Anticitrullin antibodies modern markers of rheumatoid arthritis


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Abstract

Modern diagnosis of rheumatoid arthritis (RA) is based on the ARA criteria with seropositivity detection by the rheumatoid factor (RF). In a clinically evident stage of the disease this factor is highly sensitive and specific (about 90%), but in early RA efficacy of this diagnosis is considerably less. RF-IgM phenotype has limitation: frequent detection of this factor in the absence of RA and unstability of RF-IgM phenotype. Therefore, it is necessary to search for new serological criteria of RA diagnosis at early stage of the disease. Proteins containing citrullin appear only in the course of posttranslation modification of arginin residues. This fact gave rise to an original, available for clinical practice method of enzyme immunoassay for detection of antibodies to cyclic citrullinized (ACCP) - filaggrin derivative with synthetic cyclic citrullinized peptide serves as antigenic substance. According to the results of different studies, ACCP specificity in early RA diagnosis is more than 80%, combination of ACCP with ESR, RF-IgM, CRP, morning stiffness - more than 90%. As specificity of combination of these autoantibodies is almost 100%, their simultaneous determination is indicated in patients with undifferentiated arthritis for specification of the diagnosis. ACCP and antibodies to modified citrullinized vimentin (AMCV) significantly correlate with RA activity, are prognostic factors of rapidly progressive course and can be used for the disease prognosis at its early stage. Present-day data on comparative specificity and sensitivity of ACCP and AMCV are not certain and need further study.

