Immune Cell Subsets Evaluation as a Predictive Tool for Hepatitis B Infection Outcome and Treatment Responsiveness

Snezhina M. Kandilarova 1 , Atanaska I. Georgieva 1 , Anastasiya P. Mihaylova 1 , Marta P. Baleva 2 , Valentina K. Atanasova 1 , Diana V. Petrova 3 , Georgi T. Popov 4  and Elissaveta J. Naumova 5
  • 1 Department of Clinical Immunology and Stem Cell Bank, Alexandrovska University Hospital, Medical University of Sofia, 1 G. Sofiisky St. 1431 Sofia, Bulgaria
  • 2 Department of Clinical Immunology and Stem Cell Bank, Alexandrovska University Hospital, Medical University of Sofia, Sofia, Bulgaria
  • 3 Clinic of Propaedeutics of Internal Diseases, Alexandrovska University Hospital, Medical University of Sofia, Sofia, Bulgaria
  • 4 Clinic of Infectious Diseases, Military Medical Academy, Sofia, Bulgaria
  • 5 Department of Clinical Immunology and Stem Cell Bank, Alexandrovska University Hospital, Medical University of Sofia, 1 G. Sofi isky St. 1431 Sofia, Bulgaria

Abstract

Background: The patient’s immune response is one of the major factors influencing HBV eradication or chronification, and it is thought to be responsible for the treatment success.

Aim: Our study aimed to investigate whether cellular defense mechanisms are associated with the course of HBV infection (spontaneous recovery [SR] or chronification [CHB]) and with the therapeutic approach.

Patients and methods: A total of 139 patients (118 with CHB, 21 SR) and 29 healthy individuals (HI) were immunophenotyped by flowcytometry. Fifty-six patients were treatment-naïve, 20 were treated with interferons and 42 with nucleoside/ nucleotide analogues.

Results: Deficiency of T lymphocytes, helper-inducer (CD3+CD4+), suppressorcytotoxic (CD8+CD3+) and cytotoxic (CD8+CD11b-, CD8+CD28+) subsets, activated T cells (CD3+HLA-DR+, CD8+CD38+) and increased CD57+CD8- cells, elevated percentages of B lymphocytes and NKT cells were observed in CHB patients compared with HI. In SR patients, elevated CD8+CD11b+, NKT and activated T cells were found in comparison with controls. The higher values of T cells and their subsets in SR patients than in CHB patients reflect a recovery of cellular immunity in resolved HBV infection individuals. In both groups of treated patients, reduced T lymphocytes, CD3+CD4+ and CD8+CD38+ subsets were found in comparison with HI. Higher proportions of cytotoxic subsets were observed in treated patients compared with treatment-naïve CHB patients, more pronounced in the group with interferon therapy.

Conclusion: Our data demonstrate that cellular immune profiles may be of prognostic value in predicting the clinical course of HBV infection, and the determination of the therapeutic response.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. World Health Organization. Hepatitis B. Updated July 2015, World Health Organization Fact Sheet №204. Available from: http://www.who.int/mediacentre/factsheets/fs204/en.

  • 2. Schweitzer A, Horn J, Mikolajczyk RT, et al. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet 2015;386 (10003):1546-55.

  • 3. Chisari FV, Isogawa M, Wieland SF. Pathogenesis of hepatitis B virus infection. Pathologie Biologie 2010;58(4):258-66.

  • 4. Landay A, Gartland GL, Clement LT. Characterization of a phenotypically distinct subpopulation of Leu-2+ cells that suppresses T cell proliferative responses. J Immunol 1983;131(6):2757-61.

  • 5. Clement LT, Dagg MK, Landay A. Characterization of human lymphocyte subpopulations: alloreactive cytotoxic T-lymphocyte precursor and effector cells are phenotypically distinct from Leu 2+ suppressor cells. J Clin Immunol 1984;4(5):395-402.

  • 6. Arosa FA. CD8+CD28- T cells: certainties and uncertainties of a prevalent human T-cell subset. Immunol Cell Biol 2002;80(1):1-13.

