Proliferative endometrial diseases: cytokine and macroglobulin spectrum
Sabantsev M.A., Shramko S.V., Zorina V.N.
Objective: To explore serum concentrations of cytokines and macroglobulins in patients with different proliferative endometrial diseases.
Materials and methods: A case-control study included 197 women who were divided into 5 groups based on the results of histological examination of the endometrium: endometrial polyps (EP) – 58 cases, endometrial hyperplasia without atypia (EH) – 52, endometrial atypical hyperplasia (AH) – 24, endometrial cancer (EC) – 42, and the control group (С) – 21 women. Enzyme-linked immunosorbent assay and rocket immunoelectrophoresis were used to determine the concentrations of α₂-macroglobulin (α₂M), pregnancy-associated α₂-glycoprotein (PAG) and their immune complexes with IgG (PAG-IgG, α₂M-IgG), lactoferrin (LF), interleukins (IL-6, IL-8), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFNγ).
Results: The progressive increase in concentrations of VEGF(11-fold higher in EC compared with the control group), TNF-α (15-fold higher compared with the control group), as well as elevated levels of immune complexes α₂M-IgG, and PAG-IgG, and significantly reduced LF levels were found in the spectrum of diseases EP"EH"AH"EC. EH was associated with significantly high IL-8 levels (65.69±11.17 pg/mL), while AH showed low levels of IFNγ.
Conclusion: Proliferative endometrial diseases exhibit specific serum cytokine and macroglobulin profiles reflecting increased angiogenic activity, enhanced immune complex formation, and depletion of anti-inflammatory capacity with disease progression. The obtained data show the important role of immune and inflammatory mechanisms and open prospects for developing new diagnostic and therapeutic algorithms.
Authors' contributions: Sabantsev M.A., Shramko S.V. – the study concept and designs, material collection and processing; Sabantsev M.A. – statistical data processing, manuscript writing; Shramko S.V., Zorina V.N. – manuscript editing.
Conflicts of interest: The authors confirm that they have no conflicts of interest. The authors declare their authorship in compliance with the ICMJE criteria.
Funding: The study was carried out and the article was published without any sponsorship.
Ethical Approval: The study was approved by the local Ethics Committee of Novokuznetsk State Institute for Further Training of Physicians – Branch Campus of the Russian Medical Academy of Continuous Professional Education, Ministry of Health of Russia (protocol No. 4 of June, 2024).
Patient Consent for Publication: The patients have signed informed consent for participation in the study and publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator..
For citation: Sabantsev M.A., Shramko S.V., Zorina V.N. Proliferative endometrial diseases:
cytokine and macroglobulin spectrum.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (4): 121-127 (in Russian)
https://dx.doi.org/10.18565/aig.2025.347
Keywords
endometrial polyps
endometrial hyperplasia
endometrial cancer
cytokine
macroglobulin
immune complexes
endothelial growth factor
tumor necrosis factor
interleukin
interferon-gamma
References
- Seshagiri P.B., Vani V., Madhulika P. Cytokines and blastocyst hatching. Am. J. Reprod. Immunol. 2016; 75(3): 208-17. https://dx.doi.org/10.1111/aji.12464
- Pachomov C.P., Altuchova O.B., Demakova N.A, Krivoshei I.V., Kolesnikov Y.V., Sobyanin F.I. Study of cytokines polymorphous loci connections with rise of endometrium proliferative diseases. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2014; 5(6): 1473-6.
- Министерство здравоохранения Российской Федерации. Клинические рекомендации. Полипы эндометрия. 2023. [Ministry of Health of the Russian Federation. Clinical guidelines. Endometrial polyps. 2023 (in Russian)].
- Министерство здравоохранения Российской Федерации. Клинические рекомендации. Гиперплазия эндометрия. 2025. [Ministry of Health of the Russian Federation. Clinical guidelines. Endometrial hyperplasia. 2025 (in Russian)].
