Diagnostic effectiveness of anti-citrullinated peptides antibodies of second and third generations for rheumatoid arthritis

Authors

  • Goitybell Martínez Téllez Universidad de Ciencias Médicas de La Habana. Centro Nacional de Genética Médica. La Habana.
  • Bárbara Torres Rives Universidad de Ciencias Médicas de La Habana. Centro Nacional de Genética Médica. La Habana.
  • Jorge Alexis Gómez Universidad de Ciencias Médicas de La Habana. Centro de Reumatología. La Habana.
  • Dinorah Prada Hernández Centro Nacional de Reumatología.
  • Vicky Sánchez Rodríguez Centro Nacional de Genética Médica. La Habana.

Abstract

Introduction: Rheumatoid arthritis is an autoimmune disease characterized by the presence of antibodies against citrullinated peptides, which are one of the indicators for the diagnosis of a disease.  The usefulness of different methods for the determination of these antibodies in the diagnosis of Cuban patients with rheumatoid arthritis is necessary to be established.

Objective: To establish the diagnostic effectiveness of the second (anti-CCP2) and third (anti-CCP3) generation assays for the determination these antibodies against citrullinated peptides in Cuban patients with rheumatoid arthritis.

Material and method: 101 patients with rheumatoid arthritis, 58 patients with other rheumatic and inflammatory diseases, and 43 healthy persons participated in the study. The diagnostic efficiency of rheumatoid factor (RF), anti-CCP2 and anti-CCP3 antibodies were determined using ELISA test, by calculating sensitivity, specificity, and positive and negative predictive values.

Results: The anti-CCP2 assay showed a better balance of sensitivity (48.5 %) and specificity (98.0 %).  The lower sensibility was observed for RF (40.3%) when the specificity was set at 98 %. Specificity increased to 100% when anti-CCP2 and RF assays were used. All autoantibodies showed association with C-reactive protein and correlation with erythrocyte sedimentation rate. Only anti-CCP2 antibodies showed no correlation with the DAS28 clinical indicator.

Conclusions: Anti-CCP2 antibodies are the ones of greater effectiveness in the diagnosis of Cuban patients with rheumatoid arthritis. RF identification allows to identify seronegative anti-CCP2 patients; therefore, the combination of both immunoassays leads to an improvement in the diagnostic effectiveness.  

Keywords: Rheumatoid arthritis, cyclic citrullinated peptide, antibodies, anti-CCP2, anti-CCP3, diagnosis.

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Author Biographies

Goitybell Martínez Téllez, Universidad de Ciencias Médicas de La Habana. Centro Nacional de Genética Médica. La Habana.

Master en Química Farmacéutica. Investigador Auxiliar.

Bárbara Torres Rives, Universidad de Ciencias Médicas de La Habana. Centro Nacional de Genética Médica. La Habana.

Especialista en Inmunología. Profesor e Investigador auxiliar.

Dinorah Prada Hernández, Centro Nacional de Reumatología.

Especialista en Reumatología.

References

1. Abbas AK, Lichtman A, Pillai S. Inmunología celular y molecular. 8va ed. Barcelona: Elseiver Saunders; 2015.

2. Arnett FC, Bloch DA. The American Rheumatism association 1987. Revised criteria for the classification of Rheumatoid Arthritis.Arthritis Rheum. 1988; 31:315-23.

3. Arana V, Ku R, Canul J, Chan Zapata I, Torres J. Importancia clínica de los anticuerpos péptidos cíclicos citrulinados en el diagnóstico de la artritis reumatoide. Revista Iberoamericana de Ciencias 2015;2(2):119-132.

4. Cornillet M, Sebbag M, Verrouil E, Magyar A, Babos F, Ruyssen-Witrand A y col. The fibrin-derived citrullinated peptide ß60-74Cit60,72,74 bears the major ACPA epitope recognised by the rheumatoid arthritis-specific anticitrullinated fibrinogen autoantibodies and anti-CCP2 antibodies. Ann Rheum Dis. 2014. 73(6):1246-52

5. 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 (Oxford). 2011; 50:830–7.

6. Gavrila BI, Ciofu C, Stoica V. Biomarkers in Rheumatoid Arthritis, what is new? J Med Life. 2016;9(2):144-148.

7. Díaz-Toscano ML, Olivas-Flores EM, Zavaleta-uñiz SA, Gamez-Nava JI, Cardona-Muñoz EG, Ponce-Guarneros M y col. 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 anticitrullinated cyclic peptides testing. Biomed Res Intl. [Internet]. 2014;2014:198198 [aprox. 6 p.]. Disponible en: http://dx.doi.org/ 10.1155/2014/198198.

