Does Eta Protein Differentiate Rheumatoid Arthritis from Psoriatic Arthritis?

  • Authors: Kor A.1, Orhan K.2, Maraş Y.3, Oğuz E.4, Unan M.5, Dilek G.6, Erten Ş.7, Nas K.8
  • Affiliations:
    1. Department of Rheumatology, Aksaray Training and Research Hospital
    2. Department of Rheumatology, Ankara Bilkent City Hospital
    3. Department of Rheumatology, University of Health Sciences, Ankara City Hospital
    4. Department of Medical Biochemistry, Ankara Bilkent City Hospital
    5. Department of Physical Medicine and Rehabilitation Division of Rheumatology, Faculty of Medicine,, Sakarya University
    6. Department of Rheumatology, Faculty of Medicine, Bolu Izzet Baysal University
    7. Department of Rheumatology, Ankara Bilkent City Hospita, Ankara Bilkent City Hospital, Ankara Yıldırım Beyazıt University
    8. Department of Physical Medicine and Rehabilitation Division of Rheumatology and Immunology, Faculty of Medicine, Sakarya University
  • Issue: Vol 31, No 39 (2024)
  • Pages: 6510-6520
  • Section: Anti-Infectives and Infectious Diseases
  • URL: https://hum-ecol.ru/0929-8673/article/view/645114
  • DOI: https://doi.org/10.2174/0109298673295359240422115759
  • ID: 645114

Cite item

Full Text

Abstract

Aim:The clinical symptoms and laboratory markers of Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA) can be very similar, so making a differential diagnosis between these two diseases is often difficult. Serological parameters to be used in differential diagnosis can guide the clinician. This study aimed to investigate the usability of 14-3-3η (eta) protein as a biomarker in the differential diagnosis of PsA and RA, and the relationships between eta protein and disease activity scores and joint erosions in PsA and RA.

Methods:54 PsA patients, 53 RA patients, and 56 healthy individuals were included in this study. The ELISA (Enzyme-Linked ImunoSorbent Assay) kit was used as a quantitative sandwich enzyme immunoassay technique to detect human eta protein levels. Receiver- operating Characteristic (ROC) curves analysis was used to determine the sensitivity and specificity of the eta protein.

Results:Eta protein levels were found to be significantly higher in the RA group than in the PsA [B: -0.341, OR (95% CI): 0.711 (0.556-0.909), p: 0.007] and control [B: -0.225, OR (95% CI): 0.798 (0.641-0.995), p: 0.045] groups. Eta protein median values were significantly higher in patients with joint erosion than in those without [β= 0.151, OR (95% CI): 1.163 (1.003-1.349), p: 0.046].

Conclusion:Eta protein levels are higher in the serum of RA patients than PsA and are associated with joint erosion. Eta protein may be a potential biomarker in the differential diagnosis of RA and PsA. It may represent a possible therapeutic step in the pathophysiological pathways in the development of joint erosion.

About the authors

Ahmet Kor

Department of Rheumatology, Aksaray Training and Research Hospital

Author for correspondence.
Email: info@benthamscience.net

Kevser Orhan

Department of Rheumatology, Ankara Bilkent City Hospital

Email: info@benthamscience.net

Yüksel Maraş

Department of Rheumatology, University of Health Sciences, Ankara City Hospital

Email: info@benthamscience.net

Esra Oğuz

Department of Medical Biochemistry, Ankara Bilkent City Hospital

Email: info@benthamscience.net

Mehtap Unan

Department of Physical Medicine and Rehabilitation Division of Rheumatology, Faculty of Medicine,, Sakarya University

Email: info@benthamscience.net

Gamze Dilek

Department of Rheumatology, Faculty of Medicine, Bolu Izzet Baysal University

Email: info@benthamscience.net

Şükran Erten

Department of Rheumatology, Ankara Bilkent City Hospita, Ankara Bilkent City Hospital, Ankara Yıldırım Beyazıt University

Email: info@benthamscience.net

Kemal Nas

Department of Physical Medicine and Rehabilitation Division of Rheumatology and Immunology, Faculty of Medicine, Sakarya University

