Subpopulation composition of blood NK cells in patients with hepatitis C with genotype 1 or 3
V. V. Tsukanov,
M. A. Cherepnin,
A. A. Savchenko,
A. V. Vasyutin,
E. V. Kasparov,
A. G. Borisov,
V. D. Belenyuk,
Ju. L. Tonkikh https://doi.org/10.21518/ms2023-058
Abstract
Introduction. Recently, there has been increased interest in the role of NK cells in viral hepatitis. An antifibrotic effect of these cells has been found, but the causes of their dysfunction leading to the development of liver fibrosis remain unclear.
Aim. To study the subpopulation composition of blood NK cells by flow cytometry, depending on the severity of clinical and morphological manifestations of chronic viral hepatitis C (CVHC) with genotype 1 or 3.
Materials and methods. Clinical, laboratory examinations, determination of liver fibrosis by elastometry using the METAVIR scale and study of the subpopulation composition of NK cells in the blood by flow cytometry (with definition of markers CD3, CD16 and CD56) were carried out in 143 patients with CVHC, including 74 patients with genotype 1 and 69 individuals with genotype 3, and in 20 people of the control group.
Results. In patients with both CVHC genotypes 1 and 3, a significant decrease in the total content of NK cells, CD3-CD16+CD56bright and CD3-CD16+CD56dim subpopulations in the blood among individuals with liver fibrosis F3-F4 according to METAVIR was registered in comparison with patients with liver fibrosis F0-F1 according to METAVIR. In patients with CVHC genotype 3, there was a decrease in the total content of NK cells and a subpopulation of CD3-CD16+CD56dim in the blood of individuals with a high viral load compared to patients with a low viral load. This relationship was not determined in patients with CVHC genotype 1.
Conclusion. The obtained regularities emphasize the significant role of NK cells in the pathogenesis of CVHC and verify the idea of using NK cells activation for immunotherapy of liver fibrosis in patients with CVHC.
About the Authors
V. V. Tsukanov
Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Vladislav V.Tsukanov - Dr. Sci. (Med.), Professor, Head of the Clinical Department of the Digestive System Pathology of Adults and Children of Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”.
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
M. A. Cherepnin
Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Mikhail A. Cherepnin - Junior Researcher of the Clinical Department of the Digestive System Pathology of Adults and Children of Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”.
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
A. A. Savchenko
Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Andrei A. Savchenko - Dr. Sci. (Med.), Professor, Head of the Laboratory of Cellular and Molecular Physiology and Pathology of Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”.
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
A. V. Vasyutin
Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Alexander V. Vasyutin - Cand. Sci. (Med.), Senior Researcher of the Clinical Department of the Digestive System Pathology of Adults and Children of Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”.
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
E. V. Kasparov
Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Eduard V. Kasparov - Dr. Sci. (Med.), Professor, Director of the Scientific Research Institute of medical problems of the North, Deputy Director for Scientific and Organizational Work of Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”.
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
A. G. Borisov
Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Alexander G. Borisov - Cand. Sci. (Med.), Leading Researcher of the Laboratory of Cellular and Molecular Physiology and Pathology of Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”.
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
V. D. Belenyuk
Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Vasilij D. Belenyuk - Cand. Sci. (Med.), Junior Researcher of the Laboratory of Cellular and Molecular Physiology and Pathology of Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”.
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
Ju. L. Tonkikh
Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Julia L. Tonkikh - Cand. Sci. (Med.), Leading Researcher of the Clinical Department of the Digestive System Pathology of Adults and Children of Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”.
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
References
1. Njiomegnie GF, Read SA, Fewings N, George J, McKay F, Ahlenstiel G. Immunomodulation of the Natural Killer Cell Phenotype and Response during HCV Infection. J Clin Med. 2020;9(4):1030. https://doi.org/10.3390/jcm9041030.
2. Herberman RB, Nunn ME, Lavrin DH. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer. 1975;16(2):216–229. https://doi.org/10.1002/ijc.2910160204.
3. Kiessling R, Klein E, Wigzell H. “Natural” killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol. 1975;5(2):112–117. https://doi.org/10.1002/eji.1830050208.
4. Goyos A, Fort M, Sharma A, Lebrec H. Current Concepts in Natural Killer Cell Biology and Application to Drug Safety Assessments. Toxicol Sci. 2019;170(1):10–19. https://doi.org/10.1093/toxsci/kfz098.
5. Mandal A, Viswanathan C. Natural killer cells: In health and disease. Hematol Oncol Stem Cell Ther. 2015;8(2):47–55. https://doi.org/10.1016/j.hemonc.2014.11.006.
6. Howell J, Visvanathan K. The role of natural killer cells in hepatitis C infection. Antivir Ther. 2013;18(7):853–865. https://doi.org/10.3851/IMP2565.
7. Björkström NK, Strunz B, Ljunggren HG. Natural killer cells in antiviral immunity. Nat Rev Immunol. 2022;22(2):112–123. https://doi.org/10.1038/s41577-021-00558-3.
8. Mele D, Oliviero B, Mantovani S, Ludovisi S, Lombardi A, Genco F et al. Adaptive Natural Killer Cell Functional Recovery in Hepatitis C Virus Cured Patients. Hepatology. 2021;73(1):79–90. https://doi.org/10.1002/hep.31273.