About the authors

Natal'ya Petrovna Shilkina

Email: shlkin39@mail.ru

Mariya Sergeevna Luzinova

Email: Knopselgula@rambler.ru

Aleksey Alekseevich Vinogradov

Email: vinograd@fromru.com

N P Shilkina

State Medical Academy, Yaroslavl

State Medical Academy, Yaroslavl

M S Luzinova

State Medical Academy, Yaroslavl

State Medical Academy, Yaroslavl

A A Vinogradov

State Medical Academy, Yaroslavl

State Medical Academy, Yaroslavl

References

  1. Gabriel S. E. The epidemiology of rheumatoid arthritis. Rheum. Dis. Clin. N. Am. 2001; 27: 269-281.
  2. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis. 2002 Update. Arthr. and Rheum. 2002; 46: 328-346.
  3. De Vries-Bouwstra J. K., Goekoop-Ruiterman Y. P. M., van Zeben F. et al. A comparison of clinical and radiological outcomes of four treatment strategies for early rheumatoid arthritis: results of the BEST trial. Ann. Rheum. Dis. 2004; 63: 58.
  4. Grigor C., Capell H., Stirling A. et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single blind randomized controlled trial. Lancet 2004; 364: 263-269.
  5. Smolen J. S., Sokka T., Pincus T., Breedveld F. C. A proposed treatment algorithm for rheumatoid arthritis: aggressive therapy, methotrexate and quantitative measures. Clin. Exp. Rheumatol. 2003; 21 (31): 209-210.
  6. Arnett F. C., Edworthy S., Bloch D. A. et al. The American rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis. Arthr. and Rheum. 1988; 31: 315-324.
  7. Emery P., Breedveld F. C., Dougados M. et al. Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence-based development of a clinical guide. Ann. Rheum. Dis. 2002; 61: 290-297.
  8. Masi A. T., Maldonado-Cocco J. A., Kaplan S. B. et al. Prospective study of the early course of rheumatoid arthritis in young adults: comparison of patients with and without rheumatoid factor positivity at entry and identification of variables correlating with outcome. Semin. Arthr. Rheum. 1976; 4: 299-326.
  9. Voskuyl A. E., Zwinderman A. H., Westedt M. L. et al. Factors associated with the development of vasculitis in rheumatoid arthritis: results of a case-control study. Ann. Rheum. Dis. 1996; 55: 190-192.
  10. Nienhuis R. L., Mandema E. A new serum factor in patients with rheumatoid arthritis, the antiperinuclear factor. Ann. Rheum. Dis. 1964; 23: 302-305.
  11. Young B., Mallya R. K., Leslie R. D. et al. Antikeratin antibodies in rheumatoid arthritis. Br. Med. J. 1979; 2: 97-99.
  12. Schellekens G. A., de Jong B. A., van den Hoogen F. H. et al. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis specific autoantibodies. J. Clin. Invest. 1998; 101: 273-281.
  13. Girbal-Neuhauser E., Durieux J. J., Arnaud M. et al. The epitopes targeted by the rheumatoid arthritis associated antifilaggrin autoantibodies are post-translationally generated on various sites of (pro)filaggrin by deimination of arginine residues. J. Immunol. 1999; 162: 585-594.
  14. Schellekens G. A., Visser H., de Jong B. A. et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthr. and Rheum. 2000; 43: 155- 163.
  15. Лапин С. В., Маслянский А. Л., Мазуров В. И. и др. Сравнительная характеристика специфических аутоантител при ревматоидном артрите. Тер. арх. 2005; 12: 53-59.
  16. Тогизбаев Г., Новиков А. А., Каратеев Д. Е. Прогностическое значение антител к циклическому цитруллинированному пептиду при раннем недифференцированном артрите. В кн.: Сборник материалов Съезда ревматологов России. М.; 2009. 112.
  17. Gao I. K., Haas-Wohrle A., Mueller K. G. et al. Determination of anti-CCP antibodies in patients with suspected rheumatoid arthritis: does it help to predict the diagnosis before referral to a rheumatologist? Ann. Rheum. Dis. 2005; 64: 1516-1517.
  18. Nielen M. M. J., van Schaardenburg D., Reesink H. W. et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arhtr. and Rheum. 2004; 50: 380-386.
  19. Rantapaa-Dahlqvist S., de Jong B. A., Berglin E. et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthr. and Rheum. 2003; 48: 2741-2749.
  20. Van Gaalen F. A., Linn-Rasker S. P., van Venrooij W. J. et al. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthr. and Rheum. 2004; 50: 709-715.
  21. Александрова Е. Н., Чемерис Н. А., Каратеев Д. Е. и др. Антитела к циклическому цитруллинированному пептиду при ревматоидном артрите. Тер. арх. 2004; 12: 64-68.
  22. Каратеев Д. Е., Александрова Е. Н., Демидова Н. В. и др. Антицитруллиновые антитела и данные магнитно-резонансной томографии суставов кисти у больных ранним артритом. Тер. арх. 2008; 10: 72-77.
  23. Vossenaar E. R., Robinson W. H. Citrullination and autoimmune disease: 8-th Bertine Koperberg meeting. Ann. Rheum. Dis. 2005; 64: 1513-1515.
  24. Гусева И. А., Новиков А. А., Каратеев Д. Е. и др. HLA-DR B1*04, антитела к циклическим цитруллинированным пептидам, РФ как факторы риска развития эрозивного процесса у больных ранним ревматоидным артритом через 1 год проспективного наблюдения. В кн.: Сборник материалов Съезда ревматологов России. М.; 2009. 35.
  25. Van Boekel M. A., Vossenaar E. R., van den Hoogen F., van Venrooij W. J. Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthr. Res. 2002; 4: 87-93.
  26. Kastbom A., Strandberg G., Lindroos A., Skogh T. Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project). Ann. Rheum. Dis. 2004; 63: 1085-1089.
  27. Ronnelid J., Wick M. C., Lampa J. et al. Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression. Ann. Rheum. Dis. 2005; 64 (12): 1744-1749.
  28. Alessandri C., Bombardieri M., Papa N. et al. Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following anti-TNFa therapy (infliximab) in rheumatoid arthritis is associated with clinical improvement. Ann. Rheum. Dis. 2004; 63: 1218-1221.
