Features of the immunoreactivity T and B lymphocytes subpopulations and cytokine imbalance in patients with hepatosplenomegaly of different etiology

Authors

DOI:

https://doi.org/10.14739/2310-1237.2021.2.229454

Keywords:

hepatosplenomegaly, trigger factor, immunoreactivity, cytokines, lymphocyte subpopulations, B lymphocytes, T lymphocytes

Abstract

The aim was to study the mechanisms of immunological dysregulation of cytokine and immunoglobulin production, changes in the CD expression of T and B lymphocyte subpopulations in patients with hepatosplenomegaly of different etiology.

Materials and methods. We examined 73 patients with liver cirrhosis complicated by portal hypertension, hepatosplenomegaly, and bleeding from phlebectasia. We identified three groups of patients depending on the triggering factors of cirrhosis: the first (I) group – HBV/HCV; the second (II) group – CMV/VEB; the third (III) group – hereditary enzymopathies. The study material was lymphocytes and blood serum. We used the methods of ELISA, immunofluorescence and flow cytometry.

Results. An increase in the concentration of IgA and IgM was revealed against the background of normal number of CD22+ B lymphocytes with HBV/HCV (I group), high level of IgM and their producers, B lymphocytes, with CMV/VEB (II group), in group III with hereditary enzymopathies, the concentration of all immunoglobulins was normal with an increased content of B lymphocytes. Multidirectional changes in the content of cytokines were revealed: in group I the synthesis of anti-inflammatory cytokines IL-4, IL-10 and in group II – pro-inflammatory IL-1β, INF-γ, TNF-α dominated; in group III the concentration of IL-6 and vascular growth factor (VEGF) was maximally increased. The number of activated CD3+CD4+CD25+ T cells was reduced in groups I and II – by 2.3 and 2.0 times respectively, in group III – increased by 1.2 times. The number of regulatory T lymphocytes CD3+CD4+CD25+CD127neg was reduced by half in I and II groups. Expression of co-stimulatory molecules CD3+CD4+CD28+ was low in all groups and the maximum decrease was in group III. In patients with HCV/HBV, an increase in the expression of the late activation marker of lymphocytes CD3+HLA-DR+ by an average of 63 % was noted.

Conclusions. The revealed immune disorders in hepatosplenomegaly of different etiology are characterized by multidirectional changes. Approaches to the treatment of these patients should be complex, taking into account the trigger factors that cause dysregulation of immune responses, which leads to further destruction, and focuses at remodeling target organs.

Author Biographies

O. M. Klimova, SI “Zaitsev V. T. Institute of General and Urgent surgery of NAMS of Ukraine”, Kharkiv

PhD, DSc, Professor, Head of Diagnostic Laboratory with Enzyme Immunoassay and Immunofluorescence Analysis; Professor of the Department of Molecular Biology and Biotechnology, V. N. Karazin Kharkiv National University, Ukraine

T. I. Kordon, SI “Zaitsev V. T. Institute of General and Urgent Surgery of NAMS of Ukraine”, Kharkiv

PhD, Senior Researcher, Diagnostic Laboratory with Enzyme Immunoassay and Immunofluorescence Analysis

S. V. Sushkov, SI “Zaitsev V. T. Institute of General and Urgent Surgery of NAMS of Ukraine”, Kharkiv

MD, PhD, DSc, Professor, Deputy Director for Research

L. A. Drozdova, SI “Zaitsev V. T. Institute of General and Urgent Surgery of NAMS of Ukraine”, Kharkiv

PhD, Senior Researcher, Diagnostic Laboratory with Enzyme Immunoassay and Immunofluorescence Analysis

O. V. Lavinska, SI “Zaitsev V. T. Institute of General and Urgent Surgery of NAMS of Ukraine”, Kharkiv

PhD, Senior Researcher, Diagnostic Laboratory with Enzyme Immunoassay and Immunofluorescence Analysis

O. S. Merezhko, SI “Zaitsev V. T. Institute of General and Urgent Surgery of NAMS of Ukraine”, Kharkiv

Junior Researcher, Diagnostic Laboratory with Enzyme Immunoassay and Immunofluorescence Analysis; Laboratory Assistant of the Department of Molecular Biology and Biotechnology, V. N. Karazin Kharkiv National University, Ukraine

