Features of the subpopulation composition and functional activity of peripheral blood lymphocytes and monocytes in patients with primary autoimmune thrombocytopenia
https://doi.org/10.17650/1818-8346-2025-20-3-76-83
Abstract
Background. Primary immune thrombocytopenia (ITP) is an immune-mediated disease characterized by platelet destruction and impaired thrombopoiesis with the development of varying severity hemorrhagic syndrome. The first line of therapy for ITP patients are glucocorticosteroids, which have limited efficacy and frequent complications. Factors of innate and adaptive immunity play a key role in ITP pathogenesis, the study of which is especially relevant for assessing the immunological reactivity of patients and substantiating new therapeutic approaches in real clinical practice.
Aim. To evaluate the characteristics of the subpopulation composition and functional activity of peripheral blood lymphocytes and monocytes in ITP patients and to identify possible immunological prognostic criteria for the disease course and resistance to glucocorticosteroid therapy.
Materials and methods. In 20 patients with newly diagnosed ITP and in 20 ITP patients with resistance to glucocorticosteroid therapy, the relative and absolute parameters of T-lymphocytes (CD3+), B-lymphocytes (CD19+), NK cells (CD3–CD16+CD56+), T-helper cells (CD3+CD4+), T-cytotoxic (CD3+CD8+) and NKT (CD3+CD16+CD56+) subpopulations of peripheral blood lymphocytes, as well as the expression of HLA-DR on lymphocytes and monocytes, CD25 on CD4+ T-lymphocytes and CD40 on B -lymphocytes were analyzed using flow cytometry. Thirty healthy individuals were examined as a control group.
Results. In patients with newly diagnosed ITP, a sharp decrease in the absolute number of B cells and T-helper lymphocytes in peripheral blood was observed, and pronounced activation of T-lymphocytes by HLA-DR expression and B-lymphocytes by costimulatory molecule CD40 expression was noted. In patients with glucocorticosteroids resistance, a significant decrease in the absolute number of peripheral blood T-helper lymphocytes, an increase in the content of activated CD3+HLA-DR+ lymphocytes were also detected, but the level of CD40+ B-lymphocytes was reduced compared to primary patients.
In patients of both groups, a significant (p <0.001) decrease in HLA-DR mean fluorescence intensity on peripheral blood monocytes was detected, which may indicate an insufficient ability of monocytes and macrophages to effectively antigen processing.
Conclusion. Patients with ITP have been found to have significant disturbances in the quantitative parameters of cellular adaptive immunity and the functional activity of peripheral blood lymphocytes and monocytes, which play an important role in the immunopathogenesis of the disease.
About the Authors
Yu. Yu. ChuksinaRussian Federation
Yulia Yuryevna Chuksina
61 / 2 Shchepkina St., Moscow 129110
S. G. Zakharov
Russian Federation
61 / 2 Shchepkina St., Moscow 129110
T. A. Mitina
Russian Federation
61 / 2 Shchepkina St., Moscow 129110
References
1. Clinical recommendations. Idiopathic thrombocytopenic purpura (ITP) in adults. 2021. Available at: https://cr.minzdrav.gov.ru/schema/150_2 (accessed 04.02.2024). (In Russ.).
2. Kovaleva L.G., Pustovaya E.I., Safonova T.I. Idiopathic thrombocytopenic purpura (ITP) of adults. Primary immune thrombocytopenia (ITP) in adults. Werlhof’s disease. Moscow: Gematologicheskiy nauchniy tsentr, 2014. 131 p. (In Russ.).
