Skip to main content

Advertisement

SpringerLink
Log in

Anti-MCV antibodies predict radiographic progression in Greek patients with very early (<3 months duration) rheumatoid arthritis

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

Abstract

This study aimed to assess the diagnostic and prognostic value of anti-mutated citrullinated vimentin (MCV) antibodies in very early rheumatoid arthritis (VERA) and in established rheumatoid arthritis (RA). Seventy-one patients with undifferentiated arthritis (UA) of <3 months duration, 141 with established RA, 53 with other rheumatic diseases, and 40 healthy individuals were included in the study. Anti-MCV, anti-cyclic citrullinated peptide (CCP) antibodies, and rheumatoid factor (RF) were determined and hand radiographs were recorded. Patients were assessed prospectively for 2 years, and hand radiographs were repeated. Diagnostic performance of anti-MCV was studied with receiver operating characteristic (ROC) curves and evaluation of sensitivity, specificity, and likelihood ratios. Forty-six percent of UA patients progressed to RA at 2 years. In VERA patients, sensitivity of anti-MCV was 52 %, compared to 44 % of anti-CCP and 37 % of RF, while specificity was 91 %, compared to 91 % of RF and 84 % of anti-CCP. Anti-MCV were detected in 25 % of VERA patients negative for both anti-CCP and RF. In established RA, anti-MCV did not sustain its diagnostic performance. By multivariable analysis, anti-MCV, but not anti-CCP or RF, showed significant correlation with radiographic progression in VERA patients. In established RA, anti-MCV, anti-CCP, and RF were associated with active disease (p ≤ 0.03) and joint damage (p ≤ 0.004). By multivariate analysis, the strongest factors for radiographic damage were disease duration (p = 0.000), HAQ score (p = 0.000), and RF (p = 0.002). In conclusion, in patients with very early UA, anti-MCV predict both progression to RA and radiological damage, and therefore, anti-MCV antibody testing may be useful in every day practice.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Scott DL (2004) Radiological progression in established rheumatoid arthritis. J Rheumatol Suppl 69:55–65

    PubMed  Google Scholar 

  2. Sakkas LI, Bogdanos DP, Katsiari CG, Platsoucas CD (2014) Anti-citrullinated peptides as autoantigens in rheumatoid arthritis—relevance to treatment. Autoimmun Rev 13:1114–1120. doi:10.1016/j.autrev.2014.08.012

    Article  CAS  PubMed  Google Scholar 

  3. Syversen SW, Gaarder PI, Goll GL, Ødegård S, Haavardsholm EA, Mowinckel P, van der Heijde D, Landewé R, Kvien TK (2008) High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis 67(2):212–217

    Article  CAS  PubMed  Google Scholar 

  4. Turesson C, Jacobsson LT, Sturfelt G, Matteson EL, Mathsson L, Rönnelid J (2007) Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis. Ann Rheum Dis 66(1):59–64

    Article  CAS  PubMed  Google Scholar 

  5. Alexiou I, Germenis A, Koutroumpas A, Kontogianni A, Theodoridou K, Sakkas LI (2008) Anti-cyclic citrullinated peptide-2 (CCP2) autoantibodies and extra-articular manifestations in Greek patients with rheumatoid arthritis. Clin Rheumatol 27(4):511–513. doi:10.1007/s10067-007-0800-1

    Article  PubMed  Google Scholar 

  6. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69(9):1580–1588. doi:10.1136/ard.2010.138461

    Article  PubMed  Google Scholar 

  7. Conrad K, Roggenbuck D, Reinhold D, Dörner T (2010) Profiling of rheumatoid arthritis associated autoantibodies. Autoimmun Rev 9(6):431–435. doi:10.1016/j.autrev.2009.11.017

    Article  CAS  PubMed  Google Scholar 

  8. Vossenaar ER, Després N, Lapointe E, van der Heijden A, Lora M, Senshu T, van Venrooij WJ, Ménard HA (2004) Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthritis Res Ther 6(2):R142–R150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bang H, Egerer K, Gauliard A, Lüthke K, Rudolph PE, Fredenhagen G, Berg W, Feist E, Burmester GR (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. Mathsson L, Mullazehi M, Wick MC, Sjöberg O, van Vollenhoven R, Klareskog L, Rönnelid J (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. doi:10.1002/art.23188