Email: info@benthamscience.net

References

  1. Ritchlin, C.T.; Colbert, R.A.; Gladman, D.D. Psoriatic Arthritis. N. Engl. J. Med., 2017, 376(10), 957-970. doi: 10.1056/NEJMra1505557 PMID: 28273019
  2. Smolen, J.S.; Landewé, R.; Bijlsma, J.; Burmester, G.; Chatzidionysiou, K.; Dougados, M.; Nam, J.; Ramiro, S.; Voshaar, M.; van Vollenhoven, R.; Aletaha, D.; Aringer, M.; Boers, M.; Buckley, C.D.; Buttgereit, F.; Bykerk, V.; Cardiel, M.; Combe, B.; Cutolo, M.; van Eijk-Hustings, Y.; Emery, P.; Finckh, A.; Gabay, C.; Gomez-Reino, J.; Gossec, L.; Gottenberg, J.E.; Hazes, J.M.W.; Huizinga, T.; Jani, M.; Karateev, D.; Kouloumas, M.; Kvien, T.; Li, Z.; Mariette, X.; McInnes, I.; Mysler, E.; Nash, P.; Pavelka, K.; Poór, G.; Richez, C.; van Riel, P.; Rubbert-Roth, A.; Saag, K.; da Silva, J.; Stamm, T.; Takeuchi, T.; Westhovens, R.; de Wit, M.; van der Heijde, D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann. Rheum. Dis., 2017, 76(6), 960-977. doi: 10.1136/annrheumdis-2016-210715 PMID: 28264816
  3. Knani, I.; Bouzidi, H.; Zrour, S.; Bergaoui, N.; Hammami, M.; Kerkeni, M. Increased serum concentrations of N ɛ -carboxymethyllysine are related to the presence and the severity of rheumatoid arthritis. Ann. Clin. Biochem., 2018, 55(4), 430-436. doi: 10.1177/0004563217733500 PMID: 28882063
  4. Van Hoovels, L.; Vander Cruyssen, B.; Sieghart, D.; Bonroy, C.; Nagy, E.; Pullerits, R.; Čučnik, S.; Dahle, C.; Heijnen, I.; Bernasconi, L.; Benkhadra, F.; Bogaert, L.; Van Den Bremt, S.; Van Liedekerke, A.; Vanheule, G.; Robbrecht, J.; Studholme, L.; Wirth, C.; Müller, R.; Kyburz, D.; Sjöwall, C.; Kastbom, A.; Ješe, R.; Jovancevic, B.; Kiss, E.; Jacques, P.; Aletaha, D.; Steiner, G.; Verschueren, P.; Bossuyt, X. IgA rheumatoid factor in rheumatoid arthritis. Clin. Chem. Lab. Med., 2022, 60(10), 1617-1626. doi: 10.1515/cclm-2022-0244 PMID: 35790193
  5. Smolen, J.S. Rheumatoid arthritis Primer behind the scenes. Nat. Rev. Dis. Primers, 2020, 6(1), 32. doi: 10.1038/s41572-020-0168-y PMID: 32327647
  6. Smolen, J.S.; Landewé, R.B.M.; Bijlsma, J.W.J.; Burmester, G.R.; Dougados, M.; Kerschbaumer, A.; McInnes, I.B.; Sepriano, A.; van Vollenhoven, R.F.; de Wit, M.; Aletaha, D.; Aringer, M.; Askling, J.; Balsa, A.; Boers, M.; den Broeder, A.A.; Buch, M.H.; Buttgereit, F.; Caporali, R.; Cardiel, M.H.; De Cock, D.; Codreanu, C.; Cutolo, M.; Edwards, C.J.; van Eijk-Hustings, Y.; Emery, P.; Finckh, A.; Gossec, L.; Gottenberg, J.E.; Hetland, M.L.; Huizinga, T.W.J.; Koloumas, M.; Li, Z.; Mariette, X.; Müller-Ladner, U.; Mysler, E.F.; da Silva, J.A.P.; Poór, G.; Pope, J.E.; Rubbert-Roth, A.; Ruyssen-Witrand, A.; Saag, K.G.; Strangfeld, A.; Takeuchi, T.; Voshaar, M.; Westhovens, R.; van der Heijde, D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann. Rheum. Dis., 2020, 79(6), 685-699. doi: 10.1136/annrheumdis-2019-216655 PMID: 31969328
  7. Popescu, C.; Zofotă, S.; Bojincă, V.; Ionescu, R. Anti- cyclic citrullinated peptide antibodies in psoriatic arthritis--cross-sectional study and literature review. J. Med. Life, 2013, 6(4), 376-382. PMID: 24701255
