Skip to main content
  • Original article
  • Open access
  • Published:

Correlation between disease activity and serum interleukin-23 in rheumatoid arthritis

Abstract

Background

Interleukin-23 (IL-23) is a proinflammatory cytokine that is thought to be central to the development of autoimmune diseases.

This study was conducted to determine whether or not serum concentration of IL-23 is elevated in patients with rheumatoid arthritis (RA) and to determine the relationship between the IL-23 level and disease activity in patients with RA.

Patients and methods

Serum samples were obtained from 100 patients with RA and 50 healthy controls. Clinical parameters of the disease were determined, including 28-Joint Disease Activity Score, Clinical Disease Activity Index, Health Assessment Questionnaires, C-reactive protein, rheumatoid factor levels, anti-cyclic citrullinated peptide antibodies, and degree of bony erosions based on radiographs. The levels of IL-23 were determined by enzyme-linked immunosorbent assay (ELISA). The correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined.

Results

Serum IL-23 level was significantly elevated in patients with RA, 0.00–49.30 pg/ml (19.12±13.45 pg/ml) compared with healthy controls, 0.00–1.40 pg/ml (0.90 ±0.63 pg/ml) (P=0.0001). Serum IL-23 levels in patients with RA correlated with Clinical Disease Activity Index (r=0.952, P=0.000), Health Assessment Questionnaires (r=0.953, P=0.000), and 28-Joint Disease Activity Score (r=0.967, P=0.000). Moreover, serum IL-23 levels in patients with RA correlated with erythrocyte sedimentation rate (r=0.950, P=0.000), C-reactive protein (r=0.954, P=0.001), and rheumatoid factor (r=0.917, P=0.000). There was a statistically significant difference between IL-23 mean values associated with different radiograph classes in patients with RA (P=0.001).

Conclusion

Levels of serum IL-23 in patients with RA were significantly higher than in healthy controls. Moreover, elevated serum IL-23 levels were correlated with clinical and laboratory parameters of disease activity. It should be considered as a useful marker to detect active RA. IL-23 is involved in disease progression and bony erosions in patients with RA. Anti-IL-23 drugs could have a potential role in the treatment of RA.

References

  1. Bingham CO III. The pathogenesis of rheumatoid arthritis: pivotal cytokines involved in bone degradation and inflammation. J Rheumatol Suppl 2002; 65:3–9

    CAS  PubMed  Google Scholar 

  2. Brennan FM, McInnes IB. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest 2008; 118:3537–3541

    Article  CAS  Google Scholar 

  3. Paradowska-Gorycka A, Grzybowska-Kowalczyk A, Wojtecka-Lukasik E, Maslinski S. IL-23 in the pathogenesis of rheumatoid arthritis. Scand J Immunol 2010; 71:134–145

    Article  CAS  Google Scholar 

  4. Izcue A, Hue S, Buonocore S. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity 2008; 28:559–570

    Article  CAS  Google Scholar 

  5. Kim HR, Cho ML, Kim KW, Juhn JY, Hwang SY, Yoon CH. Up-regulation of IL-23p19 expression in rheumatoid arthritis synovial fibroblasts by Il-17 through PI3-kinase-, NF-kappa B and p38 MAPK-dependent signaling pathways. Rheumatology 2007; 46:57–64

    Article  CAS  Google Scholar 

  6. Melis L, Vandooren B, Kruithof E, Jacques P, Verbruggen G, De Keyser F, et al. Systemic levels of IL-23 are strongly associated with disease activity in rheumatoid arthritis but not spondylo-arthritis. Ann Rheum Dis 2010; 69:618–623

    Article  CAS  Google Scholar 

  7. Guo YY, Nai-zhi WA, Shuai ZH, Hou L-X., Xu Y-B., Zhang N. Increased interleukin-23 is associated with increased disease activity in patients with rheumatoid arthritis. Chin Med J 2013; 126:850–854

    CAS  PubMed  Google Scholar 

  8. Hillyer P, Larche MJ, Bowman EP, McClanahan TK, de Waal Malefyt R, Schewitz LP, et al. Investigating the role of the interleukin-23/-17A axis in rheumatoid arthritis. Rheumatology (Oxford) 2009; 48:1581–1589

    Article  CAS  Google Scholar 

  9. Kageyama Y, Ichikawa T, Nagafusa T, Torikai E, Shimazu M, Nagano A et al. Etan9recept reduces the serum levels of interleukin-23 and macrophage inflammatory protein-3 alpha in patients with rheumatoid arthritis. Rheumatol Int 2010; 28:137–143

    Article  Google Scholar 

  10. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson T, Bingham CO. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2010; 69:1580–1588

    Article  Google Scholar 

  11. Fransen J, Stucki G, Piet L, Van Riel M. Rheumatoid arthritis measures: Disease Activity Score (DAS), Disease Activity Score-28 (DAS28), Rapid Assessment of Disease Activity in Rheumatology (RADAR), and Rheumatoid Arthritis Disease Activity Index (RADAI). Arthritis Care Res 2003; 49:214–224

    Article  Google Scholar 

  12. Aletaha D, Smolen J. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol 2005; 23:100–110

    Google Scholar 

  13. Lautenschläger J, Mau W, Kohlmann T, Raspe HH, Struve F, Brückle W, et al. Comparative evaluation of the German version of the Health Assessment Questionnaires (HAQ) and functional Questionnaires of Hanover. Z Rheumatol 1997; 56:144–155