K. O. Bychenko, SI “Zaitsev V. T. Institute of General and Urgent surgery of NAMS of Ukraine”, Kharkiv

Junior Researcher, Diagnostic Laboratory with Enzyme Immunoassay and Immunofluorescence Analysis; Postgraduate Student of the Department of Molecular Biology and Biotechnology, V. N. Karazin Kharkiv National University, Ukraine

References

Albillos, A., Lario, M., & Alvarez-Mon, M. (2014). Cirrhosis-associated immune dysfunction: Distinctive features and clinical relevance. Journal of hepatology, 61, 1385-1396. https://doi.org/10.1016/j.jhep.2014.08.010

Hu, X., Huang, X., Hou, J., Ding, L., Su, C., & Meng, F. (2020). Diagnostic accuracy of spleen stiffness to evaluate portal hypertension and esophageal varices in chronic liver disease: a systematic review and meta-analysis. European Radiology, 31, 2392-2404. https://doi.org/10.1007/s00330-020-07223-8

Dinarello, C. A. (2018). Overview of the IL-1 family in innate inflammation and acquired immunity. Immunology Review, 281(1), 8-27. https://doi.org/10.1111/imr.12621

Engelmann, C., Sheikh, M., Sharma, S., Gupta, S., Andreola, F., & Jalan, R. (2020). Toll-like receptor 4 is a therapeutic target for prevention and treatment of liver failure. Journal of hepatology, 73(1), 102-112. https://doi.org/10.1016/j.jhep.2020.01.011

Ciesielcka, A., Matyjek, M., & Kwiatkowska, K. (2021). TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cellular and molecular life sciences, 78, 1233-1261. https://doi.org/10.1007/s00018-020-03656-y

Li, L., Duan, M., Chen, W., Jiang, A., Li, X., Yang, J., & Li, Z. (2017). The spleen in liver cirrhosis: revisiting an old enemy with novel targets. Journal of translational medicine, 15(1), 111. https://doi.org/10.1186/s12967-017-1214-8

Klimova, O. M., Sushkov, S. V., Timcenko, M. E., Riabcev, R. S., Kordon, T. I., Bychenko, E. A., & Merezhko, O. S. (2019). Immunoreactivity changes in patients with gastrointestinal pathology against the background of chronic Helicobacter pylori infection. Surgery (Azerbaijan Republic), (4), 29-37.

Klimova, O., Kordon, T., Smachylo, R., BelozоrovI., Bychenko, E., Merezhko, O., & Kudrevych, O. (2019). Dyferentsialna diahnostyka i korektsiia metabolichnykh ta imunolohichnykh porushen u khvorykh z tsyrozom pechinky, uskladnenym hepatosplenomehaliieiu ta portalnoiu hipertenziieiu [Differential diagnostics and correction of metabolic and immunological disorders in patients with hepatic cirrhosis, complicated hepatosplenomegalia and portal hypertension]. Actual Problems of Modern Medicine, (4), 31-41. [in Ukrainian]. https://doi.org/10.26565/2617-409X-2019-4-04

Klimova, E. M., Kalashnikova, Y. V., Kordon, T. I., Lavinskaya, E. V., Agarkova, A. N., Osmanov, R. R., & Ryabinskaya, O. V. (2020). Prediktory gemorragicheskikh i tromboticheskikh oslozhnenii sindroma gepatosplenomegalii [Predictors of hemorrhagic and thrombotic complications of hepatosplenomegaly syndrome]. Kharkiv Surgical School, (1), 148-154. [in Russian]. https://doi.org/10.37699/2308-7005.1.2020.25

Inamine, T., & Schnabl, B. (2018). Immunoglobulin A and liver diseases. Journal of gastroenterology, 53(6), 691-700. https://doi.org/10.1007/s00535-017-1400-8

Takada, D., Sumida, K., Sekine, A., Hazue, R., Yamanouchi, M., Suwabe, T., Hayami, N., Hoshino, J., Sawa, N., Takaichi, K., Fujii, T., Ohachi, K., & Ubara, Y. (2017). IgA nephropathy featuring massive wire loop-like deposits in two patients with alcoholic cirrhosis. BMC Nephrology, 18(1), 362. https://doi.org/10.1186/s12882-017-0769-1

Oliveira, F. L., Bernardes, E. S., Brand, C., dos Santos, S. N., Cabanel, M. P., Arcanjo, K. D., Brito, J. M., Borojevic, R., Chammas, R., & El-Cheikh, M. C. (2016). Lack of galectin-3 up-regulates IgA expression by peritoneal B1 lymphocytes during B cell differentiation. Cell and tissue research, 363(2), 411-426. https://doi.org/10.1007/s00441-015-2203-y

