Z (2009) The role of anti-mutated citrullinated vimentin antibodies in the diagnosis of early rheumatoid arthritis. J Rheumatol 36(6):1136–1142

    Article  CAS  PubMed  Google Scholar 

  21. Innala L, Kokkonen H, Eriksson C et al (2008) Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides. J Rheumatol 35(6):1002–1008

    PubMed  Google Scholar 

  22. Soos L, Szekanecz Z, Szabo Z et al (2007) Clinical evaluation of anti-mutated citrullinated vimentin by ELISA in rheumatoid arthritis. J Rheumatol 34(8):1658–1663

    CAS  PubMed  Google Scholar 

  23. Nicaise Roland P, Grootenboer Mignot S, Bruns A et al (2008) Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy. Arthritis Res Ther 10(6):R142

    Article  Google Scholar 

  24. Song JS, Park GB, Park AJ (2007) Comparison of anti-mutated citrullinated vimentin with anti-cyclic citrullinated peptide and rheumatoid factors for the diagnostic value of rheumatoid arthritis. Korean Rheum Assoc 14:235–241

    Article  Google Scholar 

  25. Lee YH, Bae SC, Choi SJ et al (2011) Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep 38(6):3643–3651

    Article  CAS  PubMed  Google Scholar 

  26. Lee YH, Rho YH, Choi SJ et al (2006) Association of TNF-alpha − 308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis. Rheumatol Int 27(2):157–161

    Article  CAS  PubMed  Google Scholar 

  27. Lee YH, Rho YH, Choi SJ et al (2007) PADI4 polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Rheumatol Int 27(9):827–833

    Article  CAS  PubMed  Google Scholar 

  28. Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097

    Article  PubMed Central  PubMed  Google Scholar 

  29. Whiting P, Rutjes AW, Reitsma JB et al (2003) The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 3:25

    Article  PubMed Central  PubMed  Google Scholar 

  30. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  31. Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315(7121):1533–1537

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  33. Lijmer JG, Bossuyt PM, Heisterkamp SH (2002) Exploring sources of heterogeneity in systematic reviews of diagnostic tests. Stat Med 21(11):1525–1537

    Article  PubMed  Google Scholar 

  34. Walter SD (2002) Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data. Stat Med 21(9):1237–1256

    Article  CAS  PubMed  Google Scholar 

  35. Zamora J, Abraira V, Muriel A et al (2006) Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 6:31

    Article  PubMed Central  PubMed  Google Scholar 

  36. Besada E, Nikolaisen C, Nossent JC (2011) Diagnostic value of antibodies against mutated citrullinated vimentin for rheumatoid arthritis. Clin Exp Rheumatol 29(1):85–88

    PubMed  Google Scholar 

  37. Dejaco C, Klotz W, Larcher H et al (2006) Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis. Arthritis Res Ther 8(4):R119

    Article  PubMed Central  PubMed  Google Scholar 

  38. Ursum J, Nielen MM, Schaardenburg DV et al (2008) Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study. Arthritis Res Ther 10(1):R12

    Article  PubMed Central  PubMed  Google Scholar 

  39. Wagner E, Skoumal M, Bayer P, Klaushofer K (2009) Antibody against mutated citrullinated vimentin: a new sensitive marker in the diagnosis of rheumatoid arthritis. Rheumatol Int 29(11):1315–1321

    Article  CAS  PubMed  Google Scholar 

  40. Yousefghahari B, Alhooei S, Soleimani-amiri MJ, Guran A (2013) Comparison of sensitivity and specificity of anti-CCP and anti-MCV antibodies in an Iranian cohort of patients with rheumatoid arthritis. Caspian J Intern Med 4(3):702

    PubMed Central  PubMed  Google Scholar 

  41. Maraina CHC, Nurdayana AK, Rusni D, Azwany Y (2010) Diagnostic value of anti‐modified citrullinated vimentin in rheumatoid arthritis. Int J Rheum Dis 13(4):335–339

    Article  PubMed  Google Scholar 

  42. Bartoloni E, Alunno A, Bistoni O et al (2012) Diagnostic value of anti-mutated citrullinated vimentin in comparison to anti-cyclic citrullinated peptide and anti-viral citrullinated peptide 2 antibodies in rheumatoid arthritis: an Italian multicentric study and review of the literature. Autoimmun Rev 11(11):815–820

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported in part by a grant of the Korea Healthcare technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI13C2124).

Compliance with ethical guidelines

Conflict of interest. Y.H. Lee, S.-C. Bae, and G.G. Song state that there are no conflicts of interest.

The accompanying manuscript does not include studies on humans or animals.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Y.H. Lee MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, ., Bae, SC. & Song, G. Diagnostic accuracy of anti-MCV and anti-CCP antibodies in rheumatoid arthritis. Z Rheumatol 74, 911–918 (2015). https://doi.org/10.1007/s00393-015-1598-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-015-1598-x

Keywords

Schlüsselwörter

Navigation