    Article  Google Scholar 

  14. Westergren A. Diagnostic tests: the erythrocyte sedimentation rate range and limitations of the technique. Inn Med Kinderheilkunde 1957; 3:20–25

    CAS  Google Scholar 

  15. Shadick NA, Cook NR, Karlson EW, Ridker PM, Maher NE, Manson JE et al. C-reactive protein in the prediction of rheumatoid arthritis in women. Arch Intern Med 2006; 166:2490–2494

    Article  CAS  Google Scholar 

  16. Aho K, Heliovaara M, Maatela J, Berglin E, Padyukov L, Sundin U, et al. Rheumatoid factors antedating clinical rheumatoid arthritis. J Rheumatol 1991; 18:1282

    CAS  PubMed  Google Scholar 

  17. Bizzaro N, Bartoloni E, Gabriella Morozzi G, Stefania Manganelli S, Valeria Riccieri V, Paola Sabatini P, et al. Anti-cyclic citrullinated peptide antibody titer predicts time to rheumatoid arthritis onset in patients with undifferentiated arthritis: results from a 2-year prospective study. Arthritis Res Ther 2013; 15:R16

    Article  CAS  Google Scholar 

  18. Yu X, Abe T, Xiao-Feng S, Ma DX. Enzyme immunoassay for the quantitative determination of human interleukin (IL-23) in human serum, plasma and cell culture supernatants. Clin Exp Immunol 2013; 156: 405–412

    Google Scholar 

  19. Sokka T, Kautiainen H, Hannonen P. Radiographic progression is getting milder in patients with early rheumatoid arthritis. Results of 3 cohorts over 5 years. J Rheumatol 2004; 31:1073–1082

    PubMed  Google Scholar 

  20. Larsen A. How to apply Larsen Score in evaluating radiographs of rheumatoid arthritis in long term studies? J Rheumatol 1995; 22: 1974–1975

    CAS  PubMed  Google Scholar 

  21. Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007; 13:156–63

    Article  CAS  Google Scholar 

  22. Moon SJ, Park JS, Heo YJ, Kang CM, Kim EK, Lim MA. In vivo action of IL-27: reciprocal regulation of Th17 and Treg cells in collagen-induced arthritis. ExpMol Med 2013; 45:46–48

    Google Scholar 

  23. Langrish CL, McKenzie BS, Wilson NJ, Malefyt R, Kastelein RA, Cua DJ. IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol Rev 2004; 202:96–99

    Article  CAS  Google Scholar 

  24. Melis L, Vandooren B, Kruithof E, Jacques P, De Vos M, Mielants H, et al. Systemic levels of IL-23 are strongly associated with disease activity in rheumatoid arthritis but not spondyloarthritis. Ann Rheum Dis 2010; 29:618–623

    Article  Google Scholar 

  25. Rasmussen TK, Andersen T, Hvid M, Hetland ML, Horslev-Petersen K, Stengaard-Pedersen K. Increased interleukin 21 (IL-21) and IL-23 are associated with increased disease activity and with radiographic status in patients with early rheumatoid arthritis. J Rheumatol 2010; 37: 2014–2020

    Article  CAS  Google Scholar 

  26. Duerr KD, Taylor D, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006; 314:1461–1463

    Article  CAS  Google Scholar 

  27. Zaky DS, El-Nahrery M. Role of interleukin-23 as a biomarker in rheumatoid arthritis patients and its correlation with disease activity. Int Immunopharmacol 2016; 31:105–108

    Article  CAS  Google Scholar 

  28. Kageyama Y, Kobayashi H, Kato N. Infliximab treatment reduces the serum levels of interleukin-23 in patients with rheumatoid arthritis. Mod Rheumatol 2009; 19:657–658

    Article  CAS  Google Scholar 

  29. Nistala K, Wedderburn LR. Th17 and regulatory T cells: rebalancing pro- and anti-inflammatory forces in autoimmune arthritis. Rheumatology 2009; 48:602–606

    Article  CAS  Google Scholar 

  30. Elhewala A, Soliman S, Labib A, Mousa W, Salah D. Interleukin-17 level in rheumatoid arthritis patients and its relation to disease activity: a clinical and ultrasound study. Egypt Rheumatol Rehabil 2015; 42:183–184

    Article  Google Scholar 

  31. Chen L, Wei XQ, Evans B, Jiang W, Aeschlimann D. IL-23 promotes osteoclast formation by up-regulation of receptor activator of NF-κB (RANK) expression in myeloid precursor cells. Eur J Immunol 2008; 38:2845–2849

    Article  CAS  Google Scholar 

  32. Siti Dalila A, Shahrir Mohd Said M, Sazliyana Shaharir S, Asrul A, Shah Shamsul A, Sakthiswary R. Interleukin-23 and its correlation with disease activity, joint damage, and functional disability in rheumatoid arthritis. Med Sci 2014; 30:337–342

    Google Scholar 

  33. Guo YY, Wang NZ, Zhao S, Hou LX, Xu YB, Zhang N. Increased interleukin-23 is associated with increased disease activity in patients with rheumatoid arthritis. Chin Med J (Engl) 2013; 126:850–854

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mervat I. Abd Elazeem.

Additional information

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fadda, S.H., Abd Elazeem, M.I., Mohammed, R.A. et al. Correlation between disease activity and serum interleukin-23 in rheumatoid arthritis. Egypt Rheumatol Rehabil 44, 118–124 (2017). https://doi.org/10.4103/err.err_11_17

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/err.err_11_17

Keywords