3. Provan D., Arnold D., Bussel J.B. et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 2019;3(22):3780–808. DOI: 10.1182/bloodadvances-2019000812
4. Zhao C., Li X., Zhang F. et al. Increased cytotoxic T-lymphocytemediated cytotoxicity predominant in patients with idiopathic thrombocytopenic purpura without platelet autoantibodies. Haematologica 2008;93(9):1428–30. DOI: 10.3324/haematol.12889
5. Cines D.B., Cuker A., Semple J.W. Pathogenesis of immune thrombocytopenia. Presse Med 2014;43(4 Pt 2):e49–59. DOI: 10.1016/j.lpm.2014.01.010
6. Ogawara H., Handa H., Morita K. et al. High Th1/Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura. Eur J Haematol 2003;71(4):283–8. DOI: 10.1034/j.1600-0609.2003. 00138.x
7. Wang T., Zhao H., Ren H. et al. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica 2005;90(7):914–23.
8. Guo Z.X., Chen Z.P., Zheng C.L. et al. The role of Th17 cells in adult patients with chronic idiopathic thrombocytopenic purpura. Eur J Haematol 2009;82(6):488–9. DOI: 10.1111/j.1600-0609.2009.01229.x
9. Zhang J., Ma D., Zhu X. et al. Elevated profile of Th17, Th1 and Tc1 cells in patients with immune thrombocytopenic purpura. Haematologica 2009;94(9):1326–9. DOI: 10.3324/haematol.2009.007823
10. Cao J., Chen C., Zeng L. et al. Elevated plasma IL-22 levels correlated with Th1 and Th22 cells in patients with immune thrombocytopenia. Clin Immunol 2011;141(1):121–3. DOI: 10.1016/j.clim.2011. 05.003
11. Hu Y., Li H., Zhang L. et al. Elevated profiles of Th22 cells and correlations with Th17 cells in patients with immune thrombocytopenia. Hum Immunol 2012;73(6):629–35. DOI: 10.1016/j.humimm.2012. 04.015
12. Audia S., Rossato M., Santegoets K. et al. Splenic TFH expansion participates in B-cell differentiation and antiplate-let-antibody production during immune thrombocytopenia. Blood 2014;124(18):2858–66. DOI: 10.1182/blood-2014-03-563445
13. Zhong H., Bao W., Li X. et al. CD16+ monocytes control T-cell subset development in immune thrombocytopenia. Blood 2012;120(16):3326–35. DOI: 10.1182/blood-2012-06-434605
14. Semple J.W., Bruce S., Freedman J. Suppressed natural killer cell activity in patients with chronic autoimmune thrombocytopenic purpura. Am J Hematol 1991;37(4):258–62. DOI: 10.1002/ajh.2830370409
15. Garcia-Suarez J., Prieto A., Reyes E. et al. Severe chronic autoimmune thrombocytopenic purpura is associated with an expansion of CD56+CD3– natural killer cells subset. Blood 1993;82(5):1538–45.
16. Ebbo M., Audonnet S., Grados A. et al. NK cell compartment in the peripheral blood and spleen in adult patients with primary immune thrombocytopenia. Clin Immunol 2017;177:18–28. DOI: 10.1016/j.clim.2015.11.005
17. Olsson B., Andersson P.O., Jernas M. et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 2003;9(9):1123–4. DOI: 10.1038/nm921
18. Kuter D.J. The treatment of immune thrombocytopenia (ITP) – focus on thrombopoietin receptor agonists. Ann Blood 2021;6(7):1–21. DOI: 10.21037/aob-21-23
19. Zufferey A., Kapur R., Semple J.W. Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP). J Clin Med 2017;6(2):16. DOI: 10.3390/jcm6020016
20. Zakharov S.G., Mitina T.A., Zakharova A.V. et al. Glucocorticosteroid-induced complications in patients with idiopathic thrombocytopenic purpura. Onkogematologiya = Oncohematology 2023;18(4):233–43. (In Russ.). DOI: 10.17650/1818‑8346‑2023‑18‑4‑233‑243
21. Yadgarov M.Ya., Kuzovlev A.N., Berikashvili L.B. et al. Importance of data distribution normality test: theory and practical guide. Anesteziologiya i reanimatologiya = Russian Journal of Anaesthesiology and Reanimatology 2021;(2):136–42. (In Russ.). DOI: 10.17116/anaesthesiology2021021136
22. Ярилин А.А. Иммунология. М.: ГЭОТАР-Медиа, 2010. С. 452 Yarilin A.A. Immunology. Moscow: GEOTAR-Media, 2010. P. 452. (In Russ.).
