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.
Similar content being viewed by others
References
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.
Mahmoud AAIM. Serum protein carbonyl content, total thiol and nitric oxide in patients with rheumatoid arthritis. J Am Sci. 2011;7:683–6.
McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205–19. https://doi.org/10.1056/NEJMra1004965.
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.
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.
Braschi E, Shojania K, Allan GM. Anti-CCP: a truly helpful rheumatoid arthritis test? Can Family Phys. 2016;62(3):234.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
Dalle-Donne I, Giustarini D, Colombo R, Rossi R, Milzani A. Protein carbonylation in human diseases. Trends Mol Med. 2003;9(4):169–76.
García-González A, Gaxiola-Robles R, Zenteno-Savín T. Oxidative stress in patients with rheumatoid arthritis. Rev Invest Clin. 2015;67(1):46–53.
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.
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.
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.
Huether G, Schuff-Werner P. Platelet serotonin acts as a locally releasable antioxidant. Adv Exp Med Biol. 1996;398:299–306.
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.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest:
The authors declare no conflict of interest.
Ethical Approval
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.
Informed consent
Awritten informed consent was obtained from each participating patient.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12291-019-00823-2