Taylor, S. A., Assis, D. N., & Mack, C. L. (2019). The Contribution of B Cells in Autoimmune Liver Diseases. Seminars in Liver Disease, 39(4), 422-431. https://doi.org/10.1055/s-0039-1688751

Kawaratani, H., Tsujimoto, T., Douhara, A., Takaya, H., Moriya, K., Namisaki, T., Noguchi, R., Yoshiji, H., Fujimoto, M., & Fukui, H. (2013). The effect of inflammatory cytokines in alcoholic liver disease. Mediators of Inflammation, 2013, 495156. https://doi.org/10.1155/2013/495156

Topolyanskaya, S. V. (2020). Rol' interlejkina 6 pri starenii i vozrast associirovannyh zabolevanijah [Interleukin 6 in aging and age-related diseases]. Klinitsist, 14(3-4), 10-17. [in Russian]

Horst, A. K., Kumashie, K. G., Neumann, K., Diehl, L., & Tiegs, G. (2021). Antigen presentation, autoantibody production, and therapeutic targets in autoimmune liver disease. Cellular & molecular immunology, 18(1), 92-111. https://doi.org/10.1038/s41423-020-00568-6

Pinto, C., Giordano, D. M., Maroni, L., & Marzioni, M. (2018). Role of inflammation and proinflammatory cytokines in cholangiocyte pathophysiology. Biochimica et biophysica acta. Molecular basis of disease, 1864(4 Pt B), 1270-1278. https://doi.org/10.1016/j.bbadis.2017.07.024

Ferreira, C. R, & Gahl, W. A. (2017). Lysosomal storage diseases. Тranslational Scince of rare disease, 2(1-2), 1-71. https://doi.org/10.3233/TRD-160005

Ivanova, M., Limgala, R. P., Changsila, E., Kamath, R., Ioanou, C., & Goker-Alpan, O. (2018). Gaucheromas: When macrophages promote tumor formation and dissemination. Blood cells, molecules & diseases, 68, 100-105. https://doi.org/10.1016/j.bcmd.2016.10.018

Karkhad, A., Javanian, M., & Ebrahimpour, S. (2018). The role of regulatory T cells in immunopathogenesis and immunotherapy of viral infections. Infection, Genetics and Evolution, 59, 32-37. https://doi.org/10.1016/j.meegid.2018.01.015

Dominguez-Villar, M., & Hafler, D. A. (2018). Regulatory T cells in autoimmune disease. Nature Immunology, 19(7), 665-673. https://doi.org/10.1038/s41590-018-0120-4

Van der Heide, D., Weiskirchen, R., & Bansal, R. (2019). Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases. Frontiers in immunology, 10, 2852. https://doi.org/10.3389/fimmu.2019.02852

Liberal, R., Grant, C. R., Longhi, M. S., Mieli-Vergani, G., & Vergani, D. (2015). Regulatory T cells: Mechanisms of suppression and impairment in autoimmune liver disease. IUBMB life, 67(2), 88-97. https://doi.org/10.1002/iub.1349

Burghardt, S., Claass, B., Erhardt, A., Karimi, K., & Tiegs, G. (2014). Hepatocytes induce Foxp3⁺ regulatory T cells by Notch signaling. Journal of leukocyte biology, 96(4), 571-577. https://doi.org/10.1189/jlb.2AB0613-342RR

Robinson, M. W., Harmon, C., & O'Farrelly, C. (2016). Liver immunology and its role in inflammation and homeostasis. Cellular & molecular immunology, 13(3), 267-276. https://doi.org/10.1038/cmi.2016.3

Oba, R., Isomura, M., Igarashi, A., & Nagata, K. (2019). Circulating CD3+HLA-DR+ Extracellular Vesicles as a Marker for Th1/Tc1-Type Immune Responses. Journal of immunology research, 2019, 6720819. https://doi.org/10.1155/2019/6720819

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Published

2021-08-20

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1.
Klimova OM, Kordon TI, Sushkov SV, Drozdova LA, Lavinska OV, Merezhko OS, Bychenko KO. Features of the immunoreactivity T and B lymphocytes subpopulations and cytokine imbalance in patients with hepatosplenomegaly of different etiology. Pathologia [Internet]. 2021Aug.20 [cited 2024Nov.8];18(2):174-82. Available from: http://pat.zsmu.edu.ua/article/view/229454

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Original research