Role of minor lymphocyte populations in development of liver fibrosis in children with glycogen storage disease

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Abstract

Glycogen storage disease (GSD) is a rare condition that changes the way the body uses and stores glycogen. Objective: to evaluate the content of small populations of lymphocytes and their ratios in children with hepatic forms of glycogen disease depending on the stage of liver fibrosis. 148 children with GSD at the age of Me=7,7 [3,9;11,8] were examined. The comparison group consisted of 54 healthy children. The stage of liver fibrosis was carried out on the FibroScan F502 device (EchoSence, France). Immunophenotyping of lymphocytes was performed on CYTOMICS FC500 (Beckman Coulter, USA). Indicators of lymphocyte populations were analyzed as a percentage of deviation from the age norm. In children with GSD, an increase in the degree of liver fibrosis was revealed from age (R=0.57). Treg content in children with GSD was at the lower limit of the age norm and did not depend on the stage of liver fibrosis. The content of Th17 and Thact lymphocytes was significantly higher than that of the comparison group at all stages of liver fibrosis, starting from stage F1. With an increase in the stage of liver fibrosis, there was an increase in the proportion of patients with Thact and Th17 content exceeding the upper limit of the normative values (PF0-F4=0.021 and PF0-F4=0.012, respectively). An increase in Th17/Treg and Thact/Treg ratios was revealed in patients with GSD relative to the comparison group in all age groups, the dynamics of Th17/Treg and Thact/Treg ratios was characterized by their increase with age. Analysis of indicators depending on the stage of liver fibrosis in children with GSD revealed a significant increase in the Thact/Treg ratio from stage F0 to stages F1, F2, F3 and F4 (PF0-F4=0.000). The Th17/Treg index increased from stage F0 to stages F1, F2, F3 (PF0-F3=0.000).

An increase in the content of Thact and Th17 lymphocytes, as well as Th17/Treg and Thact/Treg indices with an increase in the stage of liver fibrosis can be used as an additional tool in assessing fibrotic changes in the liver. Immunological indicators objectively reflect the severity of the patient's condition with hepatic forms of GSD.

About the authors

Olga V. Kurbatova

National Medical Research Center for Children’s Health

Author for correspondence.
Email: putintseva@mail.ru
ORCID iD: 0000-0002-9213-5281

Ph.D. (Medicine) Senior Researcher, Laboratory of Experimental Immunology and Virology

Russian Federation, 2/1 Lomonosovsky Ave, Moscow, 119991

Svetlana V. Petrichuk

National Medical Research Center for Children’s Health

Email: cito@list.ru
ORCID iD: 0000-0003-0896-6996

Chief Researcher, Laboratory of Experimental Immunology and Virology

Russian Federation, 2/1 Lomonosovsky Ave, Moscow, 119991

Goar B. Movsisyan

National Medical Research Center for Children’s Health

Email: movsisyan@nczd.ru
ORCID iD: 0000-0003-2881-4703

Senior Researcher of the Laboratory of Rare Hereditary Diseases, Gastroenterologist of the Gastroenterology Department with the Hepatological Group

Russian Federation, 2/1 Lomonosovsky Ave, Moscow, 119991

Daria G. Kuptsova

National Medical Research Center for Children’s Health

Email: dg.kuptsova@gmail.com
ORCID iD: 0000-0001-7771-3314

Junior Researcher, Clinical Laboratory Physician, Laboratory of Experimental Immunology and Virology

Russian Federation, 2/1 Lomonosovsky Ave, Moscow, 119991

T. V. Radygina

National Medical Research Center for Children’s Health

Email: tvradigina@mail.ru
ORCID iD: 0000-0003-4704-6885

Ph.D. (Medicine), Senior Researcher, Laboratory of Experimental Immunology and Virology

Russian Federation, 2/1 Lomonosovsky Ave, Moscow, 119991

A. O. Anushenko

National Medical Research Center for Children’s Health

Email: anoushenko@gmail.com
ORCID iD: 0000-0002-1549-2728

Gastroenterologist of the Gastroenterology Department with the Hepatological Group

Russian Federation, 2/1 Lomonosovsky Ave, Moscow, 119991

Elena L. Semikina

National Medical Research Center for Children’s Health; I. Sechenov First Moscow State Medical University

Email: semikinaelena@yandex.ru
ORCID iD: 0000-0001-8923-4652

PhD, MD (Medicine), Professor, Chief Research Associate, Laboratory of Research in Pediatric Gastroenterology and Hepatology, Head of Gastroenterology Department with Hepatology Group, Professor, Department of Pediatrics and Pediatric Rheumatology

Russian Federation, 2/1 Lomonosovsky Ave, Moscow, 119991; 8/2, st. Trubetskaya, Moscow, 119991

A. S. Potapov

National Medical Research Center for Children’s Health; I. Sechenov First Moscow State Medical University

Email: potapov@nczd.ru
ORCID iD: 0000-0003-4905-2373

PhD, MD (Medicine), Professor, Chief Scientist, Laboratory of scientific foundations of pediatric gastroenterology and hepatology, Head of Gastroenterology Department with Hepatology Group, professor of the Department of Pediatrics and Pediatric Rheumatology

Russian Federation, 2/1 Lomonosovsky Ave, Moscow, 119991; 8/2, st. Trubetskaya, Moscow, 119991

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Supplementary files

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2. Figure 1. The content of Treg, That, Treg cells (% of CD4) in children with glycogen disease, depending on the stage of liver fibrosis, as a percentage of age normative values. Note: the range of normative values is marked with a dotted line, reliable differences between groups are shown below the figures.

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3. Figure 2. Dynamics of changes in the ratio of Th17/Treg (a) and Thact/Treg (b) with age in children with GSD and in the comparison group, changes in the indices of Th17/Treg and Thact/Treg depending on the stage of liver fibrosis (c).

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Copyright (c) 2023 Kurbatova O.V., Petrichuk S.V., Movsisyan G.B., Kuptsova D.G., Radygina T.V., Anushenko A.O., Semikina E.L., Potapov A.S.

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