  8. Bizzaro, N. Antibodies to citrullinated peptides: a significant step forward in the early diagnosis of rheumatoid arthritis. Clin. Chem. Lab. Med., 2007, 45(2), 150-157. doi: 10.1515/CCLM.2007.027 PMID: 17311500
  9. Burmester, G.R.; Pope, J.E. Novel treatment strategies in rheumatoid arthritis. Lancet, 2017, 389(10086), 2338-2348. doi: 10.1016/S0140-6736(17)31491-5 PMID: 28612748
  10. Gossec, L.; Smolen, J.S.; Ramiro, S.; de Wit, M.; Cutolo, M.; Dougados, M.; Emery, P.; Landewé, R.; Oliver, S.; Aletaha, D.; Betteridge, N.; Braun, J.; Burmester, G.; Cañete, J.D.; Damjanov, N.; FitzGerald, O.; Haglund, E.; Helliwell, P.; Kvien, T.K.; Lories, R.; Luger, T.; Maccarone, M.; Marzo-Ortega, H.; McGonagle, D.; McInnes, I.B.; Olivieri, I.; Pavelka, K.; Schett, G.; Sieper, J.; van den Bosch, F.; Veale, D.J.; Wollenhaupt, J.; Zink, A.; van der Heijde, D. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann. Rheum. Dis., 2016, 75(3), 499-510. doi: 10.1136/annrheumdis-2015-208337 PMID: 26644232
  11. Ritchlin, C.T.; Krueger, J.G. New therapies for psoriasis and psoriatic arthritis. Curr. Opin. Rheumatol., 2016, 28(3), 204-210. doi: 10.1097/BOR.0000000000000274 PMID: 27022911
  12. Cau, Y.; Valensin, D.; Mori, M.; Draghi, S.; Botta, M. Structure, function, involvement in diseases and targeting of 14-3-3 proteins: an update. Curr. Med. Chem., 2018, 25(1), 5-21. doi: 10.2174/0929867324666170426095015 PMID: 28462702
  13. Maksymowych, W.P.; van der Heijde, D.; Allaart, C.F.; Landewé, R.; Boire, G.; Tak, P.P.; Gui, Y.; Ghahary, A.; Kilani, R.; Marotta, A. 14-3-3η is a novel mediator associated with the pathogenesis of rheumatoid arthritis and joint damage. Arthritis Res. Ther., 2014, 16(2), R99. doi: 10.1186/ar4547 PMID: 24751211
  14. Doğan, İ.; Kor, A.; Güven, S.C.; Fırat Oğuz, E.; Başer, S.; Atalar, E.; Maraş, Y.; Erel, Ö.; Erten, Ş. 14–3-3 η ETA protein as a potential marker of joint damage in gout. Clin. Biochem., 2023, 118, 110611. doi: 10.1016/j.clinbiochem.2023.110611 PMID: 37429510
  15. Wang, D.; Cui, Y.; Lei, H.; Cao, D.; Tang, G.; Huang, H.; Yuan, T.; Rao, L.; Mo, B. Diagnostic accuracy of 14-3-3 η protein in rheumatoid arthritis: A meta-analysis. Int. J. Rheum. Dis., 2020, 23(11), 1443-1451. doi: 10.1111/1756-185X.13921 PMID: 32909672
  16. Hammam, N.; Salah, S.; Kholef, E.F.; Moussa, E.M.; Marotta, A. 14-3-3η Protein in serum and synovial fluid correlates with radiographic damage and progression in a longitudinal evaluation of patients with established rheumatoid arthritis. Mod. Rheumatol., 2020, 30(4), 664-670. doi: 10.1080/14397595.2019.1637575 PMID: 31242798
  17. Hu, T.; Liu, Y.; Tan, L.; Huang, J.; Yu, J.; Wu, Y.; Pei, Z.; Zhang, X.; Li, J.; Song, L.; Dai, W.; Xiang, Y. Value of serum collagen triple helix repeat containing-1(CTHRC1) and 14-3-3η protein compared to anti-CCP antibodies and anti-MCV antibodies in the diagnosis of rheumatoid arthritis. Br. J. Biomed. Sci., 2021, 78(2), 67-71. doi: 10.1080/09674845.2020.1810400 PMID: 32813981
  18. Kilani, R.T.; Maksymowych, W.P.; Aitken, A.; Boire, G.; St-Pierre, Y.; Li, Y.; Ghahary, A. Detection of high levels of 2 specific isoforms of 14-3-3 proteins in synovial fluid from patients with joint inflammation. J. Rheumatol., 2007, 34(8), 1650-1657. PMID: 17611984
