Skip to main content
SpringerLink
Log in

Circulating level of Th17 cells is associated with sensitivity to glucocorticoids in patients with immune thrombocytopenia

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Glucocorticoids are a widely recognized first-line therapy for immune thrombocytopenia (ITP). However, some patients are unresponsive to glucocorticoid therapy for reasons that remain unclear. Accumulating evidence suggests that CD4+ T-cell abnormalities play a crucial role in the development of ITP. In the present study, we investigated peripheral blood CD4+ T cells, Th17-associated cytokines, and the mRNA expression level of Th17 transcription factor—RORγt—in patients with newly-diagnosed ITP before glucocorticoid therapy. The study involved 27 newly-diagnosed patients. Th17-cell levels in the peripheral blood of newly-diagnosed ITP patients were associated with responsiveness to glucocorticoid therapy. Newly-diagnosed ITP patients who were not sensitive to glucocorticoid treatment were found to have lower levels of Th17 cells. Quantifying Th17 cells may allow physicians to predict prognosis of glucocorticoid treatment and stratify therapy for those with ITP. This strategy may provide a new approach to the treatment of glucocorticoid-insensitive patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113:2386–93.

    Article  CAS  PubMed  Google Scholar 

  2. Barsam SJ, Psaila B, Forestier M, Page LK, Sloane PA, Geyer JT, et al. Platelet production and platelet destruction: assessing mechanisms of treatment effect in immune thrombocytopenia. Blood. 2011;117:5723–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Johnsen J. Pathogenesis in immune thrombocytopenia: new insights. Hematol Am Soc Hematol Educ Program. 2012;2012:306–12.

    Google Scholar 

  4. Guo L, Kapur R, Aslam R, Speck ER, Zufferey A, Zhao Y, et al. CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell-mediated immune thrombocytopenia. Blood. 2016;127:735–8.

    Article  CAS  PubMed  Google Scholar 

  5. Ji X, Zhang L, Peng J, Hou M. T cell immune abnormalities in immune thrombocytopenia. J Hematol Oncol. 2014;7:72.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zhao Z, Yang L, Yang G, Zhuang Y, Qian X, Zhou X, et al. Contributions of T lymphocyte abnormalities to therapeutic outcomes in newly diagnosed patients with immune thrombocytopenia. PLoS One. 2015;10:e0126601.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hu Y, Wang X, Yu S, Hou Y, Ma D, Hou M. Neutralizations of IL-17A and IL-21 regulate regulatory T cell/T-helper 17 imbalance via T-helper 17-associated signaling pathway in immune thrombocytopenia. Expert Opin Ther Targets. 2015;19:723–32.

    Article  CAS  PubMed  Google Scholar 

  8. Ji L, Zhan Y, Hua F, Li F, Zou S, Wang W, et al. The ratio of Treg/Th17 cells correlates with the disease activity of primary immune thrombocytopenia. PLoS One. 2012;7:e50909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu H, Ouyang X, Li Y, Zeng H, Wang X, Xie S, et al. Involvement of levels of Toll like receptor-4 in monocytes, CD4+ T-lymphocyte subsets, and cytokines in patients with immune thrombocytopenic purpura. Thromb Res. 2013;132:196–201.

    Article  CAS  PubMed  Google Scholar 

  10. Li J, Wang Z, Hu S, Zhao X, Cao L. Correction of abnormal T cell subsets by high-dose dexamethasone in patients with chronic idiopathic thrombocytopenic purpura. Immunol Lett. 2013;154:42–8.

    Article  CAS  PubMed  Google Scholar 

  11. Singh RP, Hasan S, Sharma S, Nagra S, Yamaguchi DT, Wong DT, et al. Th17 cells in inflammation and autoimmunity. Autoimmun Rev. 2014;13:1174–81.

    Article  CAS  PubMed  Google Scholar 

  12. Mitsdoerffer M, Lee Y, Jager A, Kim HJ, Korn T, Kolls JK, et al. Proinflammatory T helper type 17 cells are effective B-cell helpers. Proc Natl Acad Sci USA. 2010;107:14292–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nishimoto T, Kuwana M. CD4+CD25+Foxp3+ regulatory T cells in the pathophysiology of immune thrombocytopenia. Semin Hematol. 2013;50(Suppl 1):S43–9.

    Article  CAS  PubMed  Google Scholar 

  14. Yazdanbakhsh K, Zhong H, Bao W. Immune dysregulation in immune thrombocytopenia. Semin Hematol. 2013;50(Suppl 1):S63–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Perera M, Garrido T. Advances in the pathophysiology of primary immune thrombocytopenia. Hematology. 2017;22:41–53.

