Activity of the nuclear transcription factor NF-κB in lymphocyte populations in children with Gaucher disease
- Authors: Konyashin M.V.1, Kurbatova O.V.1, Petrichuk S.V.1, Movsisyan G.B.1, Freidlin E.V.1, Kuptsova D.G.1, Radygina T.V.1, Semikina E.L.1,2, Potapov A.S.1,2, Fisenko A.P.1
-
Affiliations:
- National Medical Research Center for Children’s Health
- Sechenov First Moscow State Medical University, Russian Academy of Sciences
- Issue: Vol 28, No 3 (2025)
- Pages: 597-604
- Section: SHORT COMMUNICATIONS
- URL: https://journals.rcsi.science/1028-7221/article/view/319907
- DOI: https://doi.org/10.46235/1028-7221-17203-AOT
- ID: 319907
Cite item
Full Text
Abstract
The study is devoted to the role of the transcription factor NF-κB in pathogenesis of chronic inflammation in Gaucher disease (GD) in children. Gaucher disease is an orphan autosomal recessive lysosomal disorder characterized by mutations in the β-glucocerebrosidase gene, leading to a decrease in the activity of this enzyme and, as a consequence, to the accumulation of the substrate – glucoceramide. Macrophages transformed to Gaucher cells, due to the accumulation of glucoceramide, secrete proinflammatory cytokines (IL-1β, IL-6, TNFα), triggering chronic inflammation in internal organs via activation of NF-κB nuclear transcription factor along the canonical pathway. The aim of the work was to assess the proportion of cells with the activity of the nuclear transcription factor NF-κB in lymphocyte populations in children with GD. The ratio of cells with NF-κB translocation in peripheral blood lymphocyte populations was assessed in 70 GD patients (type 1, 58 cases; type 3, 12 patients) receiving enzyme replacement therapy, and in 30 conditionally healthy children. The results of the studies revealed a significantly increased proportion of cells with NF-κB translocation in T lymphocytes, T helpers, cytotoxic T cells, NK cells, B lymphocytes, as well as in T helpers type 17, activated T helpers and in regulatory T cells in GD patients compared with control group (p < 0.001). In children with GD, the highest number of cells with NF-κB translocation was found in B lymphocytes and NK cell populations. In the course of the study of patients with different types of GD, it was found that in children with type 1 GD, a significant increase in the level of NF-κB translocation was observed in all studied lymphocyte populations. In patients with type 3 GD, a significant increase in NF-κB translocation in T lymphocytes, T helpers, cytotoxic T lymphocytes, NK cells, Th17 cells, activated T helpers and regulatory T cells was also noted, relative to the comparison group. However, in the populations of B lymphocytes and double negative T lymphocytes in patients with type 3 GD, no statistically significant differences were found against the comparison group. The results of the study confirm the key role of NF-κB in maintaining chronic inflammation in Gaucher disease. Modern flow cytometry approach with visualization allows to determine NF-κB activity in different populations of peripheral blood lymphocytes, including Th17 and Treg, with high accuracy. It is advisable to conduct additional studies concerning the effect of initiated enzyme replacement therapy on NF-κB activity in lymphocyte populations of children with Gaucher disease.
Full Text
##article.viewOnOriginalSite##About the authors
Matvey V. Konyashin
National Medical Research Center for Children’s Health
Author for correspondence.