    Article  CAS  PubMed  Google Scholar 

  11. Nicaise Roland P, Grootenboer Mignot S, Bruns A, Hurtado M, Palazzo E, Hayem G, Dieudé P, Meyer O, Chollet Martin S (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. doi:10.1186/ar2570

    Article  PubMed  PubMed Central  Google Scholar 

  12. Raza K, Mathsson L, Buckley CD, Filer A, Rönnelid J (2010) Anti-modified citrullinated vimentin (MCV) antibodies in patients with very early synovitis. Ann Rheum Dis 69(3):627–628. doi:10.1136/ard.2009.118448

    Article  CAS  PubMed  Google Scholar 

  13. Bartoloni E, Alunno A, Bistoni O, Bizzaro N, Migliorini P, Morozzi G, Doria A, Mathieu A, Lotzniker M, Allegri F, Riccieri V, Alpini C, Gabrielli A, Tampoia M, Gerli R, Forum Interdisciplinare per la Ricerca nelle Malattie Autoimmuni (FIRMA) investigators (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. doi:10.1016/j.autrev.2012.02.015

    Article  CAS  PubMed  Google Scholar 

  14. Larsen A (1995) How to apply Larsen score in evaluating radiographs of rheumatoid arthritis in long-term studies. J Rheumatol 22(10):1974–1975

    CAS  PubMed  Google Scholar 

  15. Juarez M, Bang H, Hammar F, Reimer U, Dyke B, Sahbudin I, Buckley CD, Fisher B, Filer A, Raza K (2016) Identification of novel antiacetylated vimentin antibodies in patients with early inflammatory arthritis. Ann Rheum Dis 75(6):1099–1107. doi:10.1136/annrheumdis-2014-206785

    Article  CAS  PubMed  Google Scholar 

  16. Svärd A, Kastbom A, Söderlin MK, Reckner-Olsson Å, Skogh T (2011) A Comparison between IgG- and IgA-class antibodies to cyclic citrullinated peptides and to modified citrullinated vimentin in early rheumatoid arthritis and very early arthritis. J Rheumatol 38(7):1265–1272. doi:10.3899/jrheum.101086

    Article  PubMed  Google Scholar 

  17. van der Linden MP, van der Woude D, Ioan-Facsinay A, Levarht EW, Stoeken-Rijsbergen G, Huizinga TW, Toes RE, van der Helm-van Mil AH (2009) Value of anti-modified citrullinated vimentin and third-generation anti-cyclic citrullinated peptide compared with second-generation anti-cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis. Arthritis Rheum 60(8):2232–2241. doi:10.1002/art.24716

    Article  PubMed  Google Scholar 

  18. Sizova L (2012) Diagnostic value of antibodies to modified citrullinated vimentin in early rheumatoid arthritis. Hum Immunol 73(4):389–392. doi:10.1016/j.humimm.2012.01.007

    Article  CAS  PubMed  Google Scholar 

  19. 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. doi:10.3899/jrheum.080796

    Article  CAS  PubMed  Google Scholar 

  20. El-Barbary AM, Kassem EM, El-Sergany MA, Essa SA, Eltomey MA (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. doi:10.3899/jrheum.101143

    Article  CAS  PubMed  Google Scholar 

  21. Innala L, Kokkonen H, Eriksson C, Jidell E, Berglin E, Dahlqvst SR (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. 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. doi:10.1136/ard.2008.103283

    Article  CAS  PubMed  Google Scholar 

  23. Mansour HE, Metwaly KM, Hassan IA, Elshamy HA, Elbeblawy MM (2010) Antibodies to mutated citrullinated vimentin in rheumatoid arthritis: diagnostic value, association with radiological damage and axial skeleton affection. Clin Med Insights Arthritis Musculoskelet Disord 3:33–42

    Article  PubMed  PubMed Central  Google Scholar 

  24. 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):702–706

    PubMed  PubMed Central  Google Scholar 

  25. Díaz-Toscano ML, Olivas-Flores EM, Zavaleta-Muñiz SA, Gamez-Nava JI, Cardona-Muñoz EG, Ponce-Guarneros M, Castro-Contreras U, Nava A, Salazar-Paramo M, Celis A, Fajardo-Robledo NS, Corona-Sanchez EG, Gonzalez-Lopez L (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. doi:10.1155/2014/198198

    Article  PubMed  PubMed Central  Google Scholar 

  26. Coenen D, Verschueren P, Westhovens R, Bossuyt X (2007) Technical and diagnostic performance of 6 assays for the measurement of citrullinated protein/peptide antibodies in the diagnosis of rheumatoid arthritis. Clin Chem 53(3):498–504