  19. Wei, J.C.C.; Leong, P.Y.; Liu, G.Y. Chaperone/scaffolding/adaptor protein 14-3-3η (eta): A diagnostic marker of rheumatoid arthritis. Int. J. Rheum. Dis., 2020, 23(11), 1439-1442. doi: 10.1111/1756-185X.14004 PMID: 33225576
  20. Aletaha, D.; Neogi, T.; Silman, A.J.; Funovits, J.; Felson, D.T.; Bingham, C.O., III; Birnbaum, N.S.; Burmester, G.R.; Bykerk, V.P.; Cohen, M.D.; Combe, B.; Costenbader, K.H.; Dougados, M.; Emery, P.; Ferraccioli, G.; Hazes, J.M.W.; Hobbs, K.; Huizinga, T.W.J.; Kavanaugh, A.; Kay, J.; Kvien, T.K.; Laing, T.; Mease, P.; Ménard, H.A.; Moreland, L.W.; Naden, R.L.; Pincus, T.; Smolen, J.S.; Stanislawska-Biernat, E.; Symmons, D.; Tak, P.P.; Upchurch, K.S.; Vencovský, J.; Wolfe, F.; Hawker, G. 2010 rheumatoid arthritis classification criteria: An American college of rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum., 2010, 62(9), 2569-2581. doi: 10.1002/art.27584 PMID: 20872595
  21. Taylor, W.; Gladman, D.; Helliwell, P.; Marchesoni, A.; Mease, P.; Mielants, H.; Group, C.S. Classification criteria for psoriatic arthritis: Development of new criteria from a large international study. Arthritis Rheum., 2006, 54(8), 2665-2673. doi: 10.1002/art.21972 PMID: 16871531
  22. Machado, P.M.; Raychaudhuri, S.P. Disease activity measurements and monitoring in psoriatic arthritis and axial spondyloarthritis. Best Pract. Res. Clin. Rheumatol., 2014, 28(5), 711-728. doi: 10.1016/j.berh.2014.10.004 PMID: 25488780
  23. Nas, K.; Kiliç, E.; Tekeoğlu, İ.; Keskin, Y.; Çevik, R.; Sargin, B.; Acer Kasman, S.; Alkan, H.; Sahin, N.; Cengiz, G.; Cüzdan, N.; Albayrak Gezer, İ.; Keskin, D.; Mülkoglu, C.; Reşorlu, H.; Ataman, Ş.; Bal, A.; Baykul, M.; Duruöz, M.T.; Küçükakkaş, O.; Yurdakul, O.V.; Alkan Melikoğlu, M.; Ayhan, F.F.; Bodur, H.; Çaliş, M.; Çapkin, E.; Devrimsel, G.; Gök, K.; Hizmetli, S.; Kamanlı, A.; Kocabaş, H.; Kutluk, Ö.; Şen, N.; Şendur, Ö.F.; Toprak, M.; Tolu, S.; Tuncer, T. The effect of gender on disease activity and clinical characteristics in patients with axial psoriatic arthritis. Mod. Rheumatol., 2021, 31(4), 869-874. doi: 10.1080/14397595.2020.1812870 PMID: 32820672
  24. Garip, Y.; Eser, F.; Bodur, H. Health-related quality of life in rheumatoid arthritis: comparison of RAQoL with other scales in terms of disease activity, severity of pain, and functional status. Rheumatol. Int., 2011, 31(6), 769-772. doi: 10.1007/s00296-009-1353-1 PMID: 20180124
  25. Anderson, J.; Caplan, L.; Yazdany, J.; Robbins, M.L.; Neogi, T.; Michaud, K.; Saag, K.G.; O’dell, J.R.; Kazi, S. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res. (Hoboken), 2012, 64(5), 640-647. doi: 10.1002/acr.21649 PMID: 22473918
  26. Human 14-3-3 protein eta (YWHAH) ELISA kit. Available from: https://www.cusabio.com/ELISA-Kit/Human-14-3-3-protein-etaYWHAH-ELISA-kit-112977.html#a05
  27. Salman, E.; Çeti̇ner, S.; Boral, B.; Ki̇bar, F.; Erken, E.; Ersözlü, E.D.; Badak, S.Ö.; Bi̇li̇ci̇ Salman, R.; Sertdemi̇r, Y.; Çeti̇n Duran, A.; Yaman, A. Importance of 14-3-3 eta, anti- CarP, and anti-Sa in the diagnosis of seronegative rheumatoid arthritis. Turk. J. Med. Sci., 2019, 49(5), 1498-1502. doi: 10.3906/sag-1812-137 PMID: 31651120
