2026 / 03

Next Paper
DOI: 10.24075/brsmu.2026.036
Copyright: © 2026 by the authors. Licensee: Pirogov University.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (CC BY).

ORIGINAL RESEARCH

Immunomodulatory effects of the placental conditioned medium and HLA-DR-dependent mechanisms in carriers of the HLA-DRB1*01:01 alleles with preeclampsia

Sorokina LE1,2 , Kokoeva DN2 , Krasnyi AM2 , Fomochkina II1
About authors

1 V.I. Vernadsky Crimean Federal University, Simferopol, Russia

2 Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia

Correspondence should be addressed: Leya E. Sorokina
Akademika Oparina, 4, Moscow, 117198, Russia; ur.liam@anikoros.ayel

About paper

Author contribution: Sorokina LE — data acquisition, analysis, and interpretation, manuscript writing; Krasnyi AM — data acquisition, analysis, and interpretation, statistical data processing; Fomochkina II — study concept and design, manuscript writing.

Compliance with ethical standards: the study was approved by the Ethics Committee of the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology (protocol No. 11 dated November 11, 2021).

Received: 2026-05-10 Accepted: 2026-06-20 Published online: 2026-06-30
|
  1. Karrar SA, Martingano DJ, Hong PL. Preeclampsia. [Updated 2024 Feb 25]. In: StatPearls [Internet]. 2024 Feb (cited 2025 Apr 12). Available from: https://www.ncbi.nlm.nih.gov/books/NBK570611/
  2. Qin Z, Long Y. Immunological dysregulation in preeclampsia: Pathogenesis and clinical implications. Int Immunopharmacol. 2025; 163: 115314.
  3. Lu HQ, Hu R. The role of immunity in the pathogenesis and development of pre-eclampsia. Scand J Immunol. 2019; 90 (5): e12756.
  4. Than NG, Hahn S, Rossi SW, Szekeres-Bartho J. Editorial: Fetal- Maternal Immune Interactions in Pregnancy. Front Immunol. 2019; 10: 2729.
  5. Peng X, Chinwe Oluchi-Amaka I, Kwak-Kim J, Yang X. A comprehensive review of the roles of T-cell immunity in preeclampsia. Front Immunol. 2025; 16: 1476123.
  6. Romao-Veiga M, Ribeiro VR, Matias ML, Nunes PR, Romagnoli GG, Peracoli JC, et al. DAMPs are able to skew CD4+ T cell subsets and increase the inflammatory profile in pregnant women with preeclampsia. J Reprod Immunol. 2022; 149: 103470.
  7. Musakhodzhaeva DA, Rustamova NB, Sadykova HZ. Narushenie citokinovogo balansa u beremennyh zhenshchin s preeklampsiej. Rossijskij immunologicheskij zhurnal. 2024; 27 (4): 859–64. Russian.
  8. Eghbal-Fard S, Yousefi M, Heydarlou H, Ahmadi M, Taghavi S, Movasaghpour A, et al. The imbalance of Th17/Treg axis involved in the pathogenesis of preeclampsia. J Cell Physiol. 2019; 234 (4): 5106–16.
  9. Vargas-Rojas MI, Solleiro-Villavicencio H, Soto-Vega E. Th1, Th2, Th17 and Treg levels in umbilical cord blood in preeclampsia. J Matern Fetal Neonatal Med. 2016; 29 (10): 1642–5.
  10. Kwiatek M, Kwaśniewski W, Gęca T, Grywalska E, Rahnama- Hezavah M, Mertowski S, et al. Dysregulation of Treg/Th17 Balance and Intracellular Expression of IL21 and IL22 in the Pathogenesis of Gestational Hypertension. Journal of Clinical Medicine. 2025; 14 (20): 7288.
  11. Deer E, Herrock O, Campbell N, Cornelius D, Fitzgerald S, Amaral LM, et al. The role of immune cells and mediators in preeclampsia. Nat Rev Nephrol. 2023; 19: 257–70.
  12. Papapanagiotou A, Daskalaki MA, Gargalionis AN, Margoni A, Domali A, Daskalakis G, et al. The Role of Angiogenetic Factors in Preeclampsia. Int J Mol Sci. 2025; 26 (21): 10431.
  13. Schumacher A, Brachwitz N, Sohr S, Engeland K, Langwisch S, Dolaptchieva M, et al. Human chorionic gonadotropin attracts regulatory T cells into the fetal-maternal interface during early human pregnancy. Journal of Immunology. 2009; 182 (9): 5488–97.
