The role of immunological factors in the development of abnormal uterine bleeding in women of reproductive age with extragenital disorders

Authors

DOI:

https://doi.org/10.15587/2519-4798.2022.262184

Keywords:

abnormal uterine bleeding, immune system, antiplatelet autoantibodies, phagocytic reactions, humoral sensitization

Abstract

The aim of the study was to assess the role of immunological factors in the development of abnormal uterine bleeding in women of reproductive age with extragenital disorders.

Materials and methods. The study involved 100 women with abnormal uterine bleeding and accompanying extragenital disorders (main group) and 50 somatically healthy women (control group). Autoimmune antibodies to platelets, phagocytic activity of neutrophil granulocytes, concentration of circulating immune complexes (CICs), total level of membranotropic cytotoxic factors, content of CD4+T-helper subpopulations and cytotoxic CD8+T-killer lymphocytes were evaluated as immunological markers.

Results of the study. The study showed that thrombocytopenia, caused by the presence of autoimmune antibodies to their own platelets, can be one of the pathogenic factors of bleeding in women with AUB. In 41 % of women with AUB, phagocytic reactions were found to be intense, which was expressed by an increase in chemotaxis and adhesion functions, and in 46 % of women by an increase in the absorption capacity of phagocytes. In the main group, 48 % of the examined women had insufficient phagocyte enzymatic activity, which was evidenced by a decrease in the index of completion of phagocytosis. In 79 % of women of the main group, violations of the formation and elimination of circulating immune complexes were detected. The formation of low-molecular-weight CICs in 82 % of women of this cohort contributed to the induction of autoimmune reactions. The total content of membranotropic cytotoxic factors, which was evaluated according to the lymphocytotoxic test, exceeded the reference values in 88 % of women of the main group. In the main group, the average content of CD4+ T-helpers was 23 % lower, and the content of suppressor CD8+ T-lymphocytes was twice as low compared to the control group, resulting in a significant increase in the immunoregulatory index by 30 %.

Conclusion. The women of the main group with abnormal uterine bleeding were found to have a violation of the functional activity of cellular factors of innate immunity, accompanied by changes in the absorption and digestive capacity of phagocytic cells. Assessment of secondary adaptive reactions showed induction of humoral sensitization and formation of autoimmune reactions (presence of antiplatelet autoantibodies, increase in CICs and LCT, decrease in the subpopulation of CD8+-suppressor T-lymphocytes). The detected violations indicate the pathogenic role of immunological reactions in women with abnormal uterine bleeding

