AGE-RELATED FEATURES OF SUBPOPULATION COMPOSITION AND LYMPHOCYTE METABOLISM IN CHILDREN WITH WILSON-KONOVALOV DISEASE
Original research article
Published June 25, 2023
Keywords
Wilson-Konovalov disease
Treg
Th17
liver fibrosis
lymphocyte metabolism
Treg
Th17
liver fibrosis
lymphocyte metabolism
How to Cite
Kurbatova O. V., Petrichuk S. V., Kuptsova D. G., Radygina T. V., Semikina E. L., Potapov A. S. AGE-RELATED FEATURES OF SUBPOPULATION COMPOSITION AND LYMPHOCYTE METABOLISM IN CHILDREN WITH WILSON-KONOVALOV DISEASE // Kremlin Medicine Journal. 2023. VOL. № 2. С. 5-11.
Abstract
Wilson-Konovalov disease (WD) is triggered by impairments in the copper excretion from the body leading to fatty degeneration of hepatocytes, hepatitis, fibrosis and cirrhosis of the liver. Progressing liver fibrosis is accompanied by changes in the quantitative characteristics of lymphocyte populations and their functional activity. Purpose. Assess the level of lymphocyte populations and indicators of their metabolic activity in children with Wilson-Konovalov disease.Materials and methods. 73 patients with WD, aged 6–18, and 54 age-matched healthy children were examined. Liver fibrosis stages were determined at the transient liver elastography. Subpopulation composition of peripheral blood lymphocytes was studied at flow cytometer CYTOMICS FC500. Dehydrogenase activity was assessed at cytomorphodensitometric and immunocytochemical testings. Statistical calculations were made with Statistica 10.0 program (StatSoft, USA). Results. The dependence of cellular immunity parameters on the age of children with WD was revealed: changes in percentage composition of T-lymphocytes due to the increase in cytotoxic T-lymphocytes, Thact, Th17 proportion; decrease of B-lymphocytes with age and changes in the ratio of B1 and B2 subpopulations. The absolute number of main populations decrease with age, similar to the age dynamics with the decrease in the absolute number of blood lymphocytes. Characteristic features of lymphocyte subpopulation composition in children with WD were revealed: increase of T-cell level due to T-helper population under the decrease of cytotoxic T-lymphocytes, B-lymphocytes and NK cells at the increase of Thact, Th17-lymphocytes and Treg. Children with WD had a decreased activity of lymphocyte dehydrogenases: SDH – by 27%, NADH-DH – by 16%. LDH – by 36%, if to compare with parameters of conditionally healthy children. SDH decrease was found in T-, B-lymphocytes and NK-cells. With the progressing of liver fibrosis, Treg level and SDH activity were decreasing. The largest number of patients with elevated Th17 levels was found at stages F2-3 of liver fibrosis under the maintained SDH activity. Conclusion. The revealed disorders in the lymphocyte enzyme status contribute to the understanding of pathogenesis in liver fibrosis formation and underline the need to search for possible pharmacological corrections of the revealed immunological and metabolic disorders in children with WD.References
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2. Lu Z.K. et al. Phenotypes and ATP7B gene variants in 316 children with Wilson disease // Zhonghua Er Ke Za Zhi. – 2022. – V. 60. – № 4. – Р. 317–322. doi: 10.3760/ cma.j.cn112140-20210827-00708.
3. Salman H.M. et al. Biochemical testing for the diagnosis of Wilson's disease: A systematic review // J. Clin. Lab. Anal. – 2022. – V. 36. – №. 2. – P. e24191. doi: 10.1002/ jcla.24191.
4. Przybyłkowski A. et al. Evaluation of liver fibrosis in patients with Wilson’s disease // Eur. J. Gastroenterol. Hepatol. – 2021. – V. 33. – №. 4. – P. 535–540. doi: 10.1097/MEG.0000000000001754.
5. Dev S. et al. Wilson Disease: Update on Pathophysiology and Treatment // Fron. Cell Dev. Biol. – 2022. – V. 10 – № 871877. – Р. 1–8. doi: 10.3389/fcell.2022.871877.
6. Roehlen N. et al. Liver fibrosis: mechanistic concepts and therapeutic perspectives // Cells. – 2020. – V. 9. – №. 4. – P. 875. doi: 10.3390/cells9040875.
