Subpopulations of circulating monocytes as potential biomarkers of disease severity in patients with viral liver cirrhosis


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Abstract

Viral hepatitis remains the most common cause of liver cirrhosis (LC). Monocytes, capable of migrating to the liver and participating in inflammation and fibrogenesis, play an important role in the pathogenesis of LC, which is confirmed by the association of certain monocyte subpopulations with the disease severity and mortality in alcoholic and biliary LC. However, in viral LC the clinical and prognostic relevance of monocytes has been less investigated. This study aimed to investigate the disturbances of circulating monocytes including classical (CD14 ++CD16−, cMo), intermediate (CD14++CD16+, iMo) and non-classical monocytes (CD14+CD16++, nMo) in patients with viral LC, as well as the correlation of these cells with viral characteristics, LC severity and the progression of the disease 12 months following complex therapy. It was revealed a significant increase in iMo and nMo, a tendency to decrease of cMo, and a two-fold reduction in cMo/iMo ratio in patients with viral LC compared to healthy donors. These changes in monocyte pattern did not depend on the type of virus (HCV against HBV/HDV) and virus replication (replication against the integrative phase), but were associated with the LC severity. The proportion of iMo was positively correlated with laboratory indicators of liver damage, Chaild-Pugh (RS=0.57; P=0.001) and MELD score (RS=0.41; P=0.033). ROC analysis showed that the cMo/iMo ratio at the values ​​of <9.5 allowed to predict the risk of LC progression with a sensitivity of 83.3% and a specificity of 76.2%. Of note, patients with alcoholic or biliary/autoimmune LC in comparison groups also demonstrated increased frequencies in iMo and nMo and decreased cMo/iMo ratio. However, in this case, the LC severity was negatively correlated with CD16+monocytes, in particular, with the iMo and nMo subset, respectively, in alcoholic and biliary LC, evidencing the protective role of these subpopulations. Conclusion:  in viral LC the changes in circulating monocytes towards an increase in iMO and nMo and decrease in cMo are not associated with the virus type and replication; in contrast to the alcoholic and biliary/autoimmune LC, the proportion of iMo directly correlates with the indicators of liver damage and LC severity; cMo/iMo ratio is a biomarker of therapy response/disease progression.

About the authors

Olga Leplina

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Author for correspondence.
Email: oleplina@mail.ru
ORCID iD: 0000-0003-3169-8643

PhD, MD (Medicine), Leading Research Associate, Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Russian Federation

Marina Tikhonova

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: martix-59@mail.ru
ORCID iD: 0000-0002-7987-2017

PhD (Biology), Senior Research Associate, Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Ilona Meledina

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: ilonameledina@gmail.com
ORCID iD: 0000-0003-0463-0002

PhD (Medicine), Head of the Immunology Department, Clinics of Immunopathology, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Olga Zheltova

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: olzheltova@mail.ru
ORCID iD: 0000-0003-3656-2630

PhD (Medicine), Immunologist, Immunology Department, Clinics of Immunopathology, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Ekaterina Shevela

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: shevelak@mail.ru
ORCID iD: 0000-0001-8997-3586

PhD, MD (Medicine), Leading Research Associate, Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Alexander Ostanin

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: ostanin62@mail.ru
ORCID iD: 0000-0001-6895-938X

PhD, MD (Medicine), Professor, Main Research Associate, Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Elena Chernykh

Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Email: ct_lab@mail.ru
ORCID iD: 0000-0003-2346-6279

RAS Corresponding Member, PhD, MD (Medicine), Professor, Head, Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

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Copyright (c) 2022 Leplina O., Tikhonova M., Meledina I., Zheltova O., Shevela E., Ostanin A., Chernykh E.

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