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DOI: https://doi.org/10.22263/2312-4156.2017.1.50

Usychenko E.N., Usychenko E.M., Bazhora Y.I.
Immune status and gene polymorphism of cytokines IL-10, IL-4, TNF in patients with chronic hepatitis C depending on the degree of fibrosis
Odessa National Medical University, Odessa, Ukraine

Vestnik VGMU. 2017;16(1):50-58.

Abstract.
Objectives. To study gene polymorphisms of IL-10 (G1082A), IL-4 (C589T) and TNF  (G308A) and cellular immunity indices (CD3+, CD4+, CD8+, CD16+, CD19+) in patients with chronic hepatitis C (CHC) and healthy persons belonging to the ethnically homogeneous group of the Odessa region residents, as well as to identify possible association of certain genotypes and the degree of liver fibrosis.
Material and methods. The study included 100 patients with CHC. The control group consisted of 30 people having no diseases of the hepatobiliary system. Traditional diagnostic methods stipulated by the protocol in effect were used. Polymorphism was studied using  amplification of the corresponding regions of the genome by PCR method. The structure of the primers used was described in the data base GenBank. The evaluation of morphological changes in the liver (the degree of activity and the severity of fibrotic changes) was made according to METAVIR scale using a noninvasive method Fibrotest.
Results. A certain level of statistical significance of certain genotypes of cytokines, cellular immunity indices and the degree of liver fibrosis was established. Patients with the homozygous CC genotype IL-4 had smaller fibrotic changes in the liver compared to the carriers of the homozygous TT genotype (p<0,01).
Patients with the homozygous genotype GG TNFPPhad a lower degree of liver fibrosis in comparison with the carriers of the homozygous genotype AA (p<0,01). Patients with smaller changes in cellular immunity indices (reduction of CD3+, CD4+, CD16+, CD19+) had a lower degree of liver fibrosis (p<0,01). Patients with higher levels of CD8 + had a higher degree of liver fibrosis (p<0,01).
Conclusions. The presence of an interconnection between the degree of liver fibrosis and certain genotypes of IL-4 and TNF  allows to use the received information as a criterion of the progression speed of fibrotic processes in the liver. The expressiveness of the changes in cellular immunity indices is an additional criterion of the degree of morphological disturbances in the liver tissue.
Key words: chronic hepatitis C, gene polymorphism, liver fibrosis, cell-mediated immunity.

