Features of parameters of cellular immune depending on the activity of foci of demyelination in children with multiple sclerosis
https://doi.org/10.15789/1563-0625-FOP-2777
Abstract
MS is a common disease of the central nervous system that leads to disability and reduced quality of life. The debut of disease in 3-5% of patients occurs in childhood and has a less favorable course compared to adults. MS is caused by the activation of autoreactive T cells in the breakdown of peripheral tolerance, which is normally controlled by regulatory T cells (Tregs). It is promising to study expression of CD39 and CD73 in Treg and Th17 populations to assess their suppressive activity. Aim is to evaluate content of major and minor lymphocyte populations and expression of CD39 and CD73 in CD4+ lymphocyte population in children with MS. 111 children with MS were examined, 66 with contrast-negative lesions on MRI (Group 1), 45 with contrast-positive lesions (Group 2). The comparison group consisted of 46 healthy children (Group 3). Content of T, B, NK lymphocytes, Treg (CD4+CD25highCD127low), Thact (CD4+CD25highCD127high), Th17 cells (CD3+CD4+CD161+); expression of CD39 and CD73 in Treg, Th17 and Thact was performed by flow cytometry. An increase in content of T helpers, a decrease in NK cells in patients in group 2 was revealed. An increase in number of Thact and Th17 lymphocytes was obtained in patients of both groups with MS. Number of Tregs in group 1 was significantly higher than in group 3. Ratio of cells expressing CD39 and CD73 in MS patients depended on lymphocyte population as well as in the group 3. The highest content of CD39+ cells was observed in Treg population, and the lowest in Thact population. For CD73 expression, on the contrary, the highest expression of CD73 was observed in Thact cells, the lowest in Treg. When comparing groups of patients, it was found that in patients of group 1, number of cells expressing CD39 ectonucleotidase was significantly increased, and number of supTh17 was comparable with group 3. In both groups of MS patients, an increase in CD73 counts in Treg, Thact and Th17 was observed. Thus, informative populations of lymphocytes (CD4+ cells, Treg, CD39+Treg, supTh17) have been identified, which can be used to monitor condition of children with multiple sclerosis.
Keywords
About the Authors
T. V. RadyginaRussian Federation
Tatiana V. Radygina - PhD (Medicine), Senior Research Associate, Laboratory of Experimental Immunology and Virology, National Medical Research Center of Children's Health.
2 Lomonosovsky Ave, Bldg 1 Moscow 119991
Phone: +7 (499) 134-13-98. Fax: +7 (499) 134-70-01
Competing Interests:
No conflict of interest
D. G. Kuptsova
Russian Federation
Daria G. Kuptsova - Junior Research Associate, Laboratory of Experimental Immunology and Virology, National Medical Research Center of Children's Health.
Moscow
Competing Interests:
No conflict of interest
O. V. Kurbatova
Russian Federation
Olga V. Kurbatova - PhD (Medicine), Senior Research Associate, Laboratory of Experimental Immunology and Virology, National Medical Research Center of Children's Health.
Moscow
Competing Interests:
No conflict of interest
S. V. Petrichuk
Russian Federation
Svetlana V. Petrichuk - PhD, MD (Biology), Professor, Chief Research Associate, Laboratory of Experimental Immunology and Virology, National Medical Research Center of Children's Health.
Moscow
Competing Interests:
No conflict of interest
E. L. Semikina
Russian Federation
Elena L. Semikina - PhD, MD (Medicine), Head, Laboratory Department, Chief Research Associate, Laboratory of Experimental Immunology and Virology, National Medical Research Center of Children's Health; Professor, Department of Pediatrics and Pediatric Rheumatology, I. Sechenov First Moscow State Medical University (Sechenov University).
Moscow
Competing Interests:
No conflict of interest
A. P. Fisenko
Russian Federation
Andrey P. Fisenko - PhD, MD (Medicine), Professor, Director, National Medical Research Center of Children's Health.
Moscow
Competing Interests:
No conflict of interest
L. M. Abdullaeva
Russian Federation
Luizat M. Abdullaeva - Junior Research Associate, Laboratory of Rare Hereditary Diseases in Children of the Medical Genetic Center, Neurologist of the Department of Psychoneurology and Psychosomatic Pathology, National Medical Research Center of Children's Health.
Moscow
Competing Interests:
No conflict of interest
B. I. Bursagova
Russian Federation
Bella I. Bursagova - PhD (Medicine), Senior Research Associate, Laboratory of Nervous Disorders, Deputy for Medical Work, Department of Psychoneurology and Psychosomatic Pathology, National Medical Research Center of Children's Health.
Moscow
Competing Interests:
No conflict of interest
References
1. Alroughani R., Boyko A. Pediatric multiple sclerosis: a review. BMC Neurol., 2018, Vol. 18, no. 1, 27. doi: 10.1186/s12883-018-1026-3.