    Article  CAS  PubMed  Google Scholar 

  16. Jernas M, Hou Y, Stromberg Celind F, Shao L, Nookaew I, Wang Q, et al. Differences in gene expression and cytokine levels between newly diagnosed and chronic pediatric ITP. Blood. 2013;122:1789–92.

    Article  PubMed  Google Scholar 

  17. Wei Y, Hou M. T cells in the pathogenesis of immune thrombocytopenia. Semin Hematol. 2016;53(Suppl 1):S13–5.

    Article  PubMed  Google Scholar 

  18. Leon B, Ballesteros-Tato A, Lund FE. Dendritic cells and B cells: unexpected partners in Th2 development. J Immunol. 2014;193:1531–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Maddur MS, Sharma M, Hegde P, Stephen-Victor E, Pulendran B, Kaveri SV, et al. Human B cells induce dendritic cell maturation and favour Th2 polarization by inducing OX-40 ligand. Nat Commun. 2014;5:4092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nomura S. Advances in diagnosis and treatments for immune thrombocytopenia. Clin Med Insights Blood Disord. 2016;9:15–22.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gudbrandsdottir S, Birgens HS, Frederiksen H, Jensen BA, Jensen MK, Kjeldsen L, et al. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood. 2013;121:1976–81.

    Article  CAS  PubMed  Google Scholar 

  22. Sollazzo DTS, Curti A, Vianelli N, Lemoli RM, Catani L. Circulating CD4+CD161+CD196+ Th17 cells are not increased in immune thrombocytopenia. Haematologica. 2011;96:632–4.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Cao J, Chen C, Li L, Ling-yu Z, Zhen-yu L, Zhi-ling Y, et al. Effects of high-dose dexamethasone on regulating interleukin-22 production and correcting Th1 and Th22 polarization in immune thrombocytopenia. J Clin Immunol. 2012;32:523–9.

    Article  CAS  PubMed  Google Scholar 

  24. Rocha AM, Souza C, Rocha GA, de Melo FF, Clementino NC, Marino MC, et al. The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia. Haematologica. 2011;96:1560–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhou L, Xu F, Chang C, Tao Y, Song L, Li X. Interleukin-17-producing CD4+ T lymphocytes are increased in patients with primary immune thrombocytopenia. Blood Coagul Fibrinolysis. 2016;27:301–7.

    Article  CAS  PubMed  Google Scholar 

  26. Rocha AM, Souza C, Rocha GA, de Melo FF, Clementino NC, Marino MC, et al. The serum levels of the cytokines involved in the Th17 and Th1 cell commitment are increased in individuals with borderline thrombocytopenia. J Hematol Oncol. 2013;6:28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yu S, Liu C, Li L, Tian T, Wang M, Hu Y, et al. Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia. Lab Investig. 2015;95:157–67.

    Article  CAS  PubMed  Google Scholar 

  28. Ye X, Zhang L, Wang H, Chen Y, Zhang W, Zhu R, et al. The role of IL-23/Th17 pathway in patients with primary immune thrombocytopenia. PLoS One. 2015;10:e0117704.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cao J, Chen C, Zeng L, Li L, Li X, Li Z, et al. Elevated plasma IL-22 levels correlated with Th1 and Th22 cells in patients with immune thrombocytopenia. Clin Immunol. 2011;141:121–3.

    Article  CAS  PubMed  Google Scholar 

  30. Nishimoto T, Satoh T, Takeuchi T, Ikeda Y, Kuwana M. Critical role of CD4(+)CD25(+) regulatory T cells in preventing murine autoantibody-mediated thrombocytopenia. Exp Hematol. 2012;40:279–89.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (311371399).

Author information

Author notes

  1. Y. Zhang and T. Ma contributed equally to this work.

Authors and Affiliations

  1. Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China

    YiChan Zhang, TingTing Ma, Xuan Zhou & Juan Li

  2. Department of Laboratory, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China

    JunHao Chen

Authors
  1. YiChan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. TingTing Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xuan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. JunHao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LJ, CJH, MTT, and ZYC conceived and designed the study. MTT, ZYC, and ZX performed the experiments. ZYC and MTT wrote the paper. LJ reviewed and edited the manuscript. All authors read and approved the manuscript.

Corresponding authors

Correspondence to JunHao Chen or Juan Li.

Ethics declarations

Conflict of interest

All authors declare no conflict of interest.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Ma, T., Zhou, X. et al. Circulating level of Th17 cells is associated with sensitivity to glucocorticoids in patients with immune thrombocytopenia. Int J Hematol 107, 442–450 (2018). https://doi.org/10.1007/s12185-017-2392-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-017-2392-0

Keywords

Search

Navigation