FEATURES OF SYSTEM IMMUNITY IN WOMEN WITH ENDOMETRIOSIS AND GENITAL INFECTION

External genital endometriosis is an inflammatory, estrogen-dependent disease that develops predominantly in women of reproductive age and is characterized by the presence of pain syndrome and infertility. Today, endometriosis is one of the most common gynecological diseases in women of reproductive age, however, the etiology and pathogenesis of it are not completely clear. Violations of systemic immunity are most important in the pathogenesis of endometriosis. The literature data on the features of the immune response in endometriosis in combination with genital infection are few and contradictory. Purpose – to study the features of systemic immunity in women with external genital endometriosis and pathogens of genital infection.

A total of 159 women with external genital endometriosis were examined. The main lymphocyte subpopulations, the functional activity of neutrophils and peripheral blood monocytes, and the content of cytokines in the blood serum were studied. A study of systemic immunity was performed in women with 1-2 and 3-4 stages of endometriosis, as well as depending on the presence of pathogens of genital infection. The presence of Chlamydia trachomatis, Ureaplasma spp., Mycoplasma genitalium, HSV1, 2/CMV, HPV in the endometrium, peritoneal fluid, and endometrioid heterotopies was determined. Statistical processing was performed using the IBM SPSS Statistics Version 22.2 statistical analysis software package.

According to the results of the study, it was found that women with endometriosis of stages 1-2 show signs of systemic inflammation with a predominance of the Th2 type of immune response and inhibition of cellular immunity. A particular feature of HPV was an increase in T-NK lymphocytes, a decrease in IL-2 and neutrophil functional activity. The presence of Ureaplasma spp./Mycoplasma genitalium was characterized by a decrease in cellular immunity and an increase in T-NK cells. Only with HPV and Ureaplasma spp./Mycoplasma genitalium decreased synthesis of IL-2, IL-6. With 3-4 stages, the most significant changes in immunity were found in groups of women with genital infection. When HPV – a high level of IgA, increased IgM, IL-8. With Ureaplasma spp./Mycoplasma genitalium – inhibition of cellular immunity, high levels of IgA, reduction of neutrophil phagocytic activity.

Thus, in women with endometriosis in the presence of pathogens of genital infection revealed features that may contribute to the development and progression of the disease.

1. Adamyan L.V., Aznaurova Ya.B. Molecular aspects of the pathogenesis of endometriosis. Problemy reproduktsii = Reproduction Problems, 2015, Vol. 21, no. 2, pp. 66-77. (In Russ.)

2. Adamyan L.V., Kulakov V.I., Andreeva E.N. Endometriosis. Moscow: Medicine, 2006. 411 p.

3. Adamyan L.V., Farkhat K.N., Makiyan Z.N., Savilova A.M. Molecular and biological characteristics of eutopic and ectopic endometrium (literature review). Problemy reproduktsii = Reproduction Problems, 2015, Vol. 21, no. 5, pp. 8-16. (In Russ.)

4. Enkova E.V., Strygina K.Kh. Characteristic indicators of immune homeostasis of patients with external genital endometriosis. Prikladnye informatsionnye aspekty meditsiny = Applied Information Aspects of Medicine, 2014, Vol. 17, no. 2, pp. 78-86. (In Russ.)

5. Ketlinsky S.A. The role of T-helper types 1 and 2 in the regulation of cellular and humoral immunity. Immunologiya = Immunology, 2002, Vol. 23, no. 2, pp. 77-79. (In Russ.)

6. Leskov V.P., Gavrilova E.F., Pishchulin A.A. Changes in the immune system with internal endometriosis. Problemy reproduktsii = Reproduction Problems, 1998, no. 4, pp. 26-30. (In Russ.)

7. Lud L.N. The role of sexually transmitted infections in the pathogenesis of genital endometriosis. Okhrana materinstva i detstva = Protection of Motherhood and Childhood, 2002, no. 3, pp. 37-42. (In Russ.)

8. Savchenko A.A., Tskhay V.B., Kruglova D.Yu., Borisov A.G. Immunological indicators during mono-infection with human papillomavirus and combined human papillomavirus and urogenital infections. Infektsiya i immunitet = Russian Journal of Infection and Immunity, 2014, Vol. 4, no. 3, pp. 241-248. (In Russ.) doi: 10.15789/2220-7619-2014-3-241-248.

9. Sotnikova N.Yu., Antsiferova Yu.S., Malyshkina A.I., Krasilnikova A.K. Disorders of systemic reactions of innate immunity in patients with infertility and endometriosis stage I-II and the possibility of their correction by the drug licopid. Immunologiya = Immunology, 2016, Vol. 37, no. 1, pp. 17-21. (In Russ.)

10. Tikhonchuk E.Yu., Nepsha O.S., Adamyan L.V., Kuznetsova M.V. Omix technology in the study of the pathogenesis of endometriosis (literature review). Problemy reproduktsii = Reproduction Problems, 2016, Vol. 22, no. 5, pp. 110- 122. (In Russ.)

11. Endometriosis: diagnosis, treatment and rehabilitation. Federal clinical guidelines for the management of patients. Moscow, 2016. 66 р.

12. Yarmolinskaya M.I., Molotkov A.S., Bezhenar V.F., Kvetnoy I.M. The effectiveness of aromatase inhibitors in the combined treatment of external genital endometriosis. Arkhiv akusherstva i ginekologii im. V.F. Snegireva = V. Snegirev Archive of Obstetrics and Gynecology, 2014, Vol. 1, no. 1, pp. 36-40. (In Russ.)

13. Ahn S.H., Monsanto S.P., Miller C., Singh S.S., Thomas R., Tayade C. Pathophysiology and immune dysfunction in  endometriosis. Biomed Res. Int., 2015, Vol. 2015, 795976. doi: 10.1155/2015/795976.

14. Campos G.B., Marques L.M., Rezende I.S., Barbosa M.S., Abrão M.S., Timenetsky J. Mycoplasma genitalium can modulate the local immune response in patients with endometriosis. Fertil. Steril., 2018, Vol. 109, no. 3, pp. 549- 560.e4.

15. Heidarpour M., Derakhshan M., Derakhshan-Horeh M., Kheirollahi M., Dashti S. Prevalence of high-risk human papillomavirus infection in women with ovarian endometriosis. J. Obstet. Gynaecol., 2017, Vol. 43, no. 1, pp. 135-139.

16. Kobayashi H., Higashiura Y., Shigetomi H., Kajihara H. Pathogenesis of endometriosis: the role of initial infection and subsequent sterile inflammation (Review). Mol. Med. Rep., 2014, Vol. 9, no. 1, pp. 9-15.

17. Kajihara H., Yamada Y., Kanayama S., Furukawa N., Noguchi T., Haruta S., Yoshida S., Sado T., Oi H., Kobayashi H. New insights into the pathophysiology of endometriosis: from chronic inflammation to danger signal. Gynecol. Endocrinol., 2011, Vol. 27, no. 2, pp. 73-79.

18. Khan K.N., Kitajima M., Hiraki K., Fujishita A., Sekine I., Ishimaru T., Masuzaki H. Toll-like receptors in innate immunity: role of bacterial endotoxin and toll-like receptor 4 in endometrium and endometriosis. Gynecol. Obstet. Invest., 2009, Vol. 68, no. 1, pp. 40-52.

19. Khoufache K., Michaud N., Harir N., Kibangou Bondza P., Akoum A. Anomalis in the inflammatory response in endometriosis and possible consequences: a review. Minerva Endocrinol., 2012, Vol. 37, no. 1, pp. 75-92.

20. Macer M.L., Taylor H.S. Endometriosis and infertility: A review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet. Gynecol. Clin. North Am., 2012, Vol. 39, pp. 535-549.

21. Mălutan A.M., Drugan T., Ciortea R., Bucuri C., Rada M.P., Mihu D. Endometriosis-associated changes in serum levels of interferons and chemokines. Turk. J. Med. Sci., 2017, Vol. 47, no. 1, pp. 115-122.

22. Matarese G., de Placido G., Nicas Y., Alviggi C. Patogenesis of endometriosis: natural immunity disfunction or autoimmune disease. Trends Mol. Med., 2003, Vol. 9, no. 5, pp. 223-228.

23. Oppelt P., Renner S.P., Strick R., Valletta D., Mehlhorn G., Fasching P.A., Beckmann M.W., Strissel P.L. Correlation of high-risk human papilloma viruses but not of herpes viruses or Chlamydia trachomatis with endometriosis lesions. Fertil. Steril., 2010, Vol. 93, no. 6, pp. 1778-1786.

24. Othman E.R., Hornung D., Hussein M., Abdelaal I.I., Sayed A.A., Fetih A.N., Al-Hendy A. Soluble tumor necrosis factor-alpha receptors in the serum of endometriosis patients. Eur. J. Obstet. Gynecol. Reprod. Biol., 2016, Vol. 200, pp. 1-5.

25. Santulli P., Borghese B., Chouzenoux S., Vaiman D., Borderie D., Streuli I., Goffinet F., de Ziegler D., Weill B., Batteux F., Chapron C. Serum and peritoneal interleukin-33 levels are elevated in deeply infiltrating endometriosis. Hum. Reprod., 2012, Vol. 27, no. 7, pp. 2001-2009.

26. Signorile P. G., Baldi A. Endometriosis: new concepts in the pathogenesis. Int. J. Biochem. Cell. Biol., 2010, Vol. 42, no. 6, pp. 778-780.

27. Sikora J., Mielczarek-Palacz A., Kondera-Anasz Z. Role of natural killer cell activity in the pathogenesis of endometriosis. Curr. Med. Chem., 2011, Vol. 18, no. 2, pp. 200-208.

28. Sourial S., Tempest N., Hapangama D.K. Theories on the pathogenesis of endometriosis. Int. J. Reprod. Med., 2014, Vol. 2014, 179515. doi: 10.1155/2014/179515.

29. Vestergaard A.L., Knudsen U.B., Munk T., Rosbach H., Bialasiewicz S., Sloots T.P., Martensen P.M., Antonsson A. Low prevalence of DNA viruses in the human endometrium and endometriosis. Arch. Virol., 2010, Vol. 155, no. 5, pp. 695-703.