8. Demoruelle M, ParishM, Derber L, Kolfenbach J, Hughes-Austin J, Weisman M y col. Anti-cyclic citrullinated peptide assays differ in subjects at elevated risk for rheumatoid arthritis and subjects with established disease. Arthritis Rheum. 2013; 65(9):2243–2252.

9. Szekanecz Z, Szab´o Z, Zeher M Soós L, Dankó K, Horváth I y col. Superior performance of the CCP3.1 test compared to CCP2 and MCV in the rheumatoid factor-negative RA population. Immunologic Research. 2013;56(2-3):439-43.

10. Soroush M, Mahoudi M, Akhlagh M. Determination of specificity and sensitivity of rheumatoid factor and anti CCP tests in patients with RA in private clinic in Tehran, Iran Biomed & Pharmacol J. 2016;9(2):775-80.

11. Koga T, Okada A, Fukuda T, Hidaka T, Ishii T, Ueki Y y col. Anti-citrullinated peptide antibodies are the strongest predictor of clinically relevant radiographic progression in rheumatoid arthritis patients achieving remission or low disease activity: A post hoc analysis of a nationwide cohort in Japan. PLoS ONE [Internet]. 2017; 12(5): [aprox. 24 p.]. Disponible en: https://doi.org/10.1371/journal.pone.0175281

12. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO y col. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569-2581.

13. Mathsson L, Fountain DL, Cadwell KK, Madrigal AM, Gallo G y Poorafshar M. The performance of anti-cyclic citrullinated peptide assays in diagnosing rheumatoid arthritis: a systematic review and meta-analysis. Clinical and Experimental Rheumatology. 2018;36:144-152.

14. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. [Internet]. 2013; 310(20): [aprox. 7 p.]. Disponible en: http://www.wma.net/en/30publications/10policies/ b3/index.html.

15. Henrique da Mota LM, Neto LL, Pereira IA, Burlingame R, Menard H, Laurindo IM. Autoantibodies in early rheumatoid arthritis – Brasília cohort – results of a three-year serial analysis. Rev Bras Reumatol. 2011; 51(6):558-571.

16. Haye MJ, Retamozo S, Vetorazzi L, Peano N, Díaz PE, Castaños MS y col. Anticuerpo anticitrulina y manifestaciones extra articulares en artritis reumatoidea. Medicina (buenos aires). [Internet]. 2013; 73(1): [aprox. 5 p.]. Disponible en: www.scielo.org.ar/scielo.php?script=sci_arttext&pid... 76802013000100004

17. Gonzalez-Lopez L, Rocha-Muñoz AD, Ponce-Guarneros M, Flores-Chavez A, Salazar-Paramo M, Nava A y col. Anti-cyclic citrullinated peptide (Anti-CCP) and anti-mutated citrullinated vimentin (Anti-MCV). Relation with extra-articular manifestations in rheumatoid arthritis. J Immunol Res. [Internet]. 2014; 72(1): [aprox. 10 p.]. Disponible en: http://dx.doi.org/10.1155/2014/536050

18. Kokuina H, Chico A, Carballar L, Gutiérrez A, Soto J, Estévez M y col. Factor reumoideo: Asociación con la erosión radiológica y con la actividad de la artritis reumatoidea. Rev Cubana Med 2008; 47(3). [aprox. 14 p.]. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1729-519X2015000400003.

19. González M, Rueda J, González H, Salcedo M. Diagnostic utility of antibody to cyclic citrullinated peptide as a diagnostic test for rheumatoid arthritis patients. Rev Colomb Reumatol 2013;20(1): 9-18.

20. González M, Rueda J, González H, Cantora E. Artritis reumatoide temprana: resultados clínicos y funcionales de una cohorte en un centro de alta complejidad, Cali-Colombia. Rev Colomb Reumatol 2016;23(3):148-154.

21. Wagner C, Sokolove J, Lahey L, Bengtsson C, Saevarsdottir S, Alfredsson L y col. Identification of anticitrullinated protein antibody reactivity in a subset of anti-CCP-negative rheumatoid arthritis: association with cigarette smoking and HLA-DRB1 ‘shared epitope’ alleles. Ann Rheum Dis 2015;74:589-586.

Published

2018-08-14

How to Cite

1.
Martínez Téllez G, Torres Rives B, Gómez JA, Prada Hernández D, Sánchez Rodríguez V. Diagnostic effectiveness of anti-citrullinated peptides antibodies of second and third generations for rheumatoid arthritis. Rev haban cienc méd [Internet]. 2018 Aug. 14 [cited 2025 Jul. 1];17(4):540-54. Available from: https://revhabanera.sld.cu/index.php/rhab/article/view/2192

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Section

Clinical and pathological sciences