  • 7. Strioga M, Pasukoniene V, Characiejus D. CD8+ CD28- and CD8+ CD57+ T cells and their role in health and disease. Immunology 2011;134(1):17-32.

  • 8. Coppo P, Buffet M, Féger F, et al. Polyclonal CD8+/ CD57+ T cell expansions: clinical signifi cance. Presse Med 2013;42(3):327-37.

  • 9. Nielsen CM, White MJ, Goodier MR, et al. Functional signifi cance of CD57 expression on human NK cells and relevance to disease. Front Immunol 2013;4:422.

  • 10. Mehta K, Shahid U, Malavasi F. Human CD38, a cell-surface protein with multiple functions. FASEB J 1996;10(12):1408-17.

  • 11. Bertoletti A, Gehring AJ. The immune response during hepatitis B virus infection. Journal of General Virology 2006;87(Pt6):1439-49.

  • 12. You J, Sriplung H, Geater A, et al. Hepatitis B virus DNA is more powerful than HBeAg in predicting peripheral T-lymphocyte subpopulations in chronic HBV-infected individuals with normal liver function tests. World J Gastroenterol 2008;14(23):3710-8.

  • 13. You J, Zhuang L, Zhang YF, et al. Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load. World J Gastroenterol 2009;15(27):3382-93.

  • 14. Xibing G, Xiaojuan Y, Zhonghua L, et al. Alteration in cellular immunity after chronic hepatitis B deteriorated into severe hepatitis and its significance. Hepat Mon 2011;11(10):810-5.

  • 15. Boni C, Penna A, Ogg GS, et al. Lamivudine treatment can overcome cytotoxic T-cell hyporesponsiveness in chronic hepatitis B: new perspectives for immune therapy. Hepatology 2001;33(4):963-71.

  • 16. Mukherjee RM, Reddy PB, Arava J, et al. Relationship between serum HBsAg level, HBV DNA level, and peripheral immune cells in patients with chronic hepatitis B virus infection. Hepatic Medicine: Evidence and Research 2010;2:157-62.

  • 17. Sun H, Lv J, Tu Z, et al. Antiviral treatment improves disrupted peripheral B lymphocyte homeostasis in chronic hepatitis B virus-infected patients. Exp Biol Med 2013;238(11):1275-83.

  • 18. Zhao PW, Jia FY, Shan YX, et al. Downregulation and altered function of natural killer cells in hepatitis B virus patients treated with entecavir. Clin Exp Pharmacol Physiol 2013;40(3):190-6.

  • 19. Li Y, Wang JJ, Gao S, et al. Decreased peripheral natural killer cells activity in the immune activated stage of chronic hepatitis B. PLoS One 2014;9 2):e86927. doi:

    • Crossref
    • Export Citation
  • 20. Cao W, Qiu ZF, Li TS. Parallel decline of CD8+CD38+ lymphocytes and viremia in treated hepatitis B patients. World J Gastroenterol 2011;17(17):2191-8.

  • 21. Li X, Kong H, Tian L, et al. Changes of costimulatory molecule CD28 on circulating CD8+ T cells correlate with disease pathogenesis of chronic hepatitis B. Biomed Res Int 2014(5):423181. doi:

    • Crossref
    • Export Citation
  • 22. You J, Zhuang L, Zhang YF, et al. Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load. World J Gastroenterol 2009;15(27):3382-93.

  • 23. Yu HB, Ma LN, Liu YL, et al. Changes in lymphocyte surface expression of CD8 and CD38 molecules in peripheral blood of inactive HBsAg carriers following pegylated interferon a-2a therapy. Zhonghua Gan Zang Bing Za Zhi 2013;21(12):895-8.

  • 24. Boni C, Penna A, Bertoletti A, et al. Transient restoration of anti-viral T cell responses induced by lamivudine therapy in chronic hepatitis B. J Hepatol 2003;39(4)595-605.

OPEN ACCESS

Journal + Issues

Search