  14. Schumacher A, Costa SD, Zenclussen AC. Endocrine factors modulating immune responses in pregnancy. Frontiers in Immunology. 2014; 5: 196.
  15. Seppälä M, Taylor RN, Koistinen H, Koistinen R, Milgrom E. Glycodelin: a major lipocalin protein of the reproductive axis with diverse actions in cell recognition and differentiation. Endocrine Reviews. 2009; 30 (7): 784–813.
  16. Lee CL, Lam KK, Koistinen H, Seppala M, Kurpisz M, Fernandez N, et al. Glycodelin-A as a paracrine regulator in early pregnancy. Human Reproduction Update. 2016; 22 (5): 635–50.
  17. Munson PV, Adamik J, Butterfield LH. Immunomodulatory impact of α-fetoprotein. Trends Immunol. 2022; 43 (6): 438–48.
  18. Dendrou CA, Petersen J, Rossjohn J, Fugger L. HLA variation and disease. Nat Rev Immunol. 2018; 18 (5): 325–39.
  19. Aimagambetova G, Kapasheva A, Bahia W, Atageldiyeva K, Almawi WY. Maternal HLA class II alleles and haplotypes associated with altered risk of recurrent pregnancy loss: A case-control study. Am J Reprod Immunol. 2024; 91 (2): e13817.
  20. Boldyreva MN, Haitov RM, Barceva OB, Guzov II, Barkov IYu, i dr. Issledovanie roli HLA-DRB1-genov pri nevynashivanii beremennosti neyasnogo geneza. Immunologiya. 2004; 1: 4–8. Russian.
  21. Gordeeva LA, SHabaldin AV, Glushkov AN, Glushkova OA, Makarchenko OS, Simonova TA, i dr. Associaciya HLA-DRB1* s reproduktivnoj patologiej u zhenshchin. Medicinskaya immunologiya. 2007; 9 (6): 643–8. Russian.
  22. Takakuwa K, Honda K, Ishii K, Hataya I, Yasuda M, Tanaka K. Studies on the HLA-DRB1 genotypes in Japanese women with severe pre-eclampsia positive and negative for anticardiolipin antibody using a PCR-RFLP method. Human Reproduction. 1999; 14 (12): 2980–6.
  23. Krasnyi AM, Sorokina LE, Argentova-Stevens AM, Kokoeva DN, Alekseev AA, et al. Antibody-Dependent Cytotoxicity of Monocytes in Preeclampsia Is Associated with Soluble Forms of HLA. International Journal of Molecular Sciences. 2025; 26 (23): 11638.
  24. Aisagbonhi O, Morris GP. Human Leukocyte Antigens in Pregnancy and Preeclampsia. Front Genet. 2022; 13: 884275.
  25. Medeiros LT, Peracoli JC, Romao M, Bannwart-Castro CF, Golim MA, Borges VT, et al. M1 Monocyte subpopulation is associated with pro-inflammatory cytokineproduction in pregnant women with preeclampsia. Pregnancy Hypertens. 2012; 2 (3): 276–7.
  26. Veenstra van Nieuwenhoven AL, Heineman MJ, Faas MM. The immunology of successful pregnancy. Hum Reprod Update. 2003; 9: 347–57.
  27. Wang J, Tao YM, Cheng XY, Zhu TF, Chen ZF, Yao H, et al. Dendritic cells derived from preeclampsia patients influence Th1/Th17 cell differentiation in vitro. Int J Clin Exp Med. 2014; 7 (12): 5303–9.
  28. Joerger-Messerli MS, Hoesli IM, Rusterholz C, Lapaire O. Stimulation of monocytes by placental microparticles involves toll-like receptors and nuclear factor kappa-light-chain-enhancer of activated B cells. Front Immunol. 2014; 5: 173.
  29. La Rocca C, Carbone F, Longobardi S, Matarese G. The immunology of pregnancy: regulatory T cells control maternal immune tolerance toward the fetus. Immunol Lett. 2014; 162: 41–48.
  30. Bai K, Lee CL, Liu X, Li J, Cao D, Zhang L, et al. Human placental exosomes induce maternal systemic immune tolerance by reprogramming circulating monocytes. J Nanobiotechnology. 2022; 20 (1): 86.
  31. Carlé C, Degboe Y, Ruyssen-Witrand A, Arleevskaya MI, Clavel C, Renaudineau Y. Characteristics of the (Auto)Reactive T Cells in Rheumatoid Arthritis According to the Immune Epitope Database. International Journal of Molecular Sciences. 2023; 24 (5): 4296.
  32. Hoepel W, Newling M, Vogelpoel LTC, Sritharan L, Hansen IS, Kapsenberg ML, et al. FcγR-TLR Cross-Talk Enhances TNF Production by Human Monocyte-Derived DCs via IRF5-Dependent Gene Transcription and Glycolytic Reprogramming. Front Immunol. 2019; 10: 739.