Single article

DOI: 10.47026/2413-4864-2024-1-10-18

Kudryashov S.I., Stenina M.A., Karzakova L.M., Autonomova O.I., Grigorieva I.M., Shestipalova M.V.

Features of the T-Immune System in Patients with Glomerulonephritises with Nephrotic Syndrome

Keywords: glomerulonephritis, nephrotic syndrome, T-lymphocytes, T-regulatory cells, T-cell subset

The study of issues related to glomerulonephritises with nephrotic syndrome is one of the urgent problems of medicine due to their prevalence worldwide, mainly in the young age group. Medical workers distinguish primary (idiopathic) nephrotic syndrome, which occurs in 80–90% of cases, and secondary nephrotic syndrome, mainly associated with systemic autoimmune diseases, diabetes mellitus and neoplasms. Glomerulonephritises, manifested by nephrotic syndrome (membranous nephropathy, focal segmental glomerulosclerosis, nephropathy with minimal changes), are known to be autoimmune diseases. To date, the immunological mechanisms of the pathogenesis of glomerulonephritises with nephrotic syndrome associated with the T-system of adaptive immunity remain unexplored. The aim of the study was to study the role of the T–immune system in the pathogenesis of primary nephrotic syndrome based on the study of immunoregulatory, activated T-cell subsets in patients with this pathology. Material and methods. 136 patients with chronic glomerulonephritis with nephrotic syndrome were selected for the study. The assessment of the T-immune system included determination of the lymphocyte phenotype of immunoregulatory T-cell subsets (T-helper/inducers, cytotoxic T-lymphocytes), various subpopulations of activated T-cells (activated T-lymphocytes; activated T-lymphocytes expressing CD25–alpha chain of IL-2 receptor; activated cytotoxic T-lymphocytes expressing HLA-DR and CD38) and regulatory T-cells (Treg cells). Study results. In the patients of the examined cohort, an increase in the number of T-lymphocytes and T-helper cells, as well as activated T-lymphocytes expressing HLA-DR antigens, was found. At this, the content of cytotoxic T-cells and the number of activated T-cells expressing the IL-2 – CD25 receptor did not differ from similar indicators in healthy individuals. The levels of Treg cells and activated cytotoxic T-lymphocytes with the CD3+CD8brightCD38+ phenotype were reduced. The immunoregulatory index (T-helpers/cytotoxic T-lymphocytes) was increased, due to an increase in the number of T-helper cells against the background of an unchanged number of cytotoxic T-lymphocytes. Conclusions. The results of the study indicate that the main features of the T-system of the immune response in primary nephrotic syndrome are imbalance in the ratio of the content of immunoregulatory cells due to predominance of T-helper cells and a decrease in the number of Treg cells.