Author Biographies

Iryna Tuchkina , Kharkiv National Medical University

Doctor of Medical Sciences, Professor, Head of Department

Department of Obstetrics, Gynecology and Adolescent Gynecology

Roman Blagoveshchensky, Kharkiv National Medical University

Postgraduate Student

Department of Obstetrics, Gynecology and Adolescent Gynecology

References

  1. ACOG committee opinion no. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women (2013). Obstetrics and gynecology, 121 (4), 891–896. doi: http://doi.org/10.1097/01.aog.0000428646.67925.9a
  2. Kazemijaliseh, H., Ramezani Tehrani, F., Behboudi-Gandevani, S., Khalili, D., Hosseinpanah, F., Azizi, F. (2017). A Population-Based Study of the Prevalence of Abnormal Uterine Bleeding and its Related Factors among Iranian Reproductive-Age Women: An Updated Data. Archives of Iranian medicine, 20 (9), 558–563.
  3. Marie, K., Cyrille, N., Etienne, B., Pascal, F. (2020). Epidemiological Profile of Abnormal Uterine Bleeding at the Gyneco-Obstetric and Pediatric Hospital of Yaounde. Open Journal of Obstetrics and Gynecology, 10, 237–242. doi: http://doi.org/10.4236/ojog.2020.1020020
  4. Whitaker, L., Critchley, H. O. (2016). Abnormal uterine bleeding. Best practice & research. Clinical obstetrics & gynaecology, 34, 54–65. doi: http://doi.org/10.1016/j.bpobgyn.2015.11.012
  5. Singh, S., Best, C., Dunn, S., Leyland, N., Wolfman, W. L. et. al. (2013). Abnormal uterine bleeding in pre-menopausal women. Journal of obstetrics and gynaecology Canada, 35 (5), 473–475. doi: http://doi.org/10.1016/s1701-2163(15)30939-7
  6. Iniyaval, R., Jayanthi, B., Lavanya, S., Renuka K. (2021). A Study to Assess the Prevalence and Contributing Factors of Abnormal Uterine Bleeding among Women Admitted in MGMCRI from January to December 2019. Pondicherry Journal of Nursing, 14 (1), 8–10. doi: http://doi.org/10.5005/jp-journals-10084-12173
  7. de Léotoing, L., Chaize, G., Fernandes, J., Toth, D., Descamps, P., Dubernard, G. et. al. (2019). The surgical treatment of idiopathic abnormal uterine bleeding: An analysis of 88 000 patients from the French exhaustive national hospital discharge database from 2009 to 2015. PloS one, 14 (6), e0217579. doi: http://doi.org/10.1371/journal.pone.0217579
  8. Schoep, M. E., Adang, E., Maas, J., De Bie, B., Aarts, J., Nieboer, T. E. (2019). Productivity loss due to menstruation-related symptoms: a nationwide cross-sectional survey among 32 748 women. BMJ open, 9 (6), e026186. doi: http://doi.org/10.1136/bmjopen-2018-026186
  9. Bennett, A., Thavorn, K., Arendas, K., Coyle, D., Singh, S. S. (2020). Outpatient uterine assessment and treatment unit in patients with abnormal uterine bleeding: an economic modelling study. CMAJ open, 8 (4), E810–E818. doi: http://doi.org/10.9778/cmajo.20190170
  10. Hale, K. (2018). Abnormal Uterine Bleeding: A Review. US Pharm, 43 (9), HS2–HS9
  11. Alzahrani, F., Hassan, F. (2019). Modulation of Platelet Functions Assessment during Menstruation and Ovulatory Phases. Journal of medicine and life, 12 (3), 296–300. doi: http://doi.org/10.25122/jml-2019-0005
  12. Dickerson, K. E., Menon, N. M., Zia, A. (2018). Abnormal Uterine Bleeding in Young Women with Blood Disorders. Pediatric clinics of North America, 65 (3), 543–560. doi: http://doi.org/10.1016/j.pcl.2018.02.008
  13. Kristina, M., Lattimore, S., McDavitt, С., Khader, A., Boehnlein, C., Baker-Groberg, S. et. al. (2016). Haley Identification of Qualitative Platelet Disorders in Adolescent Women with Heavy Menstrual Bleeding. Blood, 22 (128), 4922. doi: http://doi.org/10.1182/blood.v128.22.4922.4922
  14. Amesse, L. S., Pfaff-Amesse, T., Gunning, W. T., Duffy, N., French, J. A. (2013). Clinical and laboratory characteristics of adolescents with platelet function disorders and heavy menstrual bleeding. Experimental hematology & oncology, 2 (1), 3. doi: http://doi.org/10.1186/2162-3619-2-3
  15. Critchley, H., Maybin, J. A., Armstrong, G. M., Williams, A. (2020). Physiology of the Endometrium and Regulation of Menstruation. Physiological reviews, 100 (3), 1149–1179. doi: http://doi.org/10.1152/physrev.00031.2019
  16. Alaqzam, T. S., Stanley, A. C., Simpson, P. M., Flood, V. H., Menon, S. (2018). Treatment Modalities in Adolescents Who Present with Heavy Menstrual Bleeding. Journal of pediatric and adolescent gynecology, 31 (5), 451–458. doi: http://doi.org/10.1016/j.jpag.2018.02.130
  17. Schatz, F., Guzeloglu-Kayisli, O., Arlier, S., Kayisli, U. A., Lockwood, C. J. (2016). The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding. Human reproduction update, 22 (4), 497–515. doi: http://doi.org/10.1093/humupd/dmw004
  18. Maybin, J. A., Murray, A. A., Saunders, P., Hirani, N., Carmeliet, P., Critchley, H. (2018). Hypoxia and hypoxia inducible factor-1α are required for normal endometrial repair during menstruation. Nature communications, 9 (1), 295. doi: http://doi.org/10.1038/s41467-017-02375-6
  19. Hapangama, D. K., Bulmer, J. N. (2016). Pathophysiology of heavy menstrual bleeding. Women's health, 12 (1), 3–13. doi: http://doi.org/10.2217/whe.15.81
  20. Critchley, H., Babayev, E., Bulun, S. E., Clark, S., Garcia-Grau, I., Gregersen, P. K. et. al. (2020). Menstruation: science and society. American journal of obstetrics and gynecology, 223 (5), 624–664. doi: http://doi.org/10.1016/j.ajog.2020.06.004
