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A Study on Association Between Protein Carbonyl and Anti-cyclic Citrullinated Peptide Antibody in Rheumatoid Arthritis: Introducing a New Supplementary Biomarker

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Abstract

Redox state and immune mechanisms are two major factors implicated in rheumatoid arthritis (RA). Regarding some limitations of anti-cyclic citrullinated peptide (anti-CCP) antibody in RA diagnosis, recruiting another strong marker of oxidative stress could lead to more definitive diagnosis. To evaluate the potential of protein carbonyl content as a supplementary biomarker for RA. Eighty patients with RA attending the Research Center from 2015 to 2016 were recruited in this study. Smoker and alcoholic subjects, or those with any other systemic illness were excluded from the study. Demographic information and clinical data were collected. Numbers of swollen and tender joints were determined and RA disease activity was assessed. Serum samples were used for assessing protein carbonyl level, platelet count, and anti-CCP antibody values. Statistical analyses for significant differences were performed according to parametric (Student t test) and nonparametric (Mann–Whitney test) tests. The correlation was determined by Pearson coefficient. There was a significant correlation between protein carbonyl levels and anti-CCP antibodies in active RA (p value = 0.01), but not in remission phase (p value = 0.28). A significant positive correlation was observed between protein carbonyl levels and platelets count in active RA (p value = 0.001), but not in remission phase (p value = 0.85). Protein carbonyl could be considered as a future cost-effective supplementary biomarker, alongside anti-CCP antibody, in active RA diagnosis as it showed a significant positive correlation with anti-CCP antibody and platelet, two major mediators in the disease pathogenesis.

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References

  1. Quinonez-Flores CM, Gonzalez-Chavez SA, Del Rio Najera D, Pacheco-Tena C. Oxidative stress relevance in the pathogenesis of the rheumatoid arthritis: a systematic review. Biomed Res Int. 2016;2016:6097417. https://doi.org/10.1155/2016/6097417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mahmoud AAIM. Serum protein carbonyl content, total thiol and nitric oxide in patients with rheumatoid arthritis. J Am Sci. 2011;7:683–6.

    Google Scholar 

  3. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205–19. https://doi.org/10.1056/NEJMra1004965.

    Article  CAS  Google Scholar 

  4. Klareskog L, Lundberg K, Malmstrom V. Autoimmunity in rheumatoid arthritis: citrulline immunity and beyond. Adv Immunol. 2013;118:129–58. https://doi.org/10.1016/B978-0-12-407708-9.00003-0.

    Article  CAS  PubMed  Google Scholar 

  5. Porto LS, Tavares WCJ, Costa DA, Lanna CC, Kakehasi AM. Anti-CCP antibodies are not a marker of severity in established rheumatoid arthritis: a magnetic resonance imaging study. Rev Bras Reumatol Engl Ed. 2017;57(1):15–22. https://doi.org/10.1016/j.rbre.2015.07.018.

    Article  PubMed  Google Scholar 

  6. Braschi E, Shojania K, Allan GM. Anti-CCP: a truly helpful rheumatoid arthritis test? Can Family Phys. 2016;62(3):234.

    Google Scholar 

  7. Bizzaro N, Mazzanti G, Tonutti E, Villalta D, Tozzoli R. Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis. Clin Chem. 2001;47(6):1089–93.

    Article  CAS  Google Scholar 

  8. Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci IJBS. 2008;4(2):89–96.

    CAS  PubMed  Google Scholar 

  9. Seven A, Guzel S, Aslan M, Hamuryudan V. Lipid, protein, DNA oxidation and antioxidant status in rheumatoid arthritis. Clin Biochem. 2008;41(7–8):538–43. https://doi.org/10.1016/j.clinbiochem.2008.01.029.

    Article  CAS  PubMed  Google Scholar 

  10. Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta. 2003;329(1):23–38.

    Article  CAS  Google Scholar 

  11. Datta S, Kundu S, Ghosh P, De S, Ghosh A, Chatterjee M. Correlation of oxidant status with oxidative tissue damage in patients with rheumatoid arthritis. Clin Rheumatol. 2014;33(11):1557–64. https://doi.org/10.1007/s10067-014-2597-z.

    Article  PubMed  Google Scholar 

  12. Boilard E, Blanco P, Nigrovic PA. Platelets: active players in the pathogenesis of arthritis and SLE. Nat Rev Rheumatol. 2012;8(9):534–42. https://doi.org/10.1038/nrrheum.2012.118.

    Article  CAS  PubMed  Google Scholar 

  13. Habets KL, Trouw LA, Levarht EW, Korporaal SJ, Habets PA, de Groot P, et al. Anti-citrullinated protein antibodies contribute to platelet activation in rheumatoid arthritis. Arthritis Res Ther. 2015;17:209. https://doi.org/10.1186/s13075-015-0665-7.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Arnett FC, Edworthy SM, Bloch DA, Mcshane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheumatol. 1988;31(3):315–24.

    Article  CAS  Google Scholar 

  15. Prevoo M, Van’T Hof MA, Kuper H, Van Leeuwen M, Van De Putte L, Van Riel P. Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheumatol. 1995;38(1):44–8.

