The role of сhemokine CX3CL1/Fractalkine in chronic viral hepatitis B

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Abstract

Hepatitis B is an infectious disease resulting from infection with the hepatitis B virus. Chronic hepatitis B (CHB) is characterized by prolonged inflammation in the liver, the development of fibrosis, liver cirrhosis and hepatocellular carcinoma. Factors of the immune system play a critical role in the pathogenesis of CHB. Thanks to chemokines, immune cells migrate to the site of inflammation to implement their effector functions. The CX3CL1/Fractalkine chemokine is the only member of the CX3C family of chemokines with unique structural and functional properties. Its receptor CX3CR1 is expressed mainly on the surface of cytotoxic effector lymphocytes such as NK cells, TNK and cytotoxic T lymphocytes. The purpose of our study was to analyze the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB and the analysis of this chemokine with liver fibrosis. The concentration of CX3CL1/Fractalkine was determined in the blood plasma of patients with CHB using a multiplex assay based on xMAP technology. Blood plasma from patients with chronic viral hepatitis C (CHC) and autoimmune liver diseases (AILD) was used as a comparison group. The control group consisted of healthy individuals. For statistical analysis of data, nonparametric statistics methods were used: Kruskal–Wallis test, Spearman correlation coefficient ROC-analysis. It was shown a reduced level of CX3CL1/Fractalkine in patients with CHB compared with the control group (p = 0.0003) and with the comparison groups of CHC (p < 0.0001) and AILD (p = 0.0005). A reduced concentration of CX3CL1/Fractalkine was shown in the blood plasma of CHB patients with initial fibrosis (p = 0.0092) and severe fibrosis/cirrhosis (p = 0.0009), while in patients with severe fibrosis/cirrhosis, a significantly reduced level of this chemokine was established compared with the initial degree of liver fibrosis (p = 0.0081). Correlation analysis revealed a highly significant inverse relationship between the severity of liver fibrosis and the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB (Spearman r = –0.33; p = 0.02). Thus, the chemokine CX3CL1/Fractalkine is included in the immunopathogenesis of CHB; its reduced content is characteristic only of CHB and does not change in other chronic liver diseases. It is involved in the processes of liver fibrosis during infection with the hepatitis B virus. The concentration of the chemokine CX3CL1/Fractalkine depends on the stage of liver fibrosis in CHB, and a decrease in the level of CX3CL1/Fractalkine in the blood plasma can serve as a negative factor in the development of CHB.

About the authors

Natalia A. Arsentieva

St. Petersburg Pasteur Institute

Author for correspondence.
Email: arsentieva_n.a@bk.ru

PhD (Biology), Senior Researcher, Laboratory of Molecular Immunology

Russian Federation, 197101, St. Petersburg, Mira str., 14

O. K. Batsunov

St. Petersburg Pasteur Institute; Pavlov First Saint Petersburg State Medical University

Email: arsentieva_n.a@bk.ru

Junior Researcher, Laboratory of Molecular Immunology, Senior Laboratory Assistant, Department of Immunology

Russian Federation, 197101, St. Petersburg, Mira str., 14; St. Petersburg

N. E. Liubimova

St. Petersburg Pasteur Institute

Email: arsentieva_n.a@bk.ru

PhD (Biology), Researcher, Laboratory of Molecular Immunology

Russian Federation, 197101, St. Petersburg, Mira str., 14

V. V. Basina

St. Petersburg State Pediatric Medical University

Email: arsentieva_n.a@bk.ru

PhD (Medicine), Assistant of the Department

Russian Federation, St. Petersburg

E. V. Esaulenko

St. Petersburg Pasteur Institute; St. Petersburg State Pediatric Medical University

Email: arsentieva_n.a@bk.ru

DSc (Medicine), Professor, Head of the Viral Hepatitis Laboratory, Head of the Department of Infectious Diseases Adults and Epidemiology

Russian Federation, 197101, St. Petersburg, Mira str., 14; St. Petersburg

A. A. Totolian

St. Petersburg Pasteur Institute; Pavlov First Saint Petersburg State Medical University

Email: arsentieva_n.a@bk.ru

RAS Full Member, DSc (Medicine), Professor, Director, Head of the Department of Immunology

Russian Federation, 197101, St. Petersburg, Mira str., 14; St. Petersburg

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2. Figure 1. Concentration of the chemokine CX3CL1/Fractalkine in the blood plasma in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and autoimmune liver diseases (AILD)

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3. Figure 2. Concentration of the chemokine CX3CL1/Fractalkine in the blood plasma in patients with chronic hepatitis B (CHB) with an initial degree of liver fibrosis F0–1 and with severe fibrosis/cirrhosis F4

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4. Figure 3. ROC curves characterizing the dependence of the sensitivity and specificity of CX3CL1/Fractalkine when comparing groups of patients with CHB depending on the degree of liver fibrosis and healthy donors (HD)

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Copyright (c) 2024 Arsentieva N.A., Batsunov O.K., Liubimova N.E., Basina V.V., Esaulenko E.V., Totolian A.A.

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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