- Зорина В.Н., Зорина Р.М., Левченко В.Г., Воронина Е.А., Зорин Н.А. Концентрация комплексов макроглобулин-IgG как возможный критерий для прогнозирования гестоза и оценки степени его тяжести. Клиническая и лабораторная диагностика. 2001; 8: 48-9. [Zorina V.N., Zorina R.M., Levchenko V.G., Voronina E.A., Zorin N.A. Macroglobulin-IgG complex con- centration as a criterion for prognosis of gestosis and assessment of its severity. Clinical and Laboratory Diagnostics. 2001; 8: 48-9 (in Russian)].
- Ray I., Michael A., Meira L.B., Ellis P.E. The role of cytokines in epithelial-mesenchymal transition in gynaecological cancers: a systematic review. Cells. 2023; 12(3): 416. https://dx.doi.org/10.3390/cells12030416
- Сабанцев М.А., Шрамко С.В., Левченко В.Г., Волков О.А., Третьякова Т.В. Гиперплазии эндометрия: без атипии и с атипией. Гинекология. 2021; 23(1): 18-24. [Sabantsev M.A., Shramko S.V., Levchenko V.G., Volkov O.A., Tretyakova T.V. Endometrial hyperplasia: without atypia and with atypia. Ginekology. 2021; 23(1): 18-24 (in Russian)]. https://dx.doi.org/10.26442/20795696.2021.1.200666
- Дятлова Л.И., Глухова Т.Н., Понукалина Е.В., Сергеева О.Н., Бизенкова М.Н. О значении дисбаланса цитокинов в патогенезе рака эндометрия. Современные проблемы науки и образования. 2024; 3: 8. [Dyatlova L.I., Glukhova T.N., Ponukalina E.V., Mikhailova Yu.V., Bizenkova M.N. About the significance of cytokine imbalance in the pathogenesis of endometrial cancer. Modern Problems of Science and Education. 2024; 3: 8 (in Russian)]. https://dx.doi.org/10.17513/spno.33412
- Gocher A.M., Workman C.J., Vignali D.A.A. Interferon-γ: teammate or opponent in the tumour microenvironment? Nat. Rev. Immunol. 2022; 22(3): 158-72. https://dx.doi.org/10.1038/s41577-021-00566-3
- Nimmerjahn F., Ravetch J.V. Fcgamma receptors as regulators of immune responses. Nat. Rev. Immunol. 2008; 8(1): 34-47. https://dx.doi.org/10.1038/nri2206
- Кравченко Е.Н., Лаутеншлегер Е.В. Гиперплазия эндометрия и полипы эндометрия: клинико-анамнестическая характеристика женщин. Фундаментальная и клиническая медицина. 2023; 8(4): 16-23. [Kravchenko E.N., Lautenschleger E.V. Endometrial hyperplasia and endometrial polyps: clinical and anamnestic characteristics of women. Fundamental and Clinical Medicine. 2023; 8(4): 16-23 (in Russian)]. https://dx.doi.org/10.23946/2500-0764-2023-8-4-16-23
- Ткаченко Л.В., Свиридова Н.И., Жаркин Н.А., Бурова Н.А., Белан Э.Б. Оценка цитокинового статуса у пациенток с хроническим эндометритом в сочетании с гиперпластическими процессами эндометрия в репродуктивном периоде. Инфекция и иммунитет. 2020; 10(4): 762-8. [Tkachenko L.V., Sviridova N.I., Zharkin N.A., Burova N.A., Belan E.B. Assessing cytokine status of patients with chronic endometritis combined with endometrial hyperplastic processes in reproductive period. Russian Journal of Infection and Immunity. 2020; 10(4): 762-8 (in Russian)]. https://dx.doi.org/10.15789/2220-7619-AOC-1357
- Серебренникова К.Г., Арутюнян Н.А., Кацалап С.Н., Алехин А.И. Фотодинамическая терапия у пациенток с бесплодием при хроническом эндометрите. Российский вестник акушера-гинеколога. 2020; 20(3): 56-61. [Serebrennikova K.G., Arutyunyan N.A., Katsalap S.N., Alekhin A.I. Photodynamic therapy in patients with infertility in chronic endometritis. Russian Bulletin of Obstetrician-Gynecologist. 2020; 20(3): 56-61 (in Russian)]. https://dx.doi.org/10.17116/rosakush20202003156
