Skip to main content

Advertisement

SpringerLink
Log in

Differential Expression of T-bet and GATA3 in Egyptian Children with Idiopathic Thrombocytopenic Purpura

  • Original Article
  • Published:
Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

GATA3 and T-box (T-bet) expressed in T-cells are transcriptional factors that play a critical role in development of Th2 and Th1 immunity respectively. GATA3 is expressed during Th2 differentiation and T-bet is expressed exclusively in Th1 cells. Thus, a balance between GATA3 and T-bet is believed to control Th2/Th1 polarization. Therefore, the high expression of T-bet and low expression of GATA3 indicate the existence of Th1 polarization in children with acute immune thrombocytopenic purpura (ITP). This might be related to the regulation of T-bet and GATA3. The objective of this work was to study the expression of transcriptional factors T-bet and GATA3 m RNA in children with idiopathic thrombocytopenic purpura and correlate it with clinical findings, laboratory findings, and outcome of patients. In this study the expression of T-bet and GATA3 genes was analysed in 20 normal healthy individuals and 40 children with ITP (20 acute and 20 persistent) using reverse transcriptase polymerase chain reaction to investigate a possible relation, association or correlation with the type of ITP and prognosis. T-bet was expressed significantly in 60 % of acute ITP children (12/20) (P value 0.001) and not expressed in persistent ITP children (0/20), while GATA3 was expressed in 25 % of persistent ITP patients (5/20) (P value 0.017) and not expressed in acute ITP patients (0/20). Both genes were not detected in healthy controls. We concluded that the high expression of T-bet and the low expression of GATA3 indicate the existence of Th1 polarization in children with acute ITP. This might be related to the regulation of T-bet and GATA3. Intensive studies of abnormal cytokine profiles in ITP have led to cytokine therapies that exploit the effects of IFN-γ on Th2 cells, but such therapies are often ineffective to develop safe and effective therapeutic tools. Targeting specific molecules such as T-bet and GATA3 may be a novel therapeutic tool in ITP.

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

Similar content being viewed by others

References

  1. Coopamah M, Garvey M, Freedman J, Semple J (2003) Cellular immune mechanisms in autoimmune thrombocytopenic purpura: an update. Transfus Med Rev 17(1):69–80

    Article  PubMed  Google Scholar 

  2. Schwartz RS (2007) Immune thrombocytopenic purpura-from agony to agonist. N Engl J Med 357(22):2299–2301

    Article  CAS  PubMed  Google Scholar 

  3. Stasi R, Newland AC (2011) ITP: a historical perspective. Br J Haematol 153(4):437–450

    Article  PubMed  Google Scholar 

  4. Wang J, Wiley JM, Luddy R, Greenberg J, Feuerstein MA, Bussel JB (2005) Persistent immune thrombocytopenic purpura in children: assessment of rituximab treatment. J Pediatr 146:217–221

    Article  CAS  PubMed  Google Scholar 

  5. Arakawo S, Hatano Y, Katagiri K (2004) Differential expression of mRNA for Th1 and Th2 cytokine associated transcriptional factors and suppressors of cytokine signaling in peripheral blood mononuclear cells of patients with atopic dermatitis. Clin Exp Immunol 135(3):505–510

    Article  Google Scholar 

  6. Afkarian M, Sedy JR, Yang J (2002) T-bet is a STAT1-induced regulator for IL-12 R expression in naïve CD4+ T-cells. Nat Immunol 3(6):549–557

    Article  CAS  PubMed  Google Scholar 

  7. Lugo-Villarino G, Maldonado-López R, Possemato R, Peñaranda C, Glimcher LH (2003) T-bet is required for optimal production of IFNγ and antigen-specific T-cell activation by dendritic cells. Proc Natl Acad Sci USA 100(13):7749–7754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lazarevic V, Chen X, Shim JH (2011) T-bet represses TH 17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt. Nat Immunol 12(1):96–104

    Article  CAS  PubMed  Google Scholar 

  9. Djuretic IM, Levanon D, Negreanu V, Groner Rao A, Ansel KM (2007) Transcription factors T-bet and RUNX3 cooperate to activate IFNγ and silence IL-4 in T helper type 1 cells. Nat Immunol 8(2):145–153

    Article  CAS  PubMed  Google Scholar 

  10. Zhu J, Guo L, Watson CJ, Hu-Li J, Paul WE (2001) STAT6 is necessary and sufficient for IL-4’s role in TH2 differentiation and cell expansion. J Immunol 166(12):7276–7281

    Article  CAS  PubMed  Google Scholar 

  11. Zhu J, Yamane H, Cote-Sierra J, Guo L, Paul WE (2006) GATA3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cellspecific factors. Cell Res 16(1):3–10

    Article  CAS  PubMed  Google Scholar 

  12. Usui T, Nishikomori R, Kitani A, Strober W (2003) GATA3 suppresses Th1 development by down-regulation of Stat4 and not through effects on IL-12Rβ2 chain or T-bet. Immunity 18(3):415–428