  29. Bobbio-Pallavicini F., Alpini C., Caporali R. et al. Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment. Arthr. Res. Ther. 2004; 6: R264-R272.
  30. Chen H. A., Lin K. C., Chen C. H. et al. The effect of etanercept on anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatoid arthritis. Ann. Rheum. Dis. 2006; 65: 35-39.
  31. De Rycke L., Verhelst X., Kruithof E. et al. Rheumatoid factor, but not anti-citrullinated protein antibodies, is modulated by infliximab treatment in rheumatoid arthritis. Ann. Rheum. Dis. 2005; 64: 299-302.
  32. Forslind K., Ahlmen M., Eberhardt K. et al. BARFOT Study Group. Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Ann. Rheum. Dis. 2004; 63: 1090-1095.
  33. Jansen A. L., van der Horst-Breuinsma I., van Schaardenburg D. et al. Rheumatoid factor and antibodies to cyclic citrullinated peptide differentiate rheumatoid arthritis from undifferentiated polyarthritis in patients with early arthritis. J. Rheumatol. 2002; 29: 2074-2076.
  34. Nielen M. M., van der Horst A. R., van Schaardenburg D. et al. Antibodies to citrullinated human fibrinogen (ACF) have diagnostic and prognostic value in early arthritis. Ann. Rheum. Dis. 2005; 64: 1199-1204.
  35. Nell V. P. K., Machold K. P., Stamm T. A. et al. Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann. Rheum. Dis. 2005; 64: 1731-1736.
  36. Sinclair D., Hull R. G. Why do general practitioners request rheumatoid factor? A study of symptoms, requesting patterns and patient outcome. Ann. Clin. Biochem. 2003; 40: 131-137.
  37. Yamada R., Suzuki A., Chang X., Yamamoto K. Citrullinated proteins in rheumatoid arthritis. Front. Biosci. 2005; 10: 54- 64.
  38. Masson-Bessiere C., Sebbag M., Girbal-Neuhauser E. et al. The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the a- and b-chains of fibrin. J Immunol. 2001; 166: 4177-4184.
  39. Koivula M.-K., Aman S., Karjalainen A. et al. Are there autoantibodies reacting against citrullinated peptides derived from type I and type II collagens in patients with rheumatoid arthritis? Ann. Rheum. Dis. 2005; 64: 1443-1450.
  40. Vossenaar E. R., Despres N., Lapointe E. et al. Rheumatoid arthritis specific anti-SA antibodies target citrullinated vimentin. Arthr. Res. Ther. 2004; 6: R142-R150.
  41. Poulsom H., Charles P. J. Antibodies to citrullinated vimentin are a specific and sensitive marker for the diagnosis of rheumatoid arthritis. Clin. Rev. Allergy Immunol. 2008; 34 (1): 4-10.
  42. Keskin G., Inal A., Keskin D. et al. Diagnostic utility of anti-cyclic citrullinated peptide and anti-modified citrullinated vimentin antibodies in rheumatoid arthritis. Protein Pept. Lett. 2008; 15 (3): 314-317.
  43. Dejaco C., Klotz W., Larcher H. et al. Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis. Arthr. Res. Ther. 2006; 8 (4): R119.
  44. Кузнецова Е. Г., Лушпаева Ю. А., Фадиенко Г. Р. и др. Антитела к циклическому цитруллинированному виментину - основной диагностический маркер ревматоидного артрита. В кн.: Сборник материалов Съезда ревматологов России. М.; 2009.
  45. Багирова Г. Г., Сизова Л. В., Миронова Н. В. Выявление антител к модифицированному цитруллинированному виментину и иммуноглобулину класса М ревматоидного фактора в качестве маркеров раннего ревматоидного артрита. В кн.: Сборник материалов Съезда ревматологов России. М.; 2009. 14.
  46. Bang H., Egerer K., Gauliard A. et al. Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthr. and Rheum. 2007; 56 (8): 2503-2511.
  47. Wagner E., Skoumal M., Bayer P. M., Klaushofer K. Antibody against mutated citrullinated vimentin: a new sensitive marker in the diagnosis of rheumatoid arthritis. Rheumatol. Int. 2009; 29 (11): 1315-1321.
  48. Sghiri R., Bouajina E., Bargaoui D. et al. Value of anti-mutated citrullinated vimentin antibodies in diagnosing rheumatoid arthritis. Rheumatol. Int. 2008; 29 (1): 59-62.
  49. Ursum J., Nielen M. M., van Schaardenburg D. et al. Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study. Arthr. Res. Ther. 2008; 10 (1): R12.
  50. Soös L., Szekanecz Z., Szabö Z. et al. Clinical evaluation of anti-mutated citrullinated vimentin by ELISA in rheumatoid arthritis. J. Rheumatol. 2007; 34 (8): 1658-1663.
  51. Mutlu N., Bicakcigil M, Tasan D. A. et al. Comparative performance analysis of 4 different anti-citrullinated protein assays in the diagnosis of rheumatoid arthritis. J. Rheumatol. 2009; 36 (3): 491-500.
  52. Новиков А. А., Александрова Е. Н., Каратеев Д. Е. и др. Диагностическое значение антител к модифицированному цитруллинированному виментину при раннем ревматоидном артрите. Клин. лаб. диагн. 2008; 8: 27-29.
  53. Салугина С. О., Федоров Е. С., Баранов А. А. Частота определения и диагностическое значение анти-ЦЦП и анти-МЦВ у детей с ранним ювенильным артритом. Науч.-практ. ревматол. 2008; 6: 74-81.
  54. Mathsson L., Mullazehi M., Wick M. C. 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. Arthr. and Rheum. 2008; 58 (1): 36-45.
  55. Innala L., Kokkonen H., Eriksson C. et al. 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. 2008; 35 (6): 1002-1008.
  56. Nicaise R. P., Grootenboer M. S. et al. Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy. Arthr. Res. Ther. 2008; 10 (6): R142.
  57. Новикова Д. С., Попкова Т. В., Александрова Е. Н. Роль антител к циклическому цитруллинированному пептиду и модифицированному цитруллинированному виментину в развитии атеросклеротического поражения сосудов при ревматоидном артрите. В кн.: Сборник материалов Съезда ревматологов России. М.; 2009. 81.

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