Skip to main content
Egyptian Rheumatology and Rehabilitation
Download PDF
  • Original article
  • Open access
  • Published:

Clinical significance of interleukin 27 serum concentration in patients with systemic sclerosis: relation to clinical, laboratory and radiological parameters

Egyptian Rheumatology and Rehabilitation volume 46, pages 101–107 (2019)Cite this article

Abstract

Background

Interleukin 27 (IL27) is a cytokine that belongs to IL12 family and it is mainly produced by antigen presenting cells. IL27 binding to its receptor leads to activation of many intracellular signaling pathways that can exhibit a wide variety of immunomodulatory actions.

Aim of the work

The current study aimed to determine IL27 concentrations in the sera of SSc patients and to assess the relation between these concentrations and the various clinical, laboratory and radiological disease parameters.

Methods

We measured serum IL27 concentrations in 31 SSc patients and 20 controls. The patients were subjected to detailed history and clinical evaluation. In SSc patients, modified Rodnan skin score (MRSS) was used to assess the skin thickness and pulmonary involvement was assessed by high resolution computerized tomography (HRCT) and forced vital capacity (FVC) assessment.

Results

IL27 serum concentrations in diffuse (median, 302.8; 101.6-1034.4 ng/L) and limited (median, 385; 109-826.3 ng/L) subtypes of SSc showed a significant elevation (P < 0.001) compared to its concentrations in the controls (median, 104.2; 51-184.2 ng/L). SSc patients with elevated IL27 serum concentrations had significantly lower forced vital capacity (FVC) than those with normal IL27 serum concentrations (p=0.04). Also, serum level of sCD163 significantly correlated with MRSS (r=0.48, p=0.0064) and FVC (r=-0.6, p=0.0005).

Conclusion

Patients with systemic sclerosis have significantly increased serum IL27 concentrations that remarkably associated with significant cutaneous and pulmonary involvement signifying that it could be a beneficial biomarker that reflects disease severity and implies a possible pathogenic role in SSc.

References

  1. Nihtyanova SI, Ong VH, Denton CP. Current management strategies for systemic sclerosis. Clin Exp Rheumatol 2014; 32 (Suppl 81):156–164.

    PubMed  Google Scholar 

  2. Pattanaik D, Brown M, Postlethwaite BC, Postlethwaite AE. Pathogenesis of systemic sclerosis. Front Immunol 2015; 6:272.

    Article  Google Scholar 

  3. Altorok N, Kahaleh B. Epigenetics and systemic sclerosis. Semin Immunopathol 2015; 37:453–462.

    Article  CAS  Google Scholar 

  4. Asano Y. Systemic sclerosis. J Dermatol 2018; 45:128–138.

    Article  Google Scholar 

  5. Raker V, Haub J, Stojanovic A, Cerwenka A, Schuppan D, Steinbrink K. Early inflammatory players in cutanous fibrosis. J Dermatol Sci 2017; 87:228–235.

    Article  CAS  Google Scholar 

  6. Dowson C, Simpson N, Duffy L, O’Reilly S. Innate immunity in systemic sclerosis. Curr Rheumatol Rep 2017; 19:2.

    Article  Google Scholar 

  7. Yoshida H, Hunter CA. The immunobiology of interleukin-27. Annu Rev Immunol 2015; 33:417–443.

    Article  CAS  Google Scholar 

  8. Wittmann M, Zeitvogel J, Wang D, Werfel T. IL-27 is expressed in chronic human eczematous skin lesions and stimulates human keratinocytes. J Allergy Clin Immunol 2009; 124:81–89.

    Article  CAS  Google Scholar 

  9. Kimura D, Miyakoda M, Kimura K, Honma K, Hara H, Yoshida H, et al. Interleukin 27 producing CD4(+) T cells regulate protective immunity during malaria parasite infection. Immunity 2016; 44:672–682.

    Article  CAS  Google Scholar 

  10. Meka RR, Venkatesha SH, Dudics S, Acharya B, Moudgil KD. IL-27-induced modulation of autoimmunity and its therapeutic potential. Autoimmun Rev 2015; 14:1131–1141.

    Article  CAS  Google Scholar 

  11. Wang J, Wang G, Sun B, Li H, Mu L, Wang Q, et al. Interleukin-27 suppresses experimental autoimmune encephalomyelitis during bone marrow stromal cell treatment. J Autoimmun 2008; 30:222–229.

    Article  CAS  Google Scholar 

  12. Shen H, Xia L, Xiao W, Lu J. Increased levels of interleukin-27 in patients with rheumatoid arthritis. Arthritis Rheum 2011; 63:860–861.

    Article  CAS  Google Scholar 

  13. Duarte AL, Dantas AT, de Ataíde Mariz H, dos Santos FA, da Silva JC, da Rocha LF Jr, et al. Decreased serum interleukin 27 in Brazilian systemic lupus erythematosus patients. Mol Biol Rep 2013; 40:4889–4892.

    Article  CAS  Google Scholar 

  14. Yoshizaki A, Yanaba K, Iwata Y, Komura K, Ogawa A, Muroi E, et al. Elevated serum interleukin-27 levels in patients with systemic sclerosis: association with T cell, B cell and fibroblast activation. Ann Rheum Dis 2011; 70:194–200.

