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Unique Correlation Between Mutated Citrullinated Vimentine IgG Autoantibodies and Markers of Systemic Inflammation in Rheumatoid Arthritis Patients

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Abstract

Rheumatoid arthritis (RA) is the most common inflammatory systemic autoimmune disease, primarily affecting the peripheral joints. Anti-mutated citrullinated vimentin autoantibodies (anti-MCV) of IgG isotype were shown to be a useful diagnostic marker of RA especially in RA patients who were anti-cyclic citrullinated protein autoantibodies (anti-CCP) negative. Nevertheless, published data correlates rheumatoid factor (RF), anti-CCP or anti-MCV antibodies with either erythrocyte sedimentation rate (ESR) or serum C-reactive protein (CRP) as markers of disease activity, not investigated the possible correlations of RA autoantibodies towards ESR and CRP in comparison. Herein, we aim to evaluate the usefulness of anti-MCV as a dependable marker in established RA compared with anti-CCP and RF antibodies and to examine correlations between RF, anti-CCP and anti-MCV antibodies towards ESR and serum CRP. Serum RF-IgA, RF-IgM, anti-CCP and anti-MCV levels were measured in 30 patients with RA and 40 patients with other autoimmune diseases (non-RA) compared with 20 normal subjects. Specificity, sensitivity and AUC for RF antibodies, anti-CCP and anti-MCV were calculated towards RA diagnosis. Our results showed that ESR and CRP had significantly higher values in both RA and non-RA patients compared with our healthy controls with observed significant increment in RA patients compared with non-RA patients. An important finding from our study is that 33.3 % of RA patients were anti-CCP negative but being positive towards anti-MCV. Also, in-between 36.7 up to 40 % of RA patients were RF-IgA and RF-IgM negative while being anti-MCV positive. Anti-MCV antibodies showed the highest specificity and sensitivity (97.5 and 86.6 %, respectively) towards RA diagnosis with the highest AUC value (0.920) compared with anti-CCP and RF antibodies. Correlation analyses revealed that there was no significant correlation between ESR along with CRP towards RF-IgA, RF-IgM and anti-CCP while profound highly significant correlation exhibited between ESR and CRP towards anti-MCV data (r = 0.879 and 0.994, respectively). Thus, our data suggest that the assessment of serum anti-MCV autoantibodies along with ESR and CRP considered as a simple laboratory regime for monitoring RA patients to assess and follow-up disease activity. The addition of anti-MCV autoantibodies to serologic markers in the ACR/EULAR classification criteria for RA will add points for patients with negative anti-CCP and RF antibodies.

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References

  1. Lutteri L, Malaise M, Chapelle JP. Comparison of second- and third-generation anti-cyclic citrullinated peptide antibodies assays for detecting rheumatoid arthritis. Clin Chim Acta. 2007;386:76–81.

    Article  PubMed  CAS  Google Scholar 

  2. Kuna AT. Mutated citrullinated vimentin antibodies in rheumatoid arthritis. Clin Chim Acta. 2012;413:66–73.

    Article  PubMed  Google Scholar 

  3. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, et al. Rheumatoid arthritis classification criteria: an american college of rheumatology/european league against rheumatism collaborative initiative. Ann Rheum Dis. 2010;62:1580–8.

    Article  Google Scholar 

  4. Sizova L. Diagnostic value of antibodies to modified citrullinated vimentin in early rheumatoid arthritis. Hum Immunol. 2012;73:389–92.

    Article  PubMed  CAS  Google Scholar 

  5. Wener MH. Laboratory tests for autoimmune rheumatologic disorders. Educational review manual in rheumatology. 4th ed. New York: Castle Connolly Graduate Medical Publishing Ltd; 2007. p. 1–42.

    Google Scholar 

  6. Castro C, Gourley M. Diagnostic testing and interpretation of tests for autoimmunity. J Allergy Clin Immunol. 2010;125(2):S238–47.

    Article  PubMed  Google Scholar 

  7. Colglazier CL, Sutej PG. Laboratory testing in the rheumatic diseases: a practical review. South Med J. 2005;98:185–91.

    Article  PubMed  Google Scholar 

  8. Taylor P, Gartemann J, Hsieh J, Creeden J. A systematic review of serum biomarkers anti-cyclic citrullinated peptide and rheumatoid factor as tests for rheumatoid arthritis. Autoimmun Dis. 2011; Article ID 815038.

  9. Schellekens GA, de Jong BAW, van den Hoogen FHJ, van de Putte LBA, van Venrooij WJ. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest. 1998;101:273–81.

    Article  PubMed  CAS  Google Scholar 

  10. Szodoray P, Szabó Z, Kapitány A, Gyetvai A, Lakos G, Szántó S, Szücs G, Szekanecz Z. Anti-citrullinated protein/peptide autoantibodies in association with genetic and environmental factors as indicators of disease outcome in rheumatoid arthritis. Autoimmun Rev. 2010;9:140–3.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  12. Bang H, Egerer K, Gauliard A, Luthke K, Rudolph PE, Fredenhagen G, et al. Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum. 2007;56:2503–11.

    Article  PubMed  CAS  Google Scholar 

  13. Luime JJ, Colin EM, Hazes JM, Lubberts E. 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. 2010;69:337–44.

    Article  PubMed  CAS  Google Scholar 

  14. Vossenaar ER, Despres N, Lapointe E, Van Der Heijden A, Lora M, Senshu T, et al. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthritis Res Ther. 2004;6:142–50.

    Article  Google Scholar 

  15. Nicaise Roland P, Grootenboer Mignot S, Bruns A, Hurtado M, Palazzo E, Hayem G, et al. Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy. Arthritis Res Ther. 2008;10:R142.

    Article  PubMed  Google Scholar 

  16. Wiik AS, van Venrooij WJ, van Beers J, Pruijn G. All you wanted to know about anti-CCP but were afraid to ask. Autoimmun Rev. 2010;10:90–3.

    Article  PubMed  CAS  Google Scholar 

  17. Syversen SW, Goll GL, van der Heijde D, Landewé R, Lie BA, Odegård S, et al. 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. 2010;69(2):345–51.

    Article  PubMed  CAS  Google Scholar 

  18. Ursum J, Nielen MM, van Schaardenburg D, van der Horst AR, van de Stadt RJ, Dijkmans BA, et al. Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study. Arthritis Res Ther. 2008;10:R12.

    Article  PubMed  Google Scholar 

  19. Sahin O, Kaptanoglu E, Bakici MZ, Sezer H, Elden H, Hizmetli S. Dianostic value of autoantibodies against citrullinated peptide antigens in rheumatoid arthritis: comparison of different commercial kits. Turk J Rheum. 2011;26:13–8.

    Article  Google Scholar 

  20. Mathsson L, Mullazehi M, Wick MC, Sjöberg O, van Vollenhoven R, Klareskog L, et al. 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. 2008;58(1):36–45.

    Article  PubMed  CAS  Google Scholar 

  21. Keskin G, Inal A, Keskin D, Pekel A, Baysal O, Dizer U, et al. Diagnostic utility of anti-cyclic citrullinated peptide and anti-modified citrullinated vimentin antibodies in rheumatoid arthritis. Protein Pept Lett. 2008;15(3):314–7.

    Article  PubMed  CAS  Google Scholar 

  22. van Steendam K, Tilleman K, Deforce D. The relevance of citrullinated vimentin in the production of antibodies against citrullinated proteins and the pathogenesis of rheumatoid arthritis. Rheumatology. 2011;50:830–70.

    Article  PubMed  Google Scholar 

  23. Damjanovska L, Thabet MM, Levarth EW, Stoeken-Rijsbergen G, van der Voort EI, Toes RE, et al. Diagnostic value of anti-MCV antibodies in differentiating early inflammatory arthritis. Ann Rheum Dis. 2010;69:730–2.

    Article  PubMed  CAS  Google Scholar 

  24. Raza K, Mathsson L, Buckley CD, Filer A, Ronnelid J. Anti-modified citrullinated vimentin (MCV) antibodies in patients with very early synovitis. Ann Rheum Dis. 2010;69:627–8.

    Article  PubMed  CAS  Google Scholar 

  25. Wagner E, Skoumal M, Bayer PM, Klaushofer K. Antibody against mutated citrullinated vimentin: a new sensitive marker in the diagnosis of rheumatoid arthritis. Rheum Int. 2009;29:1315–21.

    Article  CAS  Google Scholar 

  26. Wolfe F. Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate in patients with rheumatoid arthritis. J Rheum. 1997;24:1477–85.

    PubMed  CAS  Google Scholar 

  27. Lindqvist E, Eberhardt K, Bendtzen K, Heinegard D, Saxne T. Prognostic laboratory markers of joint damage in rheumatoid arthritis. Ann Rheum Dis. 2005;64:196–201.

    Article  PubMed  CAS  Google Scholar 

  28. Greiner A, Plischke H, Kellner H, Gruber R. Association of anticyclic citrullinated peptide antibodies, anti-citrullin antibodies, and IgM and IgA rheumatoid factors with serological parameters of disease activity in rheumatoid arthritis. Ann N Y Acad Sci. 2005;1050:295–303.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt

    Walid E. Zahran, Magda I. Mahmoud & Kamal A. Shalaby

  2. Rheumatology Unit, Ain Shams University Hospital, Cairo, Egypt

    Manal H. Abbas

Authors
  1. Walid E. Zahran
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  2. Magda I. Mahmoud
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  3. Kamal A. Shalaby
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  4. Manal H. Abbas
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Correspondence to Walid E. Zahran.

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Zahran, W.E., Mahmoud, M.I., Shalaby, K.A. et al. Unique Correlation Between Mutated Citrullinated Vimentine IgG Autoantibodies and Markers of Systemic Inflammation in Rheumatoid Arthritis Patients. Ind J Clin Biochem 28, 272–276 (2013). https://doi.org/10.1007/s12291-012-0272-1

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