  28. Guan, S.Z.; Yang, Y.Q.; Bai, X.; Wang, Y.; Feng, K.Q.; Zhang, H.J.; Dong, M.; Yang, H.W.; Li, H.Q. Serum 14-3-3η could improve the diagnostic rate of rheumatoid arthritis and correlates to disease activity. Ann. Clin. Lab. Sci., 2019, 49(1), 57-62. PMID: 30814078
  29. Souto-Carneiro, M.; Tóth, L.; Behnisch, R.; Urbach, K.; Klika, K.D.; Carvalho, R.A.; Lorenz, H.M. Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis. Ann. Rheum. Dis., 2020, 79(4), 499-506. doi: 10.1136/annrheumdis-2019-216374 PMID: 32079570
  30. Gong, X.; Xu, S.; Wu, Y.; Ma, C.; Qi, S.; Liu, W.; Xu, J. Elevated serum 14-3-3η protein may be helpful for diagnosis of early rheumatoid arthritis associated with secondary osteoporosis in Chinese population. Clin. Rheumatol., 2017, 36(11), 2581-2587. doi: 10.1007/s10067-017-3807-2 PMID: 28875246
  31. Maksymowych, W.P.; Naides, S.J.; Bykerk, V.; Siminovitch, K.A.; van Schaardenburg, D.; Boers, M.; Landewé, R.; van der Heijde, D.; Tak, P.P.; Genovese, M.C.; Weinblatt, M.E.; Keystone, E.C.; Zhukov, O.S.; Abolhosn, R.W.; Popov, J.M.; Britsemmer, K.; van Kuijk, A.W.; Marotta, A. Serum 14-3-3η is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis. J. Rheumatol., 2014, 41(11), 2104-2113. doi: 10.3899/jrheum.131446 PMID: 25128504
  32. Carrier, N.; Marotta, A.; de Brum-Fernandes, A.J.; Liang, P.; Masetto, A.; Ménard, H.A.; Maksymowych, W.P.; Boire, G. Serum levels of 14-3-3η protein supplement C-reactive protein and rheumatoid arthritis-associated antibodies to predict clinical and radiographic outcomes in a prospective cohort of patients with recent-onset inflammatory polyarthritis. Arthritis Res. Ther., 2016, 18(1), 37. doi: 10.1186/s13075-016-0935-z PMID: 26832367
  33. Qu, C.H.; Hou, Y.; Bi, Y.F.; Han, Q.R.; Jiao, C.H.; Zou, Q.F. Diagnostic values of serum IL-10 and IL-17 in rheumatoid arthritis and their correlation with serum 14-3-3η protein. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(5), 1899-1906. PMID: 30915732
  34. Maksymowych, W.P.; Boire, G.; van Schaardenburg, D.; Wichuk, S.; Turk, S.; Boers, M.; Siminovitch, K.A.; Bykerk, V.; Keystone, E.; Tak, P.P.; van Kuijk, A.W.; Landewé, R.; van der Heijde, D.; Murphy, M.; Marotta, A. 14-3-3η autoantibodies: diagnostic use in early rheumatoid arthritis. J. Rheumatol., 2015, 42(9), 1587-1594. doi: 10.3899/jrheum.141385 PMID: 26178283
  35. Hirata, S.; Marotta, A.; Gui, Y.; Hanami, K.; Tanaka, Y. Serum 14-3-3η level is associated with severity and clinical outcomes of rheumatoid arthritis, and its pretreatment level is predictive of DAS28 remission with tocilizumab. Arthritis Res. Ther., 2015, 17(1), 280. doi: 10.1186/s13075-015-0799-7 PMID: 26449724
  36. Kor, A.; Yalçın, M.; Erten, Ş.; Maraş, Y.; Oğuz, E.F.; Doğan, İ.; Atalar, E.; Başer, S.; Erel, Ö. 14-3-3η proteins as a diagnostic marker, disease activation indicator, and lymphoma predictor in patients with primary sjögren syndrome. Arch. Iran Med., 2023, 26(10), 582-591. doi: 10.34172/aim.2023.85 PMID: 38310415

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers