Phenotypic characterization of peripheral blood innate immune cell subpopulations in women with endometriosis before and after surgery


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Abstract

Objective: To investigate phenotypic characteristics of innate immune cell subpopulations in women with endometriosis before and after combination therapy, including surgery. Materials and methods: The study included women with stage I-II (n=12) and III-IV(n=28) endometriosis, who underwent clinical and immunological investigations before and after combination therapy, including surgery. Peritoneal fluid samples obtained intraoperatively and blood samples drawn from the study subjects before and six months after surgery were phenotyped for mononuclear cells using flow cytometry (n=15). Results: In the peritoneal fluid of women with endometriosis, the proportions of TCRyd cells (p<0.001) and T regulatory cells with the CD4+CD25+CD127low/- phenotype (Treg cells) (p=0.028) were lower than in controls. Compared with peripheral blood, there was a decrease in the proportion of cytotoxic CD3-CD56+CD16+-NK cells (p<0.001), an increase in the proportion of regulatory CD56bnghtCD16dim-NK cells (p=0.005). Compared to the control, the proportion of Treg cells in peripheral blood was also reduced (p=0.028). Besides, the neutrophil-lymphocyte index (p=0.022) was increased. There was a reduction in the proportion of CD14highCD16low -classical monocytes (p=0.017), while the proportion of non-classical was increased (p= 0.009). Six months after surgery, the total leukocyte count, neutrophil-lymphocyte index, and the proportion of Treg cells in the peripheral blood significantly differ from the baseline values (p=0.008, p=0.017, and p=0.001, respectively), not differing from the control values. Conclusion: The imbalance between regulatory and cytotoxic subpopulations is more pronounced at the local than at the systemic level. Nevertheless, after combination therapy, including surgery, there was a noticeable tendency towards normalization of the altered peripheral blood parameters against the background of an improvement in clinical symptoms, particularly in relieving the pain.

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About the authors

Tatiana D. Korotkova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: t_korotkova@oparina4.ru
Obstetrician-Gynecologist, PhD. Student at the Department of Gynecology

Lubov V. Krechetova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: l_krechetova@oparina4.ru
Dr. Med. Sci., Head of the Laboratory of Clinical Immunology

Eugenia V. Inviyaeva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: e_inviyaeva@oparina4.ru
Ph.D. (bio.sci.), Senior Researcher at the Laboratory of Clinical Immunology

Valentina V. Vtorushina

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: v_vtorushina@oparina4.ru
Ph.D., Immunologist at the Laboratory of Clinical Immunology

Ludmila V. Vanko

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: lvanko@oparina4.ru
Dr. Med. Sci., Professor, Leading Researcher at the Laboratory of Clinical Immunology

Leyla V. Adamyan

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: adamyanleila@gmail.com
Dr. Med. Sci., Academician of the RAS, Professor, Head of the Department of Gynecology, Deputy Director for Science

References

  1. Rafique S., DeCherney A.H. Medical management of endometriosis. Clin. Obstet. Gynecol. 2017; 60(3): 485-96. https://dx.doi.org/10.1097/GRF.0000000000000292.
  2. Адамян Л.В., Андреева Е.Н. Роль современной гормономодулирующей терапии в комплексном лечении генитального эндометриоза. Проблемы репродукции. 2011; 17(6): 66-77.
  3. Burney R.O., Giudice L.C. Pathogenesis and pathophysiology of endometriosis. Fertil. Steril. 2012; 98(3): 511-9. https://dx.doi.org/10.1016/j.fertnstert.2012.06.029.
  4. Lagana A.S., Garzon S., Gotte M., Vigano P., Franchi M., Ghezzi F. et al. The pathogenesis of endometriosis: molecular and cell biology insights. Int. J. Mol. Sci. 2019; 20(22): 5615. https://dx.doi.org/10.3390/ijms20225615.
  5. Анциферова Ю.С., Сотникова Н.Ю., Назаров С.Б. Иммунные механизмы развития генитального эндометриоза. Иваново; 2007. 312с.
  6. Ярмолинская М.И. Цитокиновый профиль перитонеальной жидкости и периферической крови больных с наружным генитальным эндометриозом. Журнал акушерства и женских болезней. 2008; 57(3): 30-4.
  7. Jeung I., Cheon K., Kim M.R. Decreased cytotoxicity of peripheral and peritoneal natural killer cell in endometriosis. Biomed. Res. Int. 2016; 2016: 2916070. https://dx.doi.org/10.1155/2016/2916070.
  8. Xu H., Zhao J., Lu J., Sun X. Ovarian endometrioma infiltrating neutrophils orchestrate immunosuppressive microenvironment. J. Ovarian Res. 2020; 13(1): 44. https://dx.doi.org/10.1186/s13048-020-00642-7
  9. Kang Y.-J., Jeung I.C., Park A., Park Y.J., Jung H., Kim T.D. et al. An increased level of IL-6 suppresses NK cell activity in peritoneal fluid of patients with endometriosis via regulation of SHP-2 expression. Hum. Reprod. 2014; 29(10): 2176-89. https://dx.doi.org/10.1093/humrep/deu172.
  10. Michel T., Poli A., Cuapio A., Briquemont B., Iserentant G., Ollert M. et al. Human CD56bright NK cells: an update. J. Immunol. 2016; 196(7): 2923-31. https://dx.doi.org/10.4049/jimmunol.1502570.
  11. Fu B., Tian Z., Wei H. Subsets of human natural killer cells and their regulatory effects. Immunology. 2014; 141(4): 483-9. https://dx.doi.org/10.1111/imm.12224.
  12. Ming B., Wu T., Cai S., Hu P., Tang J., Zheng F. et al. The increased ratio of blood CD56 bright NK to CD56 dim NK is a distinguishing feature of primary Sjogren's syndrome. J. Immunol. Res. 2020; 2020: 7523914. https://dx.doi.org/10.1155/2020/7523914.
  13. Ginhoux F., Jung S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat. Rev. Immunol. 2014; 14(6): 392-404. https://dx.doi.org/10.1038/nri3671.
  14. Geissmann F., Manz M.G., Jung S., Sieweke M.H., Merad M., Ley K. Development of monocytes, macrophages, and dendritic cells. Science. 2010; 327(5966): 656 61. https://dx.doi.org/10.1126/science.1178331
  15. Eljaszewicz A., Wiese M., Helmin-Basa A., Jankowski M., Gackowska L., Kubiszewska I. et al. Collaborating with the enemy: function of macrophages in the development of neoplastic disease. Mediators Inflamm. 2013; 2013: 831387. https://dx.doi.org/10.1155/2013/831387.
  16. Hogg С., Horne A. W., Erin C. Endometriosis-associated macrophages: origin, phenotype, and function. Front. Endocrinol. (Lausanne). 2020; 11: 7. https://dx.doi.org/10.3389/fendo.2020.00007.
  17. Wong K.L., Yeap W.H., Tai J.J., Ong S.M., Dang T.M., Wong S.C. The three human monocyte subsets: implications for health and disease. Immunol. Res. 2012; 53(1-3): 41-57. https://dx.doi.org/10.1007/s12026-012-8297-3.
  18. Prat M., Naour A.L., Coulson K., Lemee F., Leray H., Jacquemin G. et al. Circulating CD14high CD16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression. J. Immunother. Cancer. 2020; 8(1): e000472. https://dx.doi.org/10.1136/jitc-2019-000472.
  19. Gogacz M., Winkler I., Bojarska-Junak A., Tabarkiewicz J., Semczuk A., Rechberger T. et al. Increased percentage of Th17 cells in peritoneal fluid is associated with severity of endometriosis. J. Reprod. Immunol. 2016; 117: 39-44. https://dx.doi.org/10.1016/j.jri.2016.04.289.
  20. Kim S.K., Park J.Y., Jee B.C., Suh C.S., Kim S.H. Association of the neutrophil-to-lymphocyte ratio and CA 125 with the endometriosis score. Clin. Exp. Reprod. Med. 2014; 41(4): 151. https://dx.doi.org/10.5653/cerm.2014.4L4.151.
  21. Yang H., Lang J., Zhu L., Wang S., Sha G., Zhang Y. Diagnostic value of the neutrophil-to-lymphocyte ratio and the combination of serum CA-125 for stages III and IV endometriosis. Chin. Med. J. (Engl). 2013; 126(11): 2011-4.
  22. Сельков С.А., Ярмолинская М.И. Эндометриоз как патология регуляторных механизмов. Журнал акушерства и женских болезней. 2017; 66(2): 9-13. [Selkov S.A., Yarmolinskaya M.I. Endometriosis as a pathology of regulatory mechanisms. Journal of Obstetrics and Women's Diseases. 2017; 66(2): 9-13. (in Russian)]. https://dx.doi.org/10.17816/J0WD6629-13.
  23. Калашникова А. А., Ворошилова Т. М., Чиненое а Л. В., Давыдова Н.И., Калинина Н.М. Субпопуляции моноцитов у здоровых лиц и у пациентов с сепсисом. Медицинская иммунология. 2018; 20(6): 815-24. https://doi.org/10.15789/1563-0625-2018-6-815-824.
  24. Инвияева Е.В., Короткова Т.Д., Вт ору шин а В. В., Кречетов а Л. В., Ванько Л.В., Адамян Л.В. Эффекторные и регуляторные субпопуляции клеток врожденного иммунитета в периферической крови и перитонеальной жидкости женщин с эндометриозом. Акушерство и гинекология. 2021; 6: 96-104.
  25. Capobianco А., Rovere-Querini Р. Endometriosis, a disease of the macrophage. Front. Immunol. 2013; 4: 9. https://dx.doi.org/10.3389/fimmu.2013.00009.

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