Email: matele99@mail.ru
Clinical Laboratory Doctor, Laboratory of Experimental Immunology and Virology
Russian Federation, MoscowO. V. Kurbatova
National Medical Research Center for Children’s Health
Email: matele99@mail.ru
PhD (Medicine), Senior Researcher, Laboratory of Experimental Immunology and Virology
Russian Federation, MoscowS. V. Petrichuk
National Medical Research Center for Children’s Health
Email: matele99@mail.ru
PhD, MD (Biology), Professor, Chief Researcher, Laboratory of Experimental Immunology and Virology
Russian Federation, MoscowG. B. Movsisyan
National Medical Research Center for Children’s Health
Email: matele99@mail.ru
PhD (Medicine), Senior Researcher of the Laboratory of Rare Hereditary Diseases, Gastroenterologist of the Gastroenterology Department with the Hepatological Group
Russian Federation, MoscowE. V. Freidlin
National Medical Research Center for Children’s Health
Email: matele99@mail.ru
Laboratory Assistant, Laboratory of Experimental Immunology and Virology
Russian Federation, MoscowD. G. Kuptsova
National Medical Research Center for Children’s Health
Email: matele99@mail.ru
PhD (Medicine), Junior Researcher, Clinical Laboratory Doctor, Laboratory of Experimental Immunology and Virology
Russian Federation, MoscowT. V. Radygina
National Medical Research Center for Children’s Health
Email: matele99@mail.ru
PhD (Medicine), Senior Researcher, Laboratory of Experimental Immunology and Virology
Russian Federation, MoscowE. L. Semikina
National Medical Research Center for Children’s Health; Sechenov First Moscow State Medical University, Russian Academy of Sciences
Email: matele99@mail.ru
PhD, MD (Medicine), Head, Laboratory Department; Professor, Department of Pediatrics and Pediatric Rheumatology
Russian Federation, Moscow; MoscowA. S. Potapov
National Medical Research Center for Children’s Health; Sechenov First Moscow State Medical University, Russian Academy of Sciences
Email: matele99@mail.ru
PhD, MD (Medicine), Professor, Chief Researcher of the Laboratory of Scientific Foundations of Pediatric Gastroenterology and Hepatology, Head of the Center for Inflammatory Bowel Diseases in Children, Head of Gastroenterology Department with Hepatology Group; Professor, Department of Pediatrics and Pediatric Rheumatology
Russian Federation, Moscow; MoscowA. P. Fisenko
National Medical Research Center for Children’s Health
Email: matele99@mail.ru
PhD, MD (Medicine), Professor, Director
Russian Federation, MoscowReferences
- Курбатова О.В., Мовсесян Г.Б., Коняшин М.В., Петричук С.В., Купцова Д.Г., Радыгина Т.В., Семикина Е.Л., Потапов А.С., Фисенко А.П. Возрастная динамика показателей клеточного иммунитета, активность внутриклеточных дегидрогеназ лимфоцитов и функциональная активность нейтрофилов у детей с болезнью Гоше. Вопросы гематологии/онкологии и иммунопатологии в педиатрии, 2024. Т. 23, № 1. С. 128-138. [Kurbatova O.V., Movsisyan G.B., Konyashin M.V., Petrichuk S.V., Kuptsova D.G., Radygina T.V., Semikina E.L., Potapov A.S., Fisenko A.P. Age-related changes in the parameters of cellular immunity, the activity of intracellular lymphocyte dehydrogenases and functional activity of neutrophils in children with Gaucher disease. Voprosy gematologii/onkologii i immunopatologii v pediatrii = Pediatric Hematology/Oncology and Immunopathology, 2024, Vol. 23, no. 1, pp. 128-138. (In Russ.)]
- Курбатова О.В., Петричук С.В., Купцова Д.Г., Мовсисян Г.Б., Радыгина Т.В., Комарова А.Д., Анушенко А.О., Фрейдлин Е.В., Семикина Е.Л., Потапов А.С., Фисенко А.П. Активность ядерного фактора транскрипции κB (NF-κB) в популяциях лимфоцитов у детей с болезнью Вильсона–Коновалова // Медицинская иммунология, 2023. Т. 25, № 5. С. 1205-1212. [Kurbatova O.V., Petrichuk S.V., Kuptsova D.G., Movsisyan G.B., Radygina T.V., Komarova A.D., Anushenko A.O., Freidlin E.V., Semikina E.L., Potapov A.S., Fisenko A.P. Nuclear transcription factor κB (NF-κB) activity in lymphocyte populations in children with Wilson–Konovalov disease. Meditsinskaya immunologiya = Medical Immunology (Russia), 2023, Vol. 25, no. 5, pp. 1205-1212. (In Russ.)] doi: 10.15789/1563-0625-NTF-2799.