    Article  CAS  PubMed  Google Scholar 

  27. Ursum J, Nielen MM, van Schaardenburg D, van der Horst AR, van de Stadt RJ, Dijkmans BA, Hamann D (2008) Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study. Arthritis Res Ther 10(1):R12. doi:10.1186/ar2362

    Article  PubMed  PubMed Central  Google Scholar 

  28. Dejaco C, Klotz W, Larcher H, Duftner C, Schirmer M, Herold M (2006) Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis. Arthritis Res Ther 8(4):R119

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sghiri R, Bouajina E, Bargaoui D, Harzallah L, Fredj HB, Sammoud S, Ghedira I (2008) Value of anti-mutated citrullinated vimentin antibodies in diagnosing rheumatoid arthritis. Rheumatol Int 29(1):59–62. doi:10.1007/s00296-008-0614-8

    Article  CAS  PubMed  Google Scholar 

  30. Mutlu N, Bicakcigil M, Tasan DA, Kaya A, Yavuz S, Ozden AI (2009) Comparative performance analysis of 4 different anti-citrullinated protein assays in the diagnosis of rheumatoid arthritis. J Rheumatol 36(3):491–500. doi:10.3899/jrheum.080656

    Article  PubMed  Google Scholar 

  31. Szekanecz Z, Szabó Z, Zeher M, Soós L, Dankó K, Horváth I, Lakos G (2013) Superior performance of the CCP3.1 test compared to CCP2 and MCV in the rheumatoid factor-negative RA population. Immunol Res 56(2–3):439–443. doi:10.1007/s12026-013-8425-8

    Article  CAS  PubMed  Google Scholar 

  32. Shidara K, Inoue E, Tanaka E, Hoshi D, Seto Y, Nakajima A, Momohara S, Taniguchi A, Yamanaka H (2011) Comparison of the second and third generation anti-cyclic citrullinated peptide antibody assays in the diagnosis of Japanese patients with rheumatoid arthritis. Rheumatol Int 31(5):617–622. doi:10.1007/s00296-009-1336-2

    Article  CAS  PubMed  Google Scholar 

  33. Sokolove J, Bromberg R, Deane KD, Lahey LJ, Derber LA, Chandra PE, Edison JD, Gilliland WR, Tibshirani RJ, Norris JM, Holers VM, Robinson WH (2012) Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS One 7(5):e35296. doi:10.1371/journal.pone.0035296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Meyer LH, Franssen L, Pap T (2006) The role of mesenchymal cells in the pathophysiology of inflammatory arthritis. Best Pract Res Clin Rheumatol 20(5):969–981

    Article  CAS  PubMed  Google Scholar 

  35. Kastbom A, Forslind K, Ernestam S, Geborek P, Karlsson JA, Petersson IF, Saevarsdottir S, Klareskog L, van Vollenhoven RF, Lundberg K (2016) Changes in the anticitrullinated peptide antibody response in relation to therapeutic outcome in early rheumatoid arthritis: results from the SWEFOT trial. Ann Rheum Dis 75(2):356–361. doi:10.1136/annrheumdis-2014-205698

    Article  CAS  PubMed  Google Scholar 

  36. de Rooy DP, van der Linden MP, Knevel R, Huizinga TW, van der Helm-van Mil AH (2011) Predicting arthritis outcomes—what can be learned from the Leiden Early Arthritis Clinic? Rheumatology 50(1):93–100. doi:10.1093/rheumatology/keq230

    Article  PubMed  Google Scholar 

  37. Boire G, Cossette P, de Brum-Fernandes AJ, Liang P, Niyonsenga T, Zhou ZJ, Carrier N, Daniel C, Ménard HA (2005) Anti-Sa antibodies and antibodies against cyclic citrullinated peptide are not equivalent as predictors of severe outcomes in patients with recent-onset polyarthritis. Arthritis Res Ther 7(3):R592–R603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Degboé Y, Constantin A, Nigon D, Tobon G, Cornillet M, Schaeverbeke T, Chiocchia G, Nicaise-Roland P, Nogueira L, Serre G, Cantagrel A, Ruyssen-Witrand A (2015) Predictive value of autoantibodies from anti-CCP2, anti-MCV and anti-human citrullinated fibrinogen tests, in early rheumatoid arthritis patients with rapid radiographic progression at 1 year: results from the ESPOIR cohort. RMD Open 1(1):e000180. doi:10.1136/rmdopen-2015-000180