- Оразов М.Р., Радзинский В.Е., Хамошина М.Б., Михалева Л.М., Муллина И.А., Артеменко Ю.С. Предикторы рецидивирующего течения эндометриальной гиперплазии без атипии у женщин репродуктивного возраста. Клинический разбор в общей медицине. 2023; 4(9): 16-20. [Orazov M.R., Radzinsky V.E., Khamoshina M.B., Mikhaleva L.M., Mullina I.A., Artemenko Yu.S. Predictors of recurrent course of endometrial hyperplasia without atypia in women of reproductive age. Clinical review for general practice. 2023; 4(9): 16-20 (in Russian)]. https://dx.doi.org/10.47407/kr2023.4.9.00304
- Белявская С.А., Дикарева Л.В. Хронический эндометрит как фактор риска пролиферативных заболеваний матки: современные подходы к диагностике. Обзор литературы. Главный врач Юга России. 2024; 4(96): 2-7. [Belyavskaya S.A., Dikareva L.V. Chronic endometritis as a risk factor for proliferative diseases of the uterus: modern approaches to diagnosis. Literature review. Glavnyj vraсh Yuga Rossii. 2024; 4(96): 2-7 (in Russian)].
- Moreno I., Cicinelli E., Garcia-Grau I., Gonzalez-Monfort M., Bau D., Vilella F. et al. The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology. Am. J. Obstet. Gynecol. 2018; 218(6): 602.e1-e16. https://dx.doi.org/10.1016/j.ajog.2018.02.012
- Carvalho F.M., Aguiar F.N., Tomioka R., de Oliveira R.M., Frantz N., Ueno J. Functional endometrial polyps in infertile asymptomatic patients: a possible evolution of vascular changes secondary to endometritis. Eur. J. Obstet. Gynecol. Reprod. Biol. 2013; 170(1): 152-6. https://dx.doi.org/10.1016/j.ejogrb.2013.05.012
- Оразов М.Р., Михалева Л.М., Пойманова О.Ф. Гистероскопическая диагностика полипов эндометрия, ассоциированных с хроническим эндометритом. Акушерство и гинекология: новости, мнения, обучение. 2024; 12(Спецвып.): 141-7. [Orazov M.R., Mikhaleva L.M., Poimanova O.F. Hysteroscopic diagnosis of endometrial polyps associated with chronic endometritis. Obstetrics and Gynecology: News, Opinions, Training. 2024; 12(S): 141-7 (in Russian)]. https://dx.doi.org/10.33029/2303-9698-2024-12-suppl-141-147
Received 01.12.2025
Accepted 09.04.2026
About the Authors
Maksim A. Sabantsev, PhD student at the Department of Obstetrics and Gynecology, Novokuznetsk State Institute for Further Training of Physicians – Branch Campus of the Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russian Federation, 654005, Russia, Novokuznetsk, Stroiteley Ave., 5,+7(913)333-23-22, Dr.Sabantsev@ya.ru, https://orcid.org/0000-0001-7104-1852
Svetlana V. Shramko, Dr. Med. Sci., Associate Professor, Professor at the Department of Obstetrics and Gynecology, Novokuznetsk State Institute for Further Training of Physicians – Branch Campus of the Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russian Federation, 654005, Russia, Novokuznetsk, Stroiteley Ave., 5, +7(961)714-00-13, shramko_08@mail.ru, https://orcid.org/0000-0003-1299-165X
Veronika N. Zorina, Dr. Bio. Sci., Leading Researcher at the Laboratory of Applied Toxicology and Pharmacology of Toxicology Division, Golikov Research Center of Toxicology, 192019, Russia, St. Petersburg, Bekhtereva str., 1 lit A, +7(812)372-51-23, nilimmun@yandex.ru, https://orcid.org/0000-0001-9183-7663
Corresponding author: Maksim A. Sabantsev, Dr.Sabantsev@ya.ru
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