- Петричук С.В., Радыгина Т.В., Купцова Д.Г., Курбатова О.В., Семикина Е.Л., Мурашкин Н.Н., Потапов А.С., Фисенко А.П. Оценка эффективности анти-tnf терапии у детей с иммунозависимыми заболеваниями по активности NF-κB в популяциях лимфоцитов // Российский иммунологический журнал, 2022. Т. 25, № 4. C. 491-498. [Petrichuk S.V., Radygina T.V., Kuptsova D.G., Kurbatova O.V., Semikina E.L., Murashkin N.N., Potapov A.S., Fisenko A.P. Evaluation of anti-TNF treatment efficiency in children with immune-dependent diseases by means of testing the NF-κB activity in lymphocyte populations. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2022, Vol. 25, no.. 4, pp. 491-498. (In Russ.)] doi: 10.46235/1028-7221-1191-EOA.
- Aflaki E., Moaven N., Borger D.K., Lopez G., Westbroek W., Chae J.J., Marugan J., Patnaik S., Maniwang E., Gonzalez A.N., Sidransky E. Lysosomal storage and impaired autophagy lead to inflammasome activation in Gaucher macrophages. Aging Cell, 2016, Vol. 15, no. 1, pp. 77-88.
- Cox T.M., Drelichman G., Cravo R., Balwani M., Burrow T.A., Martins A.M., Lukina E., Rosenbloom B., Ross L., Angell J., Puga A.C. Eliglustat compared with imiglucerase in patients with Gaucher’s disease type 1 stabilised on enzyme replacement therapy: a phase 3, randomised, open-label, non-inferiority trial. Lancet, 2015, Vol. 385, no. 9985, pp. 2355-2362.
- Grabowski G.A. Phenotype, diagnosis, and treatment of Gaucher’s disease. Lancet, 2008, Vol. 372, no. 9645, pp. 1263-1271.
- Lawrence T. The nuclear factor NF-κB pathway in inflammation. Cold Spring Harb. Perspect. Biol., 2009, Vol. 1, no. 6, a001651. doi: 10.1101/cshperspect.a001651.
- Liu T., Zhang L., Joo D., Sun S.C. NF-κB signaling in inflammation. Signal Transduct. Target. Ther., 2017, Vol. 2, 17023. doi: 10.1038/sigtrans.2017.23.
- Mignot C., Gelot A., Bessières B., Daffos F., Voyer M., Menez F., Fallet Bianco C., Odent S., le Duff D., Loget P., Fargier P., Costil J., Josset P., Roume J., Vanier M.T., Maire I., Billette de Villemeur T. Perinatal-lethal Gaucher disease. Am. J. Med. Genet. A., 2003, Vol. 120A, no. 3, pp. 338-344.
- Pandey M.K., Grabowski G.A. Immunological cells and mediators in Gaucher disease. Blood Cells Mol. Dis., 2018, Vol. 68, pp. 200-205.
- Sen R., Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell, 1986, Vol. 47, no. 6, pp. 921-928.
- Sidransky E. Gaucher disease: insights from a rare Mendelian disorder. Discov Med., 2012, Vol. 14, no. 77, pp. 273-281.
- Şoroğlu C.V., Berkay E.G. Old disease-New reflections: Gaucher, immunity, and inflammation. J. Cell. Mol. Med., 2024, Vol. 28, no. 20, e70087. doi: 10.1111/jcmm.70087.
- Stirnemann J., Belmatoug N., Camou F., Serratrice C., Froissart R., Caillaud C., Levade T., Astudillo L., Serratrice J., Brassier A., Rose C., Billette de Villemeur T., Berger M.G. A review of gaucher disease pathophysiology, clinical presentation and treatments. Int. J. Mol. Sci., 2017, Vol. 18, no. 2, 441. doi: 10.3390/ijms18020441.
- Zahran A.M., Saad K., Elsayh K.I., Abdou M.A.A., Abo-Elgheet A.M., Eloseily E.M., Khalaf S.M., Sror S., Ahmad F.A., Elhoufey A., Ghandour A., Osman N.S. Upregulation of Cytotoxic T-cells in pediatric patients with Gaucher disease. Sci. Rep., 2022, Vol. 12, no. 1, 4977. doi: 10.1038/s41598-022-08843-4.
Supplementary files
