Skip to main content

Advertisement

Log in

Telomerase Activity Increased and Telomere Length Shortened in Peripheral Blood Cells from Patients with Immune Thrombocytopenia

  • Original Research
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Objectives

To evaluate the telomere/telomerase system and its clinical significance in immune thrombocytopenia (ITP) patients.

Methods

A total of 237 ITP patients, 20 SLE patients and 200 age-and sex-matched healthy controls were included in this study. CD4+, CD8+ and CD19+ lymphocytes were purified by magnetic beads sorting from peripheral blood of 37 active chronic ITP patients and 22 age-and sex-matched healthy controls. Telomerase activity was assayed by Telo TTAGGG Telomerase PCR ELISA KIT. The relative telomere length of peripheral blood mononuclear cell (PBMC) was measured by a quantitative polymerase chain reaction-based method (Q-PCR) from 200 ITP patients and 178 age-and sex-matched healthy controls.

Results

Telomerase activity was increased in CD4+, CD8+ and CD19+ lymphocytes from ITP patients compared to those from healthy controls (p = 0.000). The level of telomerase activity in CD19+ lymphocyte was higher than those in CD4+ and CD8+ lymphocytes. Telomerase activity of CD19+ lymphocytes had a modest negative correlation with platelet count in ITP patients (p = 0.042). The relative telomere length of PBMC in ITP patients was significantly shorter than that in the healthy controls (p = 0.002). Telomere length of PBMC in active ITP patients was significantly shorter than that in the controls (p = 0.000) and a tendency to be shorter even in inactive ITP patients (p = 0.065). Moreover, the telomere length in refractory and non-refractory ITP patients were both significantly shorter than that in the controls (p = 0.025; p = 0.000). However no significant difference in telomere length of PBMC was found between refractory ITP patients and non-refractory ITP patients (p = 0.234).

Conclusion

An abnormal regulating telomere/telomerase system might be involved in the pathogenesis of ITP. Further studies may elucidate whether the telomere length could be considered as a predictive biomarker for the prognosis of ITP.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kuhne T, Ruggeri M, George JN. 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  PubMed  CAS  Google Scholar 

  2. Semple JW, Provan D, Garvey MB, Freedman J. Recent progress in understanding the pathogenesis of immune thrombocytopenia. Curr Opin Hematol. 2010;17:590–5.

    Article  PubMed  CAS  Google Scholar 

  3. Aubert G, Lansdorp PM. Telomeres and aging. Physiol Rev. 2008;88:557–79.

    Article  PubMed  CAS  Google Scholar 

  4. Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet. 2008;42:301–34.

    Article  PubMed  CAS  Google Scholar 

  5. Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci USA. 2004;101:17312–5.

    Article  PubMed  CAS  Google Scholar 

  6. Njajou OT, Cawthon RM, Damcott CM, Wu SH, Ott S, Garant MJ, Blackburn EH, Mitchell BD, Shuldiner AR, Hsueh WC. Telomere length is paternally inherited and is associated with parental lifespan. Proc Natl Acad Sci U S A. 2007;104:12135–9.

    Article  PubMed  CAS  Google Scholar 

  7. Kimura M, Cherkas LF, Kato BS, Demissie S, Hjelmborg JB, Brimacombe M, Cupples A, Hunkin JL, Gardner JP, Lu X, Cao X, Sastrasinh M, Province MA, Hunt SC, Christensen K, Levy D, Spector TD, Aviv A. Offspring’s leukocyte telomere length, paternal age, and telomere elongation in sperm. PLoS Genet. 2008;4:e37.

    Article  PubMed  Google Scholar 

  8. Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med. 2005;352:1413–24.

    Article  PubMed  CAS  Google Scholar 

  9. Savage SA, Bertuch AA. The genetics and clinical manifestations of telomere biology disorders. Genet Med. 2010;12:753–64.

    Article  PubMed  Google Scholar 

  10. Blackburn EH. Telomeres and telomerase: Their mechanisms of action and the effects of altering their functions. FEBS Lett. 2005;579:859–62.

    Article  PubMed  CAS  Google Scholar 

  11. Masutomi K, Yu EY, Khurts S, Ben-Porath I, Currier JL, Metz GB, Brooks MW, Kaneko S, Murakami S, DeCaprio JA, Weinberg RA, Stewart SA, Hahn WC. Telomerase maintains telomere structure in normal human cells. Cell. 2003;114:241–53.

    Article  PubMed  CAS  Google Scholar 

  12. Georgin-Lavialle S, Aouba A, Mouthon L, Londono-Vallejo JA, Lepelletier Y, Gabet AS, Hermine O. The telomere/telomerase system in autoimmune and systemic immune-mediated diseases. Autoimmun Rev. 2010;9:646–51.

    Article  PubMed  CAS  Google Scholar 

  13. Goronzy JJ, Fujii H, Weyand CM. Telomeres, immune aging and autoimmunity. Exp Gerontol. 2006;41:246–51.

    Article  PubMed  CAS  Google Scholar 

  14. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25:1271–7.

    Article  PubMed  CAS  Google Scholar 

  15. Page LK, Psaila B, Provan D, Michael Hamilton J, Jenkins JM, Elish AS, Lesser ML, Bussel JB. The immune thrombocytopenic purpura (ITP) bleeding score: Assessment of bleeding in patients with ITP. Br J Haematol. 2007;138:245–8.