2. Álvarez-Sánchez N., Cruz-Chamorro I., Díaz-Sánchez M., Lardone P.J., Guerrero J.M., Carrillo-Vico A. Peripheral CD39-expressing T regulatory cells are increased and associated with relapsing-remitting multiple sclerosis in relapsing patients. Sci. Rep., 2019, Vol. 9, 2302. doi: 10.1038/s41598-019-38897-w.
3. Baecher-Allan C., Kaskow B.J., Weiner H.L. Multiple sclerosis: mechanisms and immunotherapy. Neuron, 2018, Vol. 97, no. 4, pp. 742-768.
4. Borsellino G., Kleinewietfeld M., di Mitri D., Sternjak A., Diamantini A., Giometto R., Hopner S., Cento nze D., Bernardi G., DellAcqua M.L., Rossini P.M., Battistin L., Rotzschke O., Falk K. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood, 2007, Vol. 110, no. 4, pp. 1225-1232.
5. Dendrou C., Fugger, L., Friese M. Immunopathology of multiple sclerosis. Nat. Rev. Immunol., 2015, Vol. 15, pp. 545-558.
6. Fernandez D., Flores-Santibanez F., Neira J., Osorio-Barrios F., Tejon G., Nunez S., Hidalgo Y., Fuenzalida M.J., Meza D., Ureta G., Lladser A., Pacheco R., Acuna-Castillo C., Guixe V., Quintana F.J., Bono M.R., Rosemblatt M., Sauma D. Purinergic signaling as a regulator of Th17 Cell Plasticity. PLoS One, 2016, Vol. 11, no. 6, e0157889. doi: 10.1371/journal.pone.0157889.
7. Friess J., Hecker M., Roch L., Koczan D., Fitzner B., Angerer I., Schroder I., Flechtner K., Thiesen H-J., Winkelmann A., Zettl U. Fingolimod alters the transcriptome profile of circulating CD4+ cells in multiple sclerosis. Sci. Rep., 2017, Vol. 7, 42087. doi: 10.1038/srep42087.
8. Kulikova S., Kuzniatsova A., Likhachev S., Golets Y. Pediatric multiple sclerosis: diagnostics and treatment (Review). Neurology and Neurosurgery. Eastern Europe, 2021, Vol. 11, no. 1, pp. 69-81. (In Russ.)
9. Kunkl M., Frascolla S., Amormino C., Volpe E., Tuosto L. T helper cells: the modulators of inflammation in multiple sclerosis. Cells, 2020, Vol. 9, no. 2, 482. doi: 10.3390/cells9020482.
10. Ochoa-Reparaz J., Kasper L. H. The influence of gut-derived CD39 regulatory T cells in CNS demyelinating disease. Transl. Res., 2017, Vol. 179, pp. 126-138.
11. Patsopoulos N.A. Genetics of multiple sclerosis: an overview and new directions. Cold Spring Harb. Perspect. Med., 2018, Vol. 8, no. 7, a028951. doi: 10.1101/cshperspect.a028951.
12. Preiningerova J.L., Jiraskova Zakostelska Z., Srinivasan A., Ticha V., Kovarova I., Kleinova P., Tlaskalova- Hogenova H., Kubala Havrdova E. Multiple sclerosis and microbiome. Biomolecules, 2022, Vol. 12, no. 3, 433. doi: 10.3390/biom12030433.
13. Radygina T.V., Kuptsova D.G., Petrichuk S.V., Semikina E.L., Fisenko A.P. Expression of CD39 and CD73 ectonucleotidases in CD4+ lymphocyte populations in healthy children. Russian Journal of Immunology, 2022, Vol. 25, no. 2, pp. 337-344. (In Russ.)
14. van Langelaar J., Rijvers L., Smolders J., van Luijn M.M. B and T cells driving multiple Sclerosis: mechanisms and potential triggers. Front. Immunol.,2020, Vol. 11, 760. doi: 10.3389/fimmu.2020.00760.
15. Walton C., King R., Rechtman L., Kaye W., Leray E., Marrie R.A., Robertson N., La Rocca N., Uitdehaag B., van der Mei I., Wallin M., Helme A., Angood Napier C., Rijke N., Baneke P. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult. Scler., 2020, Vol. 26, no. 14, pp. 1816-1821.
Supplementary files
Review
For citations:
Radygina T.V., Kuptsova D.G., Kurbatova O.V., Petrichuk S.V., Semikina E.L., Fisenko A.P., Abdullaeva L.M., Bursagova B.I. Features of parameters of cellular immune depending on the activity of foci of demyelination in children with multiple sclerosis. Medical Immunology (Russia). 2023;25(5):1019-1026. https://doi.org/10.15789/1563-0625-FOP-2777