References

  1. Bajnok A., Ivanova M., Rigo J., Jr., Toldi G.The Distribution of Activation Markers and Selectins on Peripheral T Lymphocytes in Preeclampsia. Mediators Inflamm., 2017, 2017, e8045161. DOI: 10.1155/2017/8045161.
  2. Boumediene A., Vachin P., Sendeyo K. et al. NEPHRUTIX: A randomized, double-blind, placebo vs. Rituximab-controlled trial assessing T-cell subset changes in Minimal Change Nephrotic Syndrome. Autoimmun., 2018, vol. 88, pp. 91–102. DOI: 10.1016/j.jaut.2017.10.006.
  3. Campbell R.E., Thurman J.M. The Immune System and Idiopathic Nephrotic Syndrome. J. Am. Soc. Nephrol., 2022, vol. 17, pp. 1823–1834. DOI: 10.2215/CJN.07180622.
  4. Chen M., Liu J., Xiong Y., Xu G. Treatment of Idiopathic Membranous Nephropathy for Moderate or Severe Proteinuria: A Systematic Review and Network Meta-Analysis.  J. Clin. Pract., 2022, vol. 2022, e4996239. DOI: 10.1155/2022/4996239.
  5. Colucci M., Oniszczuk J., Vivarelli M., Audard V. B-Cell Dysregulation in Idiopathic Nephrotic Syndrome: What We Know and What We Need to Discover. Immunol., 2022, vol. 13, e823204. DOI: 10.3389/fimmu.2022.823204.
  6. Dall’Era M., Pauli M.L, Remedios K. et al. Autoimmunity Centers of Excellence. Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus. Arthritis Rheumatol., 2019, vol. 71(3), pp. 431–440. DOI: 10.1002/art.40737.
  7. Fervenza F.C., Appel G.B., Barbour S.J. et al. Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. Engl. J. Med., 2019, vol. 381(1), pp. 36–46. DOI: 10.1056/NEJMoa1814427.
  8. Go A.S., Tan T.C., Chertow G.M. et al. Primary nephrotic syndrome and risks of ESKD, cardiovascular events, and death: the Kaiser Permanente nephrotic syndrome study. Am. Soc. Nephrol., 2021, vol. 32, pp. 2303–2314. DOI: 10.1681/ASN.2020111583.
  9. Hu R., Quan S., Wang Y. et al. Spectrum of biopsy proven renal diseases in central China: A 10-year retrospective study based on 34,630 cases. Rep., 2020, vol. 10, e10994. DOI: 10.1038/s41598-020-67910-w.
  10. Jarnicki A.G., Lysaght J., Todryk S., Mills K.H. Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells. Immunol., 2006, vol. 177(2), pp. 896–904. DOI: 10.4049/jimmunol.177.2.896.
  11. Kemper M.J., Zepf K., Klaassen I. et al. Changes of lymphocyte populations in pediatric steroid-sensitive nephrotic syndrome are more pronounced in remission than in relapse. Am J. Nephrol., 2005, vol. 25(2), pp. 132–137. DOI: 10.1159/000085357.
  12. Khandelwal P., Chaturvedi V., Owsley E. et al. CD38brightCD8+ T Cells Associated with the Development of Acute GVHD Are Activated, Proliferating, and Cytotoxic Trafficking Cells.  Blood Marrow Transplant., 2020, vol. 26(1), pp. 1–6. DOI: 10.1016/j.bbmt.2019.08.008.
  13. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int., 2021, vol. 100(4S), S1– DOI: 10.1016/j.kint.2021.05.021.
  14. Kumar P., Saini S., Khan S. et al. Restoring self-tolerance in autoimmune diseases by enhancing regulatory T-cells. Cell Immunol., 2019, vol. 339, pp. 41–49. DOI: 10.1016/j.cellimm.2018.09.008.
  15. Kuroki A., Iyoda M., Shibata T., Sugisaki T. Th2 cytokines increase and stimulate B cells to produce IgG4 in idiopathic membranous nephropathy. Kidney Int., 2005, vol. 68(1), pp. 302– DOI: 10.1111/j.1523-1755.2005.00415.x.
  16. Lama G., Luongo I., Tirino G. et al. T-lymphocyte populations and cytokines in childhood nephrotic syndrome. J. Kidney Dis., 2002, vol. 39(5), pp. 958–965. DOI: 10.1053/ajkd.2002.32769.
  17. Ma D.H., Yang X.D., Hua Q.J. et al. Changes and significance of Treg and Th17 in adult patients with primary membranous nephropathy. Nephrol., 2021, vol. 96(3), pp. 155–164. DOI: 10.5414/CN110333.
  18. Motavalli R., Etemadi J., Kahroba H. et al. Immune system-mediated cellular and molecular mechanisms in idiopathic membranous nephropathy pathogenesis and possible therapeutic targets. Life Sci., 2019, vol. 238, e116923. DOI: 10.1016/j.lfs.2019.116923.
  19. Motavalli R., Etemadi J., Soltani-Zangbar M.S. et al. Altered Th17/Treg ratio as a possible mechanism in pathogenesis of idiopathic membranous nephropathy. Cytokine, 2021, vol. 141, e155452. DOI: 10.1016/j.cyto.2021.155452.
  20. Pal A., Kaskel F. History of nephrotic syndrome and evolution of its treatment. Pediatr., 2016, vol. 4, p. 56. DOI: 10.3389/fped.2016.00056.
  21. Piedra-Quintero Z.L., Wilson Z., Nava P., Guerau-de-Arellano M. CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity. Immunol., 2020, vol. 30(11), e597959. DOI: 10.3389/fimmu.2020.597959.
  22. Ponticelli C., Praga M., Moroni G. Calcineurin Inhibitors in Membranous Nephropathy. Kidney Int. Rep., 2021, vol. 6(10), pp. 2537– DOI: 10.1016/j.ekir.2021.08.008.
  23. Primary nephrotic syndrome in children: Clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A Report of the International Study of Kidney Disease in Children. Kidney Int., 1981, vol. 20, pp. 765–771. DOI: 10.1038/ki.1981.209.
  24. Richards N.T., Darby S., Howie A.J. et al. Knowledge of renal histology alters patient management in over 40% of cases. Dial. Transplant., 1994, vol. 9(9), pp. 1255–1259.
  25. Sakaguchi S. Taking regulatory T cells into medicine. Exp. Med., 2021, vol. 218(6), e20210831. DOI: 10.1084/jem.20210831.
  26. Salfi G., Casiraghi F., Remuzzi G. Current understanding of the molecular mechanisms of circulating permeability factor in focal segmental glomerulosclerosis.  Immunol., 2023, vol.14, e1247606. DOI: 10.3389/fimmu.2023.1247606.
  27. So L., Obata-Ninomiya K., Hu A. et al. Regulatory T cells suppress CD4+ effector T cell activation by controlling protein synthesis. Exp. Med., 2023, vol. 220(3), e20221676. DOI: 10.1084/jem.20221676.
  28. Tsuji S., Akagawa S., Akagawa Y. et al. Idiopathic nephrotic syndrome in children: role of regulatory T cells and gut microbiota. Res., 2021, vol. 89(5), pp. 1185–1191. DOI: 10.1038/s41390-020-1022-3.
  29. Vivarelli M., Massella L., Ruggiero B., Emma F. Minimal change disease. J. Am. Soc. Nephrol, 2017, vol. 12, pp. 332–345. DOI: 10.2215/CJN.05000516.