    Article  CAS  PubMed  Google Scholar 

  13. Rodeghiero F, Stasi R, Gernsheimer T et al (2009) Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura (ITP) of adults and children. Report from an international working group. Blood 113:2386–2393

    Article  CAS  PubMed  Google Scholar 

  14. Kuhen T (2013) Update of the international co-operative ITP study (ICIS)and on the pediatric and adult registry on persistent ITP(PARC ITP). Pediatr Blood Cancer 60:S15–S18

    Article  Google Scholar 

  15. World Medical Association. Declaration of Helsinki (2008) Ethical principles for medical research involving human subjects. In: The 59th WMA General Assembly, Seoul, South Korea

  16. Cooper N, Bussel J (2006) The pathogenesis of immune thrombocytopaenic purpura. Br J Haematol 133(4):364–374

    Article  CAS  PubMed  Google Scholar 

  17. Cines DB, Bussel JB, Liebman HA et al (2009) The ITP syndrome: pathogenic and clinical diversity. Blood 113(26):6511–6521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bergmann AK, Grace RF, Neufeld EJ (2010) Genetic studies in pediatric ITP: outlook, feasibility, and requirements. Ann Hematol 89(Suppl 1):S95–S103

    Article  PubMed  PubMed Central  Google Scholar 

  19. Breunis WB, van Mirre E, Bruin M et al (2008) Copy number variation of the activating FCGR2C gene predisposes to idiopathic thrombocytopenic purpura. Blood 111(3):1029–1038

    Article  CAS  PubMed  Google Scholar 

  20. Ho IC, Glimcher LH (2002) Transription, initializing times for T cells. Cell 109(Suppl):S109–S120

    Article  CAS  PubMed  Google Scholar 

  21. Ouyang W, Ranganath SH, Weindel K et al (1998) Inhibition of Th1 development mediated by GATA-3 through an IL-4 independent mechanism. Immunity 9:745–755

    Article  CAS  PubMed  Google Scholar 

  22. Bian T, Yin K, Jin S et al (2006) Treatment of allergic airway inflammation and hyperresponsiveness by imiquimod modulating transcription factors T-bet and GATA-3. Chin Med J 119(8):640–648

    CAS  PubMed  Google Scholar 

  23. Rengarajan J, Szabos J, Glimcher LH (2000) Transcriptional regulation of Th1/Th2 polarization. Immunol Today 21:479–483

    Article  CAS  PubMed  Google Scholar 

  24. Lee GR, Fields PE, Flavell RA (2001) Regulation of IL-4 gene expression by distal regulatory elements and GATA3 at the chromatin level. Immunity 14:447–459

    Article  CAS  PubMed  Google Scholar 

  25. Zhang DH, Yang L, Ray A (1998) Differential responsiveness of the IL-5 & IL-4 genes to transcriptional factor GATA-3. J Immunol 161:3817–3821

    CAS  PubMed  Google Scholar 

  26. Finotto S, Neurath MF, Glickman JN et al (2002) Development of spontaneous air way changes consistent with human asthma in mice lacking T-bet. Science 295:336–338

    Article  CAS  PubMed  Google Scholar 

  27. Szabo DH, Sullivan BM, Stemmann C et al (2002) Distinct effects of T-bet in Th1 lineage commitment and IFN-production in CD4 and CD8 T cells. Science 295:338–342

    Article  CAS  PubMed  Google Scholar 

  28. Ren S-M, Zhang C-X, Li W-C (2010) Expression of T-bet and GATA3 in children with acute thrombocytopenic purpura. Chin J Contemp Pediatr 12(1):29–31

    CAS  Google Scholar 

  29. Kawashima M, Miossec P (2005) Effect of treatment of rheumatoid arthritis with infliximab on IFNγ, IL4, T-bet, and GATA-3expression: link with improvement of systemic inflammation and disease activity. Ann Rheum Dis 64:415–418

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank professor dr. Seham Omar for her continuous guidance and support

Author information

Authors and Affiliations

  1. Clinical Pathology Department, Faculty of Medicine, Beni Suef University, Beni Suef, Egypt

    Amira Ahmed Hammam & Marwa Hamed Abd Elwahab

  2. Pediatrics Department, Faculty of Medicine, Beni Suef University, Beni Suef, Egypt

    Amira Ahmed Hammam, Dina Ahmed Ezzat & Marwa Hamed Abd Elwahab

  3. Clinical Pathology Department, Ministry of Health Hospitals, Giza, Egypt

    Dina Ahmed Ezzat

Authors
  1. Amira Ahmed Hammam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dina Ahmed Ezzat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marwa Hamed Abd Elwahab
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amira Ahmed Hammam.

Ethics declarations

Conflict of interest

No conflicts of interest to be declared.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hammam, A.A., Ezzat, D.A. & Elwahab, M.H.A. Differential Expression of T-bet and GATA3 in Egyptian Children with Idiopathic Thrombocytopenic Purpura. Indian J Hematol Blood Transfus 32, 460–467 (2016). https://doi.org/10.1007/s12288-015-0625-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12288-015-0625-z

Keywords

Search

Navigation