23. Grewal I.S., Flavell R.A. CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol 1998;16:111–35. DOI: 10.1146/annurev.immunol.16.1.111
24. Koupenova M., Clancy L., Corkrey H.A., Freedman J.E. Circulating platelets as mediators of immunity, inflammation, and thrombosis. Circ Res 2018;122(2):337–51. DOI: 10.1161/CIRCRESAHA.117.310795
25. Frelinger A.L. 3rd, Grace R.F., Gerrits A.J. et al. Platelet function tests, independent of platelet count, are associated with bleeding severity in ITP. Blood 2015;126(7):873–9. DOI: 10.1182/ blood-2015-02-628461
26. Kuwana M., Nomura S., Fujimura K. et al. Effect of a single injection of humanized anti-CD154 monoclonal antibody on the platelet-specific autoimmune response in patients with immune thrombocytopenic purpura. Blood 2004;103(4):1229–36. DOI: 10.1182/ blood-2003-06-2167
27. Kuwana M., Kawakami Y., Ikeda Y. Suppression of autoreactive T-cell response to glycoprotein IIb/IIIa by blockade of CD40/CD154 interaction: implications for treatment of immune thrombocytopenic purpura. Blood 2003;101(2):621–3. DOI: 10.1182/blood-2002-07-2157
28. Chuksina Yu.Yu., Zakharov S.G., Mitina T.A., Khmelevskaya A.N. Clinical and prognostic significance of T-regulatory cells and CD28 expression on T-lymphocytes in patients with immune thrombocytopenia. Onkogematologiya = Oncohematology 2024;19(4):108–14. (In Russ.). DOI: 10.17650/1818-8346-2024-19-4-108-114
29. Khaidukov S.V., Zurochka A.V., Chereshnev V.A. Cytometric analysis in clinical immunology. Ekaterinburg: Ural Branch of the Russian Academy of Sciences, 2011. Vol. 4. P. 220. (In Russ.).
30. Klochkova-Abelyants S.A., Surzhikova G.S. Expression of HLA-DR antigens on peripheral blood monocytes as an indicator of the state of the immune system in hypochromic anemia. Politravma = Polytrauma 2012;2:59–67. (In Russ.).
31. Zurochka A.V., Kotlyarov A.N., Kuvaytsev M.V. et al. Changes of HLA-DR antigen expression on monocytes in children and their clinical significance in sepsis. Meditsinskaya immunologiya = Medical Immunology (Russia) 2008;10(4–5):379–87. (In Russ.). DOI: 10.15789/1563-0625-2008-4-5-379-388
32. Strohmeyer J.C., Blume C., Meisel C. et al. Standardized immune monitoring for the prediction of infections after cardiopulmonary bypass surgery in risk patients. Cytometry 2003;53(1):54–62. DOI: 10.1002/cyto.b.10031
33. Hoffman J.A., Weinberg K.I., Azen C.G. et al. Human leukocyte antigen-DR expression on peripheral blood monocytes and the risk of pneumonia in pediatric lung transplant recipients. Transpl Infect Dis 2004;6(4):147–55. DOI: 10.1111/j.1399-3062.2004.00069.x
34. Chuksina Yu.Yu., Moskalets O.V., Yazdovsky V.V. et al. Clinical and immunological parallels in periprosthetic infection after total large joints arthroplasty. Kazanskiy meditsinskiy zhurnal = Kazan Medical Journal 2016;97(4):514–8. (In Russ.). DOI: 10.17750/KMJ2016-514
Review
For citations:
Chuksina Yu.Yu., Zakharov S.G., Mitina T.A. Features of the subpopulation composition and functional activity of peripheral blood lymphocytes and monocytes in patients with primary autoimmune thrombocytopenia. Oncohematology. 2025;20(3):76-83. (In Russ.) https://doi.org/10.17650/1818-8346-2025-20-3-76-83