    Article  CAS  Google Scholar 

  16. Pattison DJ, Winyard PG. Dietary antioxidants in inflammatory arthritis: do they have any role in etiology or therapy? Nat Clin Pract Rheumatol. 2008;4(11):590–6. https://doi.org/10.1038/ncprheum0920.

    Article  CAS  PubMed  Google Scholar 

  17. Mitchell DM, Spitz PW, Young DY, Bloch DA, McShane DJ, Fries JF. Survival, prognosis, and causes of death in rheumatoid arthritis. Arthritis Rheum. 1986;29(6):706–14.

    Article  CAS  Google Scholar 

  18. Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, et al. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994;37(4):481–94.

    Article  CAS  Google Scholar 

  19. Littlejohn EA, Monrad SU. Early diagnosis and treatment of rheumatoid arthritis. Prim Care. 2018;45(2):237–55. https://doi.org/10.1016/j.pop.2018.02.010.

    Article  PubMed  Google Scholar 

  20. Finckh A, Liang MH, van Herckenrode CM, de Pablo P. Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: a meta-analysis. Arthritis Rheum. 2006;55(6):864–72. https://doi.org/10.1002/art.22353.

    Article  PubMed  Google Scholar 

  21. Niewold TB, Harrison MJ, Paget SA. Anti-CCP antibody testing as a diagnostic and prognostic tool in rheumatoid arthritis. QJM Mon J Assoc Phys. 2007;100(4):193–201. https://doi.org/10.1093/qjmed/hcm015.

    Article  CAS  Google Scholar 

  22. Park M, Pyun JC, Akter H, Nguyen BT, Kang MJ. Evaluation of a specific diagnostic marker for rheumatoid arthritis based on cyclic citrullinated peptide. J Pharm Biomed Anal. 2015;115:107–13. https://doi.org/10.1016/j.jpba.2015.06.032.

    Article  CAS  PubMed  Google Scholar 

  23. Porto LS, Tavares Junior WC, Costa DA, Lanna CC, Kakehasi AM. Anti-CCP antibodies are not a marker of severity in established rheumatoid arthritis: a magnetic resonance imaging study. Revista brasileira de reumatologia. 2015. https://doi.org/10.1016/j.rbr.2015.07.009.

    Article  PubMed  Google Scholar 

  24. Pincus T, Sokka T. Laboratory tests to assess patients with rheumatoid arthritis: advantages and limitations. Rheum Dis Clin N Am. 2009;35(4):731–4. https://doi.org/10.1016/j.rdc.2009.10.007.

    Article  Google Scholar 

  25. Mirshafiey A, Mohsenzadegan M. The role of reactive oxygen species in immunopathogenesis of rheumatoid arthritis. Iran J Allergy Asthma Immunol. 2008;7(4):195–202. https://doi.org/07.04/ijaai.195202

  26. Dalle-Donne I, Giustarini D, Colombo R, Rossi R, Milzani A. Protein carbonylation in human diseases. Trends Mol Med. 2003;9(4):169–76.

    Article  CAS  Google Scholar 

  27. García-González A, Gaxiola-Robles R, Zenteno-Savín T. Oxidative stress in patients with rheumatoid arthritis. Rev Invest Clin. 2015;67(1):46–53.

    PubMed  Google Scholar 

  28. Stamp LK, Khalilova I, Tarr JM, Senthilmohan R, Turner R, Haigh RC, et al. Myeloperoxidase and oxidative stress in rheumatoid arthritis. Rheumatology (Oxford). 2012;51(10):1796–803. https://doi.org/10.1093/rheumatology/kes193.

    Article  CAS  Google Scholar 

  29. Dalle-Donne I, Rossi R, Colombo R, Giustarini D, Milzani A. Biomarkers of oxidative damage in human disease. Clin Chem. 2006;52(4):601–23. https://doi.org/10.1373/clinchem.2005.061408.

    Article  CAS  PubMed  Google Scholar 

  30. Harifi G, Sibilia J. Pathogenic role of platelets in rheumatoid arthritis and systemic autoimmune diseases. Perspectives and therapeutic aspects. Saudi Med J. 2016;37(4):354–60. https://doi.org/10.15537/smj.2016.4.14768.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Huether G, Schuff-Werner P. Platelet serotonin acts as a locally releasable antioxidant. Adv Exp Med Biol. 1996;398:299–306.

    Article  CAS  Google Scholar 

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Acknowledgements

We are very grateful to all patients who participated in this study. This project was funded by the Research Council of Mashhad University of Medical Sciences (grant number 910276) providing financial support for the conduct of the research.

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Correspondence to Seyed Isaac Hashemy.

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All procedures performed in the current study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.

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Khorasani, S., Boroumand, N., Ghaeni Pasavei, A. et al. A Study on Association Between Protein Carbonyl and Anti-cyclic Citrullinated Peptide Antibody in Rheumatoid Arthritis: Introducing a New Supplementary Biomarker. Ind J Clin Biochem 35, 347–352 (2020). https://doi.org/10.1007/s12291-019-00823-2

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  • DOI: https://doi.org/10.1007/s12291-019-00823-2

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