Immunogenetic mechanisms of recurrent pathological vaginal discharge in women of reproductive age
Uruymagova A.T., Mezhevitinova E.A., Donnikov A.E.
Objective: To identify immunogenetic factors that predispose women of reproductive age to recurrent pathological vaginal discharge.
Materials and methods: This study enrolled 173 women of reproductive age: 59 with episodic pathological vaginal discharge, 74 with recurrent pathological discharge, and 40 healthy women (control group). Genotyping of single nucleotide polymorphisms (SNPs) in immune-regulatory genes (CD14, CTLA4, IFN-γ, IGF-2, IL-10, IL-12β, IL-18, IL-1α, IL-1β, IL-1R, IL-2, IL-4, IL-4R, IL-6, IL-6R, IL-8, TGFβ1, TNF, and MBL2) and genes associated with the neuroendocrine stress response (CRH, CRHR1, and CRHR22) was performed using PCR-based SNP typing. The expression of cytokine (IL-1β, IL-10, IL-18, and TNF-α) and innate immunity receptor (TLR4) mRNAs in vaginal samples was measured by real-time RT-PCR. Statistical analysis included comparisons of allele/genotype frequencies, risk ratio (RR) calculations with 95% confidence intervals, χ² test, Mann–Whitney test, and multivariate logistic regression (significance at p<0.05).
Results: Recurrent pathological vaginal discharge was associated with alterations in local immune response. In the group with recurrent inflammatory discharge, there was significantly increased expression of the anti-inflammatory cytokine IL-10 and decreased IL-18 expression compared to episodic cases, indicating an imbalance in immune regulation. Patients with non-inflammatory recurrences exhibit a different immune profile, characterized by elevated levels of the pro-inflammatory cytokines TNF-α and IL-10. Statistically significant associations were identified between genetic variants and disease recurrence. The GG genotype of the IL-10 -1082 G>A polymorphism increased the risk of recurrent pathological discharge of both inflammatory and non-inflammatory origins, whereas the GG genotypes of the TNF-α -238 G>A polymorphism and CRHR1 (rs17689966) polymorphism significantly increased the likelihood of recurrence in cases of non-inflammatory discharge.
Conclusion: Recurrence of pathological vaginal discharge is driven by a combination of local immune imbalance and genetic predisposition. Polymorphisms in immune-related genes (IL-10, TNF, and CRHR1) may serve as molecular genetic markers of recurrence risk, paving the way for personalized prevention and treatment strategies.
Authors' contributions: Uruymagova A.T., Mezhevitinova E.A., Donnikov A.E. – conception and design of the study, obtaining data for analysis, review of relevant literature, analysis of the obtained data, drafting of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: There was no funding for this study.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Uruymagova A.T., Mezhevitinova E.A., Donnikov A.E. Immunogenetic mechanisms of
recurrent pathological vaginal discharge in women of reproductive age.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (7): 103-111 (in Russian)
https://dx.doi.org/10.18565/aig.2025.138
Keywords
immunogenetics
recurrent vaginal discharge
bacterial vaginosis
aerobic vaginitis
gene polymorphisms
cytokines
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Received 27.05.2025
Accepted 18.06.2025
About the Authors
Ada T. Uruymagova, PhD student at the Department of Obstetrics, Gynecology, Perinatology and Reproductology, V.I. Kulakov NMRC for OGP, Ministry of Health of Russia, 4 Ac. Oparina str., Moscow, 117997, Russia, +7(925)704-33-97, ada.uruimagova@yandex.ru, https://orcid.org/0000-0001-5650-3377Elena A. Mezhevitinova, Dr. Med. Sci., Leading Researcher at the Scientific and Outpatient Department, V.I. Kulakov NMRC for OGP, Ministry of Health of Russia,
4 Ac. Oparina str., Moscow, 117997, Russia, mejevitinova@mail.ru, https://orcid.org/0000-0003-2977-9065
Andrey E. Donnikov, PhD, Head of the Laboratory of Molecular Genetic Methods, V.I. Kulakov NMRC for OGP, Ministry of Health of Russia,
4 Ac. Oparina str., Moscow, 117997, Russia, https://orcid.org/0000-0003-3504-2406
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