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Interleukin-17 in Behçet’s disease: relation with clinical picture and disease activity

Abstract

Aim

The aim of this study was to assess serum levels of interleukin-17 (IL-17) in patients with Behçet’s disease (BD) and to evaluate its relation to the clinical picture and disease activity.

Patients and methods

This case-control study was carried out on 38 patients with BD. A total of 20 age-matched and sex-matched healthy volunteers serving as the control group were also enrolled in this study. All patients were subjected to full history taking, thorough clinical examination, and clinical activity assessment using Behçet’s Disease Current Activity Form. Serum IL-17 levels were measured with enzyme-linked immunosorbent assay.

Results

Serum IL-17 levels were significantly elevated among BD patients. Patients with ocular involvement had higher IL-17 levels compared with those without; however, the difference did not reach statistical significance. Patients with neurological involvement had significantly higher IL-17 levels in their serum compared with those without neurological involvement and controls. Twenty-seven patients had active disease, whereas 11 patients had inactive disease. Serum IL-17 levels were significantly elevated in active BD patients. Patients with and without activity showed highly significant rise in IL-17 levels compared with healthy controls. There was no significant correlation between the amount of corticosteroids or colchicine being used and serum IL-17 levels.

Conclusion

IL-17 is elevated among BD patients and further increased with activity, ocular affection, and neuroinvolvement. Our findings suggest that IL-17 exerts an important role in the pathogenesis of BD, thus providing a promising target for novel therapy.

References

  1. Mat MC, Sevim A, Fresko I, Tüzün Y. Behçet’s disease as a systemic disease. Clin Dermatol 2014; 32:435–442.

    Article  Google Scholar 

  2. Chi W, Zhu X, Yang P, Liu X, Lin X, Zhou H, et al. Upregulated IL-23 and IL-17 in Behçet patients with active uveitis. Invest Ophthalmol Vis Sci 2008; 49:3058–3064.

    Article  Google Scholar 

  3. Truchetet ME, Mossalayi MD, Boniface K. IL-17 in the rheumatologist’s line of sight. Biomed Res Int 2013; 2013:295132.

    Article  Google Scholar 

  4. Direskeneli H, Fujita H, Akdis CA. Regulation of TH17 and regulatory T cells in patients with Behçet disease. J Allergy Clin Immunol 2011; 128:665–666.

    Article  CAS  Google Scholar 

  5. Oh K, Byoun OJ, Ham DI, Kim YS, Lee DS. Invariant NKT cells regulate experimental autoimmune uveitis through inhibition of Th17 differentiation. Eur J Immunol 2011; 41:392–402.

    Article  CAS  Google Scholar 

  6. Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol 2003; 171:6173–6177.

    Article  CAS  Google Scholar 

  7. Iwakura Y, Nakae S, Saijo S, Ishigame H. The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol Rev 2008; 226:57–79.

    Article  CAS  Google Scholar 

  8. Witowski J, Ksiazek K, Jorres A. Interleukin-17: a mediator of inflammatory responses. Cell Mol Life Sci 2004; 61:567–579.

    Article  CAS  Google Scholar 

  9. Hamzaoui K, Borhani Haghighi A, Ghorbel IB, Houman H. RORC and Foxp3 axis in cerebrospinal fluid of patients with neuro-Behcet’s disease. J Neuroimmunol 2011; 233:249–253.

    Article  CAS  Google Scholar 

  10. Van den Berg WB, McInnes IB. Th17 cells and IL-17A Focus on immunopathogenesis and immunotherapeutics. Semin Arthritis Rheum 2013; 43:158–170.

    Article  Google Scholar 

  11. Leng RX, Chen GM, Pan HF, Ye DQ. The role of IL-23/IL-17 axis in the etiopathogenesis of Behçet’s disease. Clin Rheumatol 2010; 29:1209.

    Article  Google Scholar 

  12. Zhou ZY, Chen SL, Shen N, Lu Y. Cytokines and Behcet’s disease. Autoimmun Rev 2012; 11:699–704.

    Article  CAS  Google Scholar 

  13. International Study Group for Behçet’s disease. Criteria for diagnosis of Behcet’s disease. Lancet 1990; 335:1078–1080.

    Google Scholar 

  14. Altaç M, Tüzün Y, Yurdakul S, Binyildiz P, Yazici H. The validity of the pathergy test (non-specific skin hyperreactivity) in Behçet’s disease: a double-blind study by independent observers. Acta Derm Venereol 1982; 62:158–159.

    PubMed  Google Scholar 

  15. Bhakta BB, Brennan P, James TE, Chamberlain MA, Noble BA, Silman AJ. Behçet’s disease: evaluation of a new instrument to measure clinical activity. Rheumatology 1999; 38:728–733.

    Article  CAS  Google Scholar 

  16. Han EC, Cho SB, Ahn KJ, Oh SH, Kim J, Kim DS, et al. Expression of pro-inflammatory protein S100A12 (EN-RAGE) in Behçet’s disease and its association with disease activity: a pilot study. Ann Dermatol 2011; 23:313–320.