  21. Lee, S. K., Kim, C. J., Kim, D. J., Kang, J. H. (2015). Immune cells in the female reproductive tract. Immune network, 15 (1), 16–26. doi: http://doi.org/10.4110/in.2015.15.1.16
  22. Maybin, J. A., Critchley, H. O. (2015). Menstrual physiology: implications for endometrial pathology and beyond. Human reproduction update, 21 (6), 748–761. doi: http://doi.org/10.1093/humupd/dmv038
  23. Jabbour, H. N., Sales, K. J., Catalano, R. D., Norman, J. E. (2009). Inflammatory pathways in female reproductive health and disease. Reproduction, 138 (6), 903–919. doi: http://doi.org/10.1530/rep-09-0247
  24. Lysenko, O. N., Strizhova, N. V., Kholodova, Z. (2003). Parameters of cellular immunity in perimenopausal patients with glandular and adenomatous endometrial hyperplasia. Bulletin of experimental biology and medicine, 135 (1), 77–80. doi: http://doi.org/10.1023/a:1023410332246
  25. Fraser, I. S., Mansour, D., Breymann, C., Hoffman, C., Mezzacasa, A., Petraglia, F. (2015). Prevalence of heavy menstrual bleeding and experiences of affected women in a European patient survey. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 128 (3), 196–200. doi: http://doi.org/10.1016/j.ijgo.2014.09.027
  26. Rodeghiero, F., Marranconi, E. (2020). Management of immune thrombocytopenia in women: current standards and special considerations. Expert Review of Hematology, 13 (2), 175–185. doi: http://doi.org/10.1080/17474086.2020.1711729
  27. van Dijk, W., Punt, M. C., van Galen, K., van Leeuwen, J., Lely, A. T., Schutgens, R. (2022). Menstrual problems in chronic immune thrombocytopenia: A monthly challenge – a cohort study and review. British journal of haematology, 10. doi: https://doi.org/10.1111/bjh.18291
  28. Cooper, N., Kruse, A., Kruse, C., Watson, S., Bussel, J. B. (2021). Immune thrombocytopenia (ITP) World Impact Survey (iWISh): Patient and physician perceptions of diagnosis, signs and symptoms, and treatment. American journal of hematology, 96 (2), 188–198. doi: http://doi.org/10.1002/ajh.26045
  29. Burbano, C., Villar-Vesga, J., Vásquez, G., Muñoz-Vahos, C., Rojas, M., Castaño, D. (2019). Proinflammatory Differentiation of Macrophages Through Microparticles That Form Immune Complexes Leads to T- and B-Cell Activation in Systemic Autoimmune Diseases. Frontiers in immunology, 10, 2058. doi: http://doi.org/10.3389/fimmu.2019.02058
  30. McInnes, I. B., Schett, G. (2011). The pathogenesis of rheumatoid arthriis. The New England journal of medicine, 365 (23), 2205–2219. doi: http://doi.org/10.1056/nejmra1004965
  31. Burbano, C., Villar-Vesga, J., Orejuela, J., Muñoz, C., Vanegas, A., Vásquez, G., Rojas, M., Castaño, D. (2018). Potential Involvement of Platelet-Derived Microparticles and Microparticles Forming Immune Complexes during Monocyte Activation in Patients with Systemic Lupus Erythematosus. Frontiers in immunology, 9, 322. doi: http://doi.org/10.3389/fimmu.2018.00322
  32. Burbano, C., Rojas, M., Vásquez, G., Castaño, D. (2015). Microparticles That Form Immune Complexes as Modulatory Structures in Autoimmune Responses. Mediators of inflammation, 2015. doi: http://doi.org/10.1155/2015/267590
  33. Mayadas, T. N., Tsokos, G. C., Tsuboi, N. (2009). Mechanisms of immune complex-mediated neutrophil recruitment and tissue injury. Circulation, 120 (20), 2012–2024. doi: http://doi.org/10.1161/circulationaha.108.771170
  34. Thurman, J. M., Yapa, R. (2019). Complement Therapeutics in Autoimmune Disease. Frontiers in immunology, 10, 672. doi: http://doi.org/10.3389/fimmu.2019.00672
  35. Kaul, A., Gordon, C., Crow, M. K., Touma, Z., Urowitz, M. B., Ruiz-Irastorza, G. et. al. (2016). Systemic lupus erythematosus. Nature Reviews Disease Primers, 2 (1). doi: http://doi.org/10.1038/nrdp.2016.39
  36. Yan, M., Marsters, S. A., Grewal, I. S., Wang, H., Ashkenazi, A., Dixit, V. M. (2000). Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity. Nature immunology, 1 (1), 37–41. doi: http://doi.org/10.1038/76889
  37. Lai, Z. Z., Ruan, L. Y., Wang, Y., Yang, H. L., Shi, J. W., Wu, J. N. et. al. (2020). Changes in subsets of immunocytes in endometrial hyperplasia. American journal of reproductive immunology, 84 (4), e13295. doi: http://doi.org/10.1111/aji.13295
  38. Witkiewicz, A. K., McConnell, T., Potoczek, M., Emmons, R. V., Kurman, R. J. (2010). Increased natural killer cells and decreased regulatory T cells are seen in complex atypical endometrial hyperplasia and well-differentiated carcinoma treated with progestins. Human pathology, 41 (1), 26–32. doi: http://doi.org/10.1016/j.humpath.2009.06.012

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Published

2022-07-29

How to Cite

Tuchkina , I., & Blagoveshchensky, R. (2022). The role of immunological factors in the development of abnormal uterine bleeding in women of reproductive age with extragenital disorders. ScienceRise: Medical Science, (4(49), 4–10. https://doi.org/10.15587/2519-4798.2022.262184

Issue

No. 4(49) (2022)

Section

Medical Science

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Copyright (c) 2022 Iryna Tuchkina , Roman Blagoveshchensky

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