    Article  PubMed  PubMed Central  Google Scholar 

  39. Syversen SW, Goll GL, van der Heijde D, Landewe R, Lie BA, Odegard S, Uhlig T, Gaarder PI, Kvien TK (2010) Prediction of radiographic progression in rheumatoid arthritis and the role of antibodies against mutated citrullinated vimentin: results from a 10-year prospective study. Ann Rheum Dis 69(2):345–351. doi:10.1136/ard.2009.113092

    Article  CAS  PubMed  Google Scholar 

  40. Jilani AA, Mackworth-Young CG (2015) The role of citrullinated protein antibodies in predicting erosive disease in rheumatoid arthritis: a systematic literature review and meta-analysis. Int J Rheumatol 2015:728610. doi:10.1155/2015/728610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Harre U, Georgess D, Bang H, Bozec A, Axmann R, Ossipova E, Jakobsson PJ, Baum W, Nimmerjahn F, Szarka E, Sarmay G, Krumbholz G, Neumann E, Toes R, Scherer HU, Catrina AI, Klareskog L, Jurdic P, Schett G (2012) Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest 122(5):1791–1802. doi:10.1172/JCI60975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kuna AT (2012) Mutated citrullinated vimentin antibodies in rheumatoid arthritis. Clin Chim Acta 413(1–2):66–73. doi:10.1016/j.cca.2011.10.020

    Article  PubMed  Google Scholar 

  43. Reyes-Castillo Z, Palafox-Sánchez CA, Parra-Rojas I, Martínez-Bonilla GE, del Toro-Arreola S, Ramírez-Dueñas MG, Ocampo-Bermudes G, Muñoz-Valle JF (2015) Comparative analysis of autoantibodies targeting peptidylarginine deiminase type 4, mutated citrullinated vimentin and cyclic citrullinated peptides in rheumatoid arthritis: associations with cytokine profiles, clinical and genetic features. Clin Exp Immunol 182(2):119–131. doi:10.1111/cei.12677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gonzalez-Lopez L, Rocha-Muñoz AD, Ponce-Guarneros M, Flores-Chavez A, Salazar-Paramo M, Nava A, Cardona-Muñoz EG, Fajardo-Robledo NS, Zavaleta-Muñiz SA, Garcia-Cobian T, Gamez-Nava JI (2014) Anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti-MCV) relation with extra-articular manifestations in rheumatoid arthritis. J Immunol Res 2014:536050. doi:10.1155/2014/536050

    Article  PubMed  PubMed Central  Google Scholar 

  45. Vassallo R, Luckey D, Behrens M, Madden B, Luthra H, David C, Taneja V (2014) Cellular and humoral immunity in arthritis are profoundly influenced by the interaction between cigarette smoke effects and host HLA-DR and DQ genes. Clin Immunol 152(1–2):25–35. doi:10.1016/j.clim.2014.02.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank Professor Elias Zintzaras, Professor of Biometry and Director of Laboratory of Biomathematics University of Thessaly School of Medicine, Larissa, Greece, for critical review of the article.

Author information

Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Faculty of Medicine, University of Thessaly and University General Hospital of Larissa, Biopolis, 41 110, Larissa, Greece

    Georgia Barouta, Christina G. Katsiari, Ioannis Alexiou, Christos Liaskos, Areti Varna, Dimitrios P. Bogdanos & Lazaros I. Sakkas

  2. Department of Immunology & Histocompatibility, Faculty of Medicine, University of Thessaly and University General Hospital of Larissa, Larissa, Greece

    Anastasios E. Germenis

Authors
  1. Georgia Barouta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christina G. Katsiari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ioannis Alexiou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christos Liaskos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Areti Varna
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dimitrios P. Bogdanos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anastasios E. Germenis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lazaros I. Sakkas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lazaros I. Sakkas.

Ethics declarations

Disclosures

None.

Electronic supplementary material

ESM 1

(DOC 268 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Barouta, G., Katsiari, C.G., Alexiou, I. et al. Anti-MCV antibodies predict radiographic progression in Greek patients with very early (<3 months duration) rheumatoid arthritis. Clin Rheumatol 36, 885–894 (2017). https://doi.org/10.1007/s10067-016-3494-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-016-3494-4

Keywords

Search

Navigation