9. Wei Y, Bingyu W, Lei Y, Xingxing Y. The antifibrotic role of natural killer cells in liver fibrosis. Exp Biol Med (Maywood). 2022;247(14):1235–1243. https://doi.org/10.1177/15353702221092672.
10. Yoon JC, Yang CM, Song Y, Lee JM. Natural killer cells in hepatitis C: Current progress. World J Gastroenterol. 2016;22(4):1449–1460. https://doi.org/10.3748/wjg.v22.i4.1449.
11. European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatol. 2017;66(1):153–194. https://doi.org/10.1016/j.jhep.2016.09.001.
12. European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2018. J Hepatol. 2018;69(2):461–511. https://doi.org/10.1016/j.jhep.2018.03.026.
13. Ludwig J. Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. Am J Gastroenterol. 1994;89(8 Suppl.):177–181. Available at: https://pubmed.ncbi.nlm.nih.gov/8048409.
14. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997;349(9055):825–832. https://doi.org/10.1016/s0140-6736(96)07642-8.
15. Kudryavtsev IV, Subbotovskaya AI. Application of six-color flow cytometric analysis for immune profile monitoring. Medical Immunology (Russia). 2015;17(1):19–26. (In Russ.) Available at: https://www.mimmun.ru/mimmun/article/viewFile/803/747.
16. Sutherland DR, Ortiz F, Quest G, Illingworth A, Benko M, Nayyar R, Marinov I. High-sensitivity 5-, 6-, and 7-color PNH WBC assays for both Canto II and Navios platforms. Cytometry B Clin Cytom. 2018;94(4):637–651. https://doi.org/10.1002/cyto.b.21626.
17. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22(11):633–640. https://doi.org/10.1016/s1471-4906(01)02060-9.
18. Caligiuri MA. Human natural killer cells. Blood. 2008;112(3):461–469. https://doi.org/10.1182/blood-2007-09-077438.
19. Poli A, Michel T, Thérésine M, Andrès E, Hentges F, Zimmer J. CD56bright natural killer (NK) cells: an important NK cell subset. Immunology. 2009;126(4):458–465. https://doi.org/10.1111/j.1365-2567.2008.03027.x.
20. Yan Y, Zeng J, Xing L, Li C. Extra- and Intra-Cellular Mechanisms of Hepatic Stellate Cell Activation. Biomedicines. 2021;9(8):1014. https://doi.org/10.3390/biomedicines9081014.
21. Zhang Y, Wu Y, Shen W, Wang B, Yuan X. Crosstalk between NK cells and hepatic stellate cells in liver fibrosis (Review). Mol Med Rep. 2022;25(6):208. https://doi.org/10.3892/mmr.2022.12724.
22. Spengler U, Nattermann J. Immunopathogenesis in hepatitis C virus cirrhosis. Clinical Science. 2007;112(3):141–155. https://doi.org/10.1042/CS20060171.
23. Gao B, Radaeva S, Jeong WI. Activation of natural killer cells inhibits liver fibrosis: a novel strategy to treat liver fibrosis. Expert Rev Gastroenterol Hepatol. 2007;1(1):173–180. https://doi.org/10.1586/17474124.1.1.173.
24. Tian Z, Chen Y, Gao B. Natural killer cells in liver disease. Hepatology. 2013;57(4):1654–1662. https://doi.org/10.1002/hep.26115.
25. Cheent K, Khakoo SI. Natural killer cells and hepatitis C: action and reaction. Gut. 2011;60(2):268–278. https://doi.org/10.1136/gut.2010.212555.
26. Ahlenstiel G, Titerence RH, Koh C, Edlich B, Feld JJ, Rotman Y et al. Natural killer cells are polarized toward cytotoxicity in chronic hepatitis C in an interferon-alfa-dependent manner. Gastroenterology. 2010;138(1):325–335.e1-e2. https://doi.org/10.1053/j.gastro.2009.08.066.
27. Edlich B, Ahlenstiel G, Zabaleta Azpiroz A, Stoltzfus J, Noureddin M, Serti E et al. Early changes in interferon signaling define natural killer cell response and refractoriness to interferon-based therapy of hepatitis C patients. Hepatology. 2012;55(1):39–48. https://doi.org/10.1002/hep.24628.
28. Cherepnin MA, Tsukanov VV, Savchenko AA, Vasyutin AV, Tonkikh JL, Borisov AG. Clinical manifestations in patients with genotypes 1 and 3 of viral hepatitis “C”, depending on the severity of liver fibrosis. Doctor.Ru. 2023;22(2):32–38. (In Russ.) https://doi.org/10.31550/1727-2378-2023-22-2-32-38.
29. Cherepnin MA, Tsukanov VV, Savchenko AA, Vasyutin AV, Kasparov EV, Tonkikh JL, Borisov AG. Comparison of clinical and laboratory characteristics and frequency of liver fibrosis in patients with chronic viral hepatitis C of the first and third genotypes. Meditsinskiy Sovet. 2022;(7):98–103. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-7-98-103.
Review
For citations:
Tsukanov VV, Cherepnin MA, Savchenko AA, Vasyutin AV, Kasparov EV, Borisov AG, Belenyuk VD, Tonkikh JL. Subpopulation composition of blood NK cells in patients with hepatitis C with genotype 1 or 3. Meditsinskiy sovet = Medical Council. 2023;(18):44-51. (In Russ.) https://doi.org/10.21518/ms2023-058
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