7. Kurbatova O.V. et al. Characterisrics of the T-cell immunity in children with glycogen storage disease // Russian Journal of Immunology. – 2014. – V. 8. – №. 3. – P. 331–334. In Russian.
8. Kurbatova O.V. et al. Features of immune status in children with Wilson–Konovalov disease at different stages of liver fibrosis // Russian Journal of Immunology. – 2022. – V. 25. – № 4. – Р. 453–460. In Russian. doi: 10.46235/1028-7221- 1193-FOI.
9. Angajala A. et al. Diverse roles of mitochondria in immune responses: novel insights into immunometabolism // Front. Immunol. – 2018. – V. 9. – № 1605. – Р. 1–19. doi: 10.3389/fimmu.2018.01605.
10.Ron-Harel N. et al. Mitochondrial metabolism in T cell activation and senescence: a mini-review // Gerontology. – 2015. – V. 61. – №. 2. – P. 131–138. doi: 10.1159/000362502.
11. Steinert E.M. et al. Mitochondrial metabolism regulation of t cell-mediated immunity // Annu. rev. immunol. – 2021. – V. 39. – P. 395–416. doi: 10.1146/annurevimmunol-101819-082015.
12. Faas M.M. de Vos P. Mitochondrial function in immune cells in health and disease // Biochim. Biophys. Acta. Mol. Basis. Dis. – 2020. – V. 1866. – № 10. – Р. 1–13. doi:10.1016/j.bbadis.2020.165845.
13. Kolman J. et al. Visual biochemistry. – Moscow: Binom. Lab. knowledge. – 2011. – P. 469. In Russian.
14. Petrichuk S.V. et al. Method for measuring the mitochondrial activity of lymphocytes. – Patent for invention RU 2302635 C1, 10.07.2007. – Application No. 2005141145/15 dated 12/28/2005. In Russian.
15. Radygina T.V. et al. Quantification of lymphocyte respiratory chain enzymes by multiplex analysis // Russian Journal of Immunology. – 2017. – V.11 (20). –№4. – P. 753–755. In Russian.
16. Voss K. et al. A guide to interrogating immunometabolism // Nat. rev. Immunol. – 2021. – V. 21. – № 10. – Р. 637–652. doi: 10.1038/s41577-021-00529-8.
17. Komakh Yu.A. et al. Metabolic therapy of predicted complications in immunocompromised recipients before repeated corneal transplantation // Russian Journal of Immunology. – 2021. – Vol. 24. – № 4. – Р. 495–500. In Russian. doi: 10.46235/1028-7221-1076-MTO.
18. Boyko A.N. et al. The role of mitochondria in pathological mechanisms of innate immunity in multiple // Journal of Neurology and Psychiatry. C.C. Korsakov. – 2020. –V.120. – № 7-2. – Р. 32–37. In Russian. doi: 10.17116/jnevro202012007232.
19. Kokolina V.F. et al. Immunology of childhood // A practical guide to childhood diseases. – M.: Medpraktika. – 2006. – T. 8. – Р. 432. In Russian. 20.Кулебина Е.А. и др. Валидация показателей транзиентной эластографии для оценки стадии фиброза печени у детей // Лечащий Врач. – 2020. – № 8. – С. 57–60. doi: 10.26295/OS.2020.26.84.009.
21. Khaydukov S.V. The Standardized technology: "Study of the subpopulation composition of peripheral blood lymphocytes using flow cytofluorometer-analyzers" // Russian Journal of Immunology. – 2014. – V. 8. – № 4 (17). – P. 974–992. In Russian.
22. Toptygina A.P. et al. Age-dependent changes of T-regulatory and Th17 subset levels in peripheral blood from healthy humans // Medical Immunology. – 2017. – V. 19. – № 4. – Р. 409–420. In Russian. doi: 10.15789/1563-0625- 2017-4-409-420.
23. Gebru Y.A. et al. T Cell Subsets and Natural Killer Cells in the Pathogenesis of Nonalcoholic Fatty Liver Disease // Int. J. Mol. Sci.– 2021. – V. 22. – № 12190. – Р. 1–15. doi: 10.3390/ijms222212190.
24. Li N. et al. Interleukin-17 in Liver Disease Pathogenesis // Semin. liver dis. – 2021. – V. 41. – №4. – Р. 507–515. doi: 10.1055/s-0041-1730926.
25.Cooper J. et al. Liver Disease: Nonalcoholic Fatty Liver Disease // FP essentials. – 2021. – V. 511. – P. 29–35.