References

1. Ivashkin VT. Mechanisms of immune tolerance and pathology of a liver. Ros Zhurn Gastroenterologii Gepatologii Koloproktologii. 2009;19(2):8-13. (In Russ.)
2. Maev IV, Polunina TE, Polunina EV. A chronic viral hepatitis With - an etiology, a pathogenesis, treatment. Klin Meditsina. 2009;87(11):12-7. (In Russ.)
3. Lobzin YuV, Nikitin VYu, Mitin YuA, Sukhina IA, Tsygan VN. Immunopathogenesis of viral hepatitis C. Immunological markers of disease progression. Zhurn Mikrobiologii. 2007:(6):75-84. (In Russ.)
4. Ivashkin VT. Immune system and injuries of a liver at chronic hepatitises B and C. Ros Zhurn Gastroenterologii Gepatologii Koloproktologii. 2009;19(6):4-10. (In Russ.)
5. Schildberg FA, Hegenbarth SI, Schumak B, Scholz K, Limmer A, Knolle PA. Liver sinusoidal endothelial cells veto CD8T cell activation by antigen – presenting dendritic cell. Eur J Immunol. 2008 Apr;38(4):957-67. doi: 10.1002/eji.200738060.
6. Lazareva AS, Volchkova EV, Umbetova KT, Chulanov VP, Parkhomenko YuG, Kiselevskiy MV, i dr. Features of a tsitokinovy profile and subpopulation structure of lymphocytes of a peripheric blood at patients with a chronic viral hepatitis In and With in comparison to expression of morphological changes of a liver. Terapevt Arkhiv. 2009;81(4):55-60. (In Russ.)
7. Sepiashvili RI, Balmasova IP. Physiology of natural killers. Moscow, RF: Meditsina-Zdorov'e; 2005. 456 р. (In Russ.)
8. Oliviero B, Varchetta S, Paudice E, Michelone G, Zaramella M, Mavilio D, et al. Gastroenterology. 2009 Sep;137(3):1151-60, 1160.e1-7. doi: http://dx.doi.org/10.1053/j.gastro.2009.05.047
9. Balmasova IP, Yushchuk ND, Znoyko OO, Shmeleva EV, Dunda NI, Eremina OF, i dr. Ratio of subpopulations of EK/EKT as prognostic criterion of chronic hepatitis C. Allergologiia Immunologiia. 2009;10(3):340-3. (In Russ.)
10. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008 Jan; 214(2): 199–210. doi: http://dx.doi.org/10.1002/path.2277
11. Malova ES, Yushchuk ND, Balmasova IP, Shmeleva EV. CD56 + lymphocytes and immunopathogenesis of chronic hepatitis C. Immunologiia. 2010;31(6):310-4. (In Russ.)
12. Morozova TS, Grishina IF, Postnikova TN, Gurikova IA. Assessment of subpopulation structure of lymphocytes of a peripheric blood at the chronic diffuse diseases of a liver associated with a HCV infection. Allergologiia Immunologiia. 2014;15(1):70. (In Russ.)
13. Sobchak DM, Korochkina OV. Assessment of indicators of a reactivity of immune system at patients with chronic hepatitis C. Terapevt Arkhiv. 2008;80(2):61-6. (In Russ.)
14. Nikolaeva LI, Kolotvin AV, Samokhodskaya LM, Sapronov GV, Makashova VV, Samokhvalov EI, i dr. The analysis of influence of genetic factors of a virus of hepatitis C and a polymorphism of genes of the infected people on development of a fibrosis of a liver. Epidemiologiia Infekts Bolezni. 2012;(5):7-13. (In Russ.)
15. Tikhonova NYu, Burnevich EZ, Krasnova TN. Value of allelic options of a gene interleykina-28B at a chronic viral hepatitis C. Terapevt Arkhiv. 2013;85(12):106-13. (In Russ.)
16. Yushchuk ND, Znoyko OO, Balmasova IP, Fedoseeva NV, Shmeleva EV, Dudina KR, i dr. Immunogenetic predictors of the prompt virologic reply to antiviral therapy of patients with chronic hepatitis C. Terapevt Arkhiv. 2012;84(11):11-6. (In Russ.)
17. Ketlinskiy SA, Simbirtsev AS. Cytokines. Saint Petersburg, RF: Foliant; 2008. 552 р. (In Russ.)
18. Sergeev IV, Khaitov MR, Trofimov DYu, Abramov DD, Grudakova EG, Goncharova EV, i dr. Development of methods for carrying out large-scale researches of a polymorphism of the genes regulating various components of an immune response. Fiziologiia Patologiia Immun Sistemy. 2009;13(4):21-6. (In Russ.)
19. Zhou L,Wang H, Zhong X, Jin Y, Mi QS, Sharma A, et al. The IL-10 and IFN-gamma pathways are essential to the potent immunosuppressive activity of cultered CD8+ NKT-like cells. Genome Biol. 2008;9(7):R119. doi: http://dx.doi.org/10.1186/gb-2008-9-7-r119
20. Goncharova IA, Gamal'Abd El'-Aziz Nasr X, Beloborodova EV, Ozhegova DS, Stepanov VA, Puzyrev VP. A polymorphism of genes - modifiers of an immune response at diseases of a liver of various etiology. Med Genetika. 2010;9(12):20-4. (In Russ.)
21. Rau M, Weisskopf M, Stickel F, Geier A. Impact of genetic concentrative nucleoside transporter variants on peg-interferon/ribavirin therapy response and ribavirin serum levels in Hepatitis C patients. J Hepatol. 2012 Apr;56:S455-6. doi: http://dx.doi.org/10.1016/S0168-8278
22. Rao HY, Sun DG, Jiang D, Yang RF, Guo F, Wang JH, et al. Il28b genetic variants and gender are associated with spontaneous clearance of Hepatitis C virus infection. J Viral Hepat. 2012 Mar;19(3):173-81. doi: http://dx.doi.org/10.1111/j.1365-2893.2011.01497.x
23. Mustafina OE, Timasheva YaR, Tulyakova GKh, Nasibullin TR, Tuktarova IA, Pauk VV, i dr. Polymorphism -627С>A interleukin-10 gene: analysis of Association with cardiovascular disease. Med Genetika. 2010;9(5):12-7.
24. Abramov DD, Kofiad IA, Utkin KV, Trofimov DYu, Khaitov RM, Alekseev LP. A single nucleotide polymorphism in the genes of cytokines and their receptors: biological effects and methods of identification. Immunologiia. 2011;(5):275-80. (In Russ.)
25. Afzal MS, Tahir S, Salman A, Baig TA, Shafi T, Zaidi NU, et al. Analysis of interleukin-10 gene polymorphisms and hepatitis C susceptibility in Pakistan. J Infect Dev Ctries. 2011 Jul;5(6):473-9.
26. Goncharova IA, Beloborodova EV, Freydin MB, Beloborodova EI, Chernogoryuk GE, Puzyrev VP. Genetic factors in the susceptibility to chronic viral hepatitis and liver fibrosis. Molekuliar Biologiia. 2008;42(2):238-41. (In Russ.)
27. Khaitov RM, Yarilin AA, Pinegin BV. Immunology: atlas. Moscow, RF:
 GEOTAR-Media; 2011. 624 р. (In Russ.)
28. Lee D, Chung Y-H, Kim JA, Kim SE, Choi J-K, Yoo D-J. et al. Tumor necrosis factor-alpha promoter gene polymorphism affects the occurrence of hepatocellular carcinoma in patients with chronic hepatitis В. J Hepatol. 2010 Apr;52(1):S223-4.
29. Patin E, Kutalik Z, Guergnon J, Bibert S, Nalpas B, Jouanguy E, M, et al. Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection. Gastroenterology. 2012 Nov;143(5):1244-52.e1-12. doi: http://dx.doi.org/10.1053/j.gastro.2012.07.097

Information about authors:

Usychenko E.N. – Candidate of Medical Sciences, associate professor of the Chair of Infectious Diseases, Odessa National Medical University;
Usychenko E.M. – Candidate of Medical Sciences, associate professor of the Chair of Infectious Diseases, Odessa National Medical University;
Bazhora Y.I. – Doctor of Medical Sciences, professor, head of the Chair of Clinical Immunology, Genetics & Medical Biology, Odessa National Medical University.

Correspondence address: Ukraine, 65062, Odessa, 67A Fontanskaya doroga str.,160. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Ekaterina N. Usychenko.
                                 

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