    Article  CAS  Google Scholar 

  15. Shibata S, Tada Y, Kanda N, Nashiro K, Kamata M, Karakawa M, et al. Possible roles of IL-27 in the pathogenesis of psoriasis. J Invest Dermatol 2010; 130:1034–1039.

    Article  CAS  Google Scholar 

  16. Iwasaki Y, Fujio K, Okamura T, Yamamoto K. Interleukin-27 in T cell immunity. Int J Mol Sci 2015; 16:2851–2863.

    Article  CAS  Google Scholar 

  17. Huber M, Steinwald V, Guralnik A, Brüstle A, Kleemann P, Rosenplänter C, et al. IL-27 inhibits the development of regulatory T cells via STAT3. Int Immunol 2008; 20:223–234.

    Article  CAS  Google Scholar 

  18. Yoshimoto T, Okada K, Morishima N, Kamiya S, Owaki T,Asakawa M, et al. Induction of IgG2a class switching in B cells by IL-27. J Immunol 2004; 173:2479–2485.

    Article  CAS  Google Scholar 

  19. Van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Arthritis Rheum 2013; 65:2737–2747.

    Article  Google Scholar 

  20. Le Roy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger JrTA, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988; 15:202–205.

    Google Scholar 

  21. Steen VD, Medsger TA Jr. Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum 2000; 43:2437–2444.

    Article  CAS  Google Scholar 

  22. Clements P, Lachenbruch P, Seibold J, White B, Weiner S, Martin R, et al. Inter- and intraobserver variability of total skin thickness score (modified Rodan TSS) in systemic sclerosis. J Rheumatol 1995; 22:1281–1285.

    CAS  PubMed  Google Scholar 

  23. Sakkas LI, Chikanza IC, Platsoucas CD. Mechanismsofdisease: the role of immune cells in the pathogenesis of systemic sclerosis. Nat Clin Pract Rheumatol 2006; 2:679–685.

    Article  CAS  Google Scholar 

  24. Kalogerou A, Gelou E, Mountantonakis S, Settas L, Zafiriou E, Sakkas L. Early T cell activation in the skin from patients with systemic sclerosis. Ann Rheum Dis 2005; 64:1233–1235.

    Article  CAS  Google Scholar 

  25. Sakkas LI, Platsoucas CD. Is systemic sclerosis an antigen-driven T cell disease? Arthritis Rheum 2004; 50:1721–1733.

    Article  CAS  Google Scholar 

  26. Abraham DJ, Varga J. Scleroderma: from cell and molecular mechanisms to disease models. Trends Immunol 2005; 26:587–595.

    Article  CAS  Google Scholar 

  27. Aparicio-Siegmund S, Garbers C. The biology of interleukin-27 reveals unique pro- and anti-inflammatory functions in immunity. Cytokine Growth Factor Rev 2015; 26:579–586.

    Article  CAS  Google Scholar 

  28. Pflanz S, Hibbert L, Mattson J, Rosales R, Vaisberg E, Bazan JF, et al. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J Immunol 2004; 172:2225–2231.

    Article  CAS  Google Scholar 

  29. Kopiński P, Wandtke T, Dyczek A, Wędrowska E, Roży A, Senderek T, et al. Increased levels of interleukin 27 in patients with early clinical stages of non-small cell lung cancer. Pol Arch Intern Med 2018; 128:105–114.

    PubMed  Google Scholar 

  30. Su Y, Yao H, Wang H, Xu F, Li D, Li D, et al. IL27 enhances innate immunity of human pulmonary fibroblasts and epithelial cells through upregulation of TLR4 expression. Am J Physiol Lung Cell Mol Physiol 2016; 310: L133–L141.

    Article  Google Scholar 

  31. Dong Z, Lu X, Yang Y, Zhang T, Li Y, Chai Y, et al. IL-27 alleviates the bleomycin-induced pulmonary fibrosis by regulating the Th17 cell differentiation. BMC Pulm Med 2015; 15:13.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Rheumatology, Rehabilitation and Physical Medicine, Benha University, Benha, 13516, Egypt

    Waleed A. Hassan MD, Gamal A. Hamaad & Emtethal A. Sayed

  2. Department of Clinical and Chemical Pathology and Immunology, Benha University, Benha, Egypt

    Mona M. El Behisy

  3. Department of Rheumatology, and Rehabilitation, Minya Elkamh Hospital, Minya Elkamh, Egypt

    Manal K. Gomaa

Authors
  1. Waleed A. Hassan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gamal A. Hamaad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emtethal A. Sayed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mona M. El Behisy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Manal K. Gomaa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Waleed A. Hassan MD.

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 noncommercially, 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

Hassan, W.A., Hamaad, G.A., Sayed, E.A. et al. Clinical significance of interleukin 27 serum concentration in patients with systemic sclerosis: relation to clinical, laboratory and radiological parameters. Egypt Rheumatol Rehabil 46, 101–107 (2019). https://doi.org/10.4103/err.err_63_18

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/err.err_63_18

Keywords