    Article  PubMed  Google Scholar 

  16. Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002;30:e47.

    Article  PubMed  Google Scholar 

  17. Yang Z, Huang X, Jiang H, Zhang Y, Liu H, Qin C, Eisner GM, Jose PA, Rudolph LJZ. Short telomeres and prognosis of hypertension in a chinese population. Hypertension. 2009;53:639–45.

    Article  PubMed  CAS  Google Scholar 

  18. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266:2011–5.

    Article  PubMed  CAS  Google Scholar 

  19. Hathcock KS, Jeffrey Chiang Y, Hodes RJ. In vivo regulation of telomerase activity and telomere length. Immunol Rev. 2005;205:104–13.

    Article  PubMed  CAS  Google Scholar 

  20. Klapper W, Moosig F, Sotnikova A, Qian W, Schroder JO, Parwaresch R. Telomerase activity in B and T lymphocytes of patients with systemic lupus erythematosus. Ann Rheum Dis. 2004;63:1681–3.

    Article  PubMed  CAS  Google Scholar 

  21. Son NH, Murray S, Yanovski J, Hodes RJ, Weng N. Lineage-specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age. J Immunol. 2000;165:1191–6.

    PubMed  CAS  Google Scholar 

  22. Kurosaka D, Yasuda J, Yoshida K, Yokoyama T, Ozawa Y, Obayashi Y, Kingetsu I, Saito S, Yamada A. Telomerase activity and telomere length of peripheral blood mononuclear cells in SLE patients. Lupus. 2003;12:591–9.

    Article  PubMed  CAS  Google Scholar 

  23. Weng NP, Granger L, Hodes RJ. Telomere lengthening and telomerase activation during human B cell differentiation. Proc Natl Acad Sci U S A. 1997;94:10827–32.

    Article  PubMed  CAS  Google Scholar 

  24. Shimomura T, Fujimura K, Takafuta T, Fujii T, Katsutani S, Noda M, Fujimoto T, Kuramoto A. Oligoclonal accumulation of T cells in peripheral blood from patients with idiopathic thrombocytopenic purpura. Br J Haematol. 1996;95:732–7.

    Article  PubMed  CAS  Google Scholar 

  25. van der Harst D, de Jong D, Limpens J, Kluin PM, Rozier Y, van Ommen GJ, Brand A. Clonal B-cell populations in patients with idiopathic thrombocytopenic purpura. Blood. 1990;76:2321–6.

    PubMed  Google Scholar 

  26. Beier F, Balabanov S, Amberger CC, Hartmann U, Manger K, Dietz K, Kotter I, Brummendorf TH. Telomere length analysis in monocytes and lymphocytes from patients with systemic lupus erythematosus using multi-color flow-FISH. Lupus. 2007;16:955–62.

    Article  PubMed  CAS  Google Scholar 

  27. Fritsch RD, Shen X, Illei GG, Yarboro CH, Prussin C, Hathcock KS, Hodes RJ, Lipsky PE. Abnormal differentiation of memory T cells in systemic lupus erythematosus. Arthritis Rheum. 2006;54:2184–97.

    Article  PubMed  CAS  Google Scholar 

  28. Kurosaka D, Yasuda J, Yoshida K, Yoneda A, Yasuda C, Kingetsu I, Toyokawa Y, Yokoyama T, Saito S, Yamada A. Abnormal telomerase activity and telomere length in T and B cells from patients with systemic lupus erythematosus. J Rheumatol. 2006;33:1102–7.

    PubMed  CAS  Google Scholar 

  29. Honda M, Mengesha E, Albano S, Nichols WS, Wallace DJ, Metzger A, Klinenberg JR, Linker-Israeli M. Telomere shortening and decreased replicative potential, contrasted by continued proliferation of telomerase-positive CD8+CD28(lo) T cells in patients with systemic lupus erythematosus. Clin Immunol. 2001;99:211–21.

    Article  PubMed  CAS  Google Scholar 

  30. Damjanovic AK, Yang Y, Glaser R, Kiecolt-Glaser JK, Nguyen H, Laskowski B, Zou Y, Beversdorf DQ, Weng NP. Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer’s disease patients. J Immunol. 2007;179:4249–54.

    PubMed  CAS  Google Scholar 

  31. Calado RT. Telomeres and marrow failure. Hematology Am Soc Hematol Educ Program. 2009: 338–343.

  32. Bisoffi M, Heaphy CM, Griffith JK. Telomeres: prognostic markers for solid tumors. Int J Cancer. 2006;119:2255–60.

    Article  PubMed  CAS  Google Scholar 

  33. Lin KW, Yan J. The telomere length dynamic and methods of its assessment. J Cell Mol Med. 2005;9:977–89.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants of National Natural Science Foundation of China (81070397, 81170474), Ministry of Science and Technology (2011ZX09302-007-04), Ministry of Health (201202017) and Tianjin Municipal Science and Technology Commission (09JCYBJC10900, 10JCZDJC19700). The authors would like to thank Prof. Man-Chiu Poon (University of Calgary, Canada) for critical review of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Renchi Yang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Qi, A., Zhou, H., Zhou, Z. et al. Telomerase Activity Increased and Telomere Length Shortened in Peripheral Blood Cells from Patients with Immune Thrombocytopenia. J Clin Immunol 33, 577–585 (2013). https://doi.org/10.1007/s10875-012-9848-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-012-9848-z

Keywords

Navigation