About authors

Kudryashov Sergei I.
Candidate of Medical Sciences, Associate Professor, Department of Internal Diseases, Chuvash State University, Russia, Cheboksary (medicpro21@mail.ru; ORCID: https://orcid.org/0000-0003-2277-9425)
Stenina Marina A.
Doctor of Medical Sciences, Professor, Department of Immunology, N.I. Pirogov Russian National Research Medical University, Russia, Moscow (stenina_ma@mail.ru; ORCID: https://orcid.org/0009-0007-0488-9598)
Karzakova Luiza M.
Doctor of Medical Sciences, Professor, Head of Internal Diseases Department, Chuvash State University, Russia, Cheboksary (luizak58@mail.ru; ORCID: https://orcid.org/0000-0002-5899-6352)
Grigorieva Irina M.
Nephrologist, Nephrological Department, Republican Clinical Hospital, Russia, Cheboksary (sim003@yandex.ru; ORCID: https://orcid.org/0009-0002-3512-5295)
Autonomova Olga I.
Candidate of Medical Sciences, Chief Physician, Fresenius Nephroke Dialysis Center, Russia, Novocheboksarsk (olga-aoi@yandex.ru; ORCID: https://orcid.org/0000-0001-9259-2661)
Shestipalova Maria V.
Head of the Laboratory, Centralized Diagnostic Laboratory «Hemohelp» («ABK-Med»), Russia, Nizhny Novgorod (zavlab@gemohelp.ru; ORCID: https://orcid.org/0009-0004-5508-4069)

Article link

Kudryashov S.I., Stenina M.A., Karzakova L.M., Autonomova O.I., Grigorieva I.M., Shestipalova M.V. Features of the T-Immune System in Patients with Glomerulonephritises with Nephrotic Syndrome [Electronic resource] // Acta medica Eurasica. – 2024. – №1. P. 10-18. – URL: https://acta-medica-eurasica.ru/en/single/2024/1/2/. DOI: 10.47026/2413-4864-2024-1-10-18.