    Article  CAS  Google Scholar 

  17. Peño IC, de las Heras Revilla V, Carbonell BP, di Capua Sacoto D, Ferrer ME, García-Cobos R, González RA. Neurobehçet disease: clinical and demographic characteristics. Eur J Neurol 2012; 19:1224–1227.

    Article  Google Scholar 

  18. Sugita S, Kawazoe Y, Imai A, Kawaguchi T, Horie S, Keino H, et al. Role of IL-22 and TNF-α producing Th22 cells in uveitis patients with Behçet’s disease. J Immunol 2013; 190:5799–5808.

    Article  CAS  Google Scholar 

  19. Zare Shahneh F, Mohammadian M, Babaloo Z, Baradaran B. New approaches in immunotherapy of Behçet disease. Adv Pharm Bull 2013; 3:9–11.

    PubMed  PubMed Central  Google Scholar 

  20. Neves FS, Spiller F. Possible mechanisms of neutrophil activation in Behçet’s disease. Int Immunopharmacol 2013; 17:1206–1210.

    Article  CAS  Google Scholar 

  21. Moseley TA, Haudenschild DR, Rose L, Reddi AH. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev 2003; 14:155–174.

    Article  CAS  Google Scholar 

  22. Chi W, Yang P, Zhu X, Wang Y, Chen L, Huang X, Liu X. Production of interleukin-17 in Behçet’s disease is inhibited by cyclosporin A. Mol Vis 2010; 19:880–886.

    Google Scholar 

  23. Hamzaoui K, Hamzaoui A, Guemira F, Bessioud M, Hamza M, Ayed K. Cytokine profile in Behçet’s disease patients. Relationship with disease activity. Scand J Rheumatol 2002; 31:205–210.

    Article  Google Scholar 

  24. Takeuchi, M, Y Usui, Y Okunuki, L Zhang, J Ma, N Yamakawa, et al. Immune responses to interphotoreceptor retinoid-binding protein and S-antigen in Behcet’s patients with uveitis. Invest Ophthalmol Vis Sci 2010; 51:3067–3075.

    Article  Google Scholar 

  25. Shimizu J, Takai K, Fujiwara N, Arimitsu N, Ueda Y, Wakisaka S, et al. Excessive CD4+ T cells co-expressing interleukin-17 and interferon-γ in patients with Behçet’s disease. Clin Exp Immunol 2012; 168:68–74.

    Article  CAS  Google Scholar 

  26. Kim J, Park JA, Lee EY, Lee YJ, Song YW, Lee EB. Imbalance of Th17 to Th1 cells in Behçet’s disease. Clin Exp Rheumatol 2010; 28:S16–S19.

    PubMed  Google Scholar 

  27. Chen Q, Yang W, Gupta S, Biswas P, Smith P, Bhagat G, Pernis AB. IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor. Immunity 2008; 29:899–911.

    Article  CAS  Google Scholar 

  28. Jang WC, Nam YH, Ahn YC, Lee SH, Park SH, Choe JY, et al. Interleukin-17F gene polymorphisms in Korean patients with Behçet’s disease. Rheumatol Int 2008; 29:173–178.

    Article  CAS  Google Scholar 

  29. Geri G, Terrier B, Rosenzwajg M, Wechsler B, Touzot M, Seilhean D, et al. Critical role of IL-21 in modulating TH17 and regulatory T cells in Behçet disease. J Allergy Clin Immunol 2011; 128:655–664.

    Article  CAS  Google Scholar 

  30. Wang C, Tian Y, Ye Z, Kijlstra A, Zhou Y, Yang P. Decreased interleukin-27 expression is associated with active uveitis in Behçet’s disease. Arthritis Res Ther 2014; 16:R117.

    Article  Google Scholar 

  31. Na SY, Park MJ, Park S, Lee ES. Up-regulation of Th17 and related cytokines in Behçet’s disease corresponding to disease activity. Clin Exp Rheumatol 2013; 31:32–40.

    PubMed  Google Scholar 

  32. Pineton de Chambrun M, Wechsler B, Geri G, Cacoub P, Saadoun D. New insights into the pathogenesis of Behçet’s disease. Autoimmun Rev 2012; 11:687–698.

    Article  CAS  Google Scholar 

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Correspondence to Dina S. Al-Zifzaf MD.

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Al-Zifzaf, D.S., Mokbel, A.N. & Abdelaziz, D.M. Interleukin-17 in Behçet’s disease: relation with clinical picture and disease activity. Egypt Rheumatol Rehabil 42, 34–38 (2015). https://doi.org/10.4103/1110-161X.155646

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  • DOI: https://doi.org/10.4103/1110-161X.155646

Keywords

  • Behçet’s disease
  • interleukin-17
  • neuro-Behçet
  • ocular-Behçet