Natural killer cell immunoglobulin-like receptors and their ligands in spouses and pregnancy outcomes of recurrent miscarriage treated with immunocytic therapy
Krechetova L.V., Khoroshkeeva O.V., Tetruashvili N.K., Krechetov S.P., Jankevic T.E., Inviyaeva E.V., Trofimov D.Yu., Sukhikh G.T.
Relevance: Impaired fetoplacental blood flow is a primary cause of early pregnancy loss. The formation of the vascular bed during endometrial decidualization and control of trophoblast invasion involves natural killer (NK) cells, which express killer cell immunoglobulin-like receptors (KIR). The action of NK cells on target cells is determined by the interaction between the KIR and HLA class I molecules (HLA I). The characteristics of maternal and paternal KIR and HLA I molecules, which are KIR (KIR-L) ligands, as well as the NK cell-mediated allocompatibility reactions they induce have the potential to influence the efficacy of immunocytic therapy (ICT) during pregnancy.
Objective: To perform typing of classical HLA I and KIR genes in patients and their spouses among couples with idiopathic recurrent miscarriage (RM) to identify the characteristics of KIR genotypes and KIR-L representation in spouses with different pregnancy outcomes.
Materials and methods: This study included 39 married couples with RM. ICT was performed twice for each couple, both outside and during pregnancy. KIR and HLA I gene typing was conducted using maternal and paternal peripheral blood samples. Typing was performed using high-throughput NGS sequencing.
Results: Typing of KIR genes and classical HLA I genes in patients from married couples with idiopathic RM and treatment using ICT did not reveal any specific characteristics of KIR and KIR-L in spouses. Additionally, no association was found between the characteristics of KIR and KIR-L in spouses and pregnancy outcomes that occurred after ICT. These results do not provide sufficient evidence to suggest that KIR genotypes and classical HLA I in spouses are prerequisites for mother-fetus alloincompatibility in RM. Furthermore, the data did not reveal any combinations of KIR and KIR-L in spouses that affect the effectiveness of treatment involving ICT.
Conclusion: The lack of connection between the results of RM treatment involving ICT and the characteristics of the KIR genotypes and classical HLA I of spouses emphasizes the need for further investigation into the immunological processes involved in allogeneic mother-fetus interaction during pregnancy and maternal and paternal ICT. One promising area for further research is the study of KIR gene expression in NK cells of women with normal and pathological pregnancies.
Authors' contributions: Tetruashvili N.K., Trofimov D.Yu., Sukhikh G.T. – conception and design of the study; Khoroshkeeva O.V. – selection of clinical samples; Tetruashvili N.K., Khoroshkeeva O.V. – clinical examination of patients, obtaining biospecimens; Jankevic T.E. – KIR and HLA typing of biological samples; Krechetov S.P., Khoroshkeeva O.V., Krechetova L.V. – analysis of clinical and laboratory data, drafting of the manuscript; Inviyaeva E.V. – editing 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 (Ref. No: 35 of 09.04.2009).
Patient Consent for Publication: The couple signed a voluntary 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: Krechetova L.V., Khoroshkeeva O.V., Tetruashvili N.K., Krechetov S.P., Jankevic T.E., Inviyaeva E.V., Trofimov D.Yu., Sukhikh G.T. Natural killer cell immunoglobulin-like receptors and their ligands in spouses and pregnancy outcomes of recurrent miscarriage treated with immunocytic therapy.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (11): 98-108 (in Russian)
https://dx.doi.org/10.18565/aig.2024.261
Keywords
recurrent miscarriage
NK cells
immunoglobulin-like receptors of killer cells
genotyping
immunocytic therapy
mother
father
pregnancy outcomes
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Received 21.10.2024
Accepted 12.11.2024
About the Authors
Lyubov V. Krechetova, Dr. Med. Sci., Head of the Laboratory of Clinical Immunology, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Oparin str., 4, l_krechetova@oparina4.ru, https://orcid.org/0000-0001-5023-3476Olga V. Khoroshkeeva, Obstetrician-Gynecologist at the Department of Pregnancy Disorders (Miscarriage Treatment and Prevention Unit), V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Oparin str., 4, o_khoroshkeeva@oparina4.ru, https://orcid.org/0000-0002-5153-5422
Nana K. Tetruashvili, Dr. Med. Sci., Head of the Department of Pregnancy Disorders (Miscarriage Treatment and Prevention Unit), V.I. Kulakov NMRC for OG&P,
Ministry of Health of Russia, 117997, Russia, Moscow, Oparin str., 4, n_tetruashvili@oparina4.ru, https://orcid.org/0000-0002-9201-2281
Sergey P. Krechetov, PhD, Leading Researcher at the Laboratory of Clinical Immunology, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Oparin str., 4, s_krechetov@oparina4.ru, https://orcid.org/0000-0003-2861-6010
Tatjana E. Jankevic, PhD, Junior Researcher at the Human Histocompatibility Genetics Laboratory, NRC Institute of Immunology, FMBA of Russia, 115522, Russia, Moscow, Kashirskoye Shosse, 24, tat-shapovalov@yandex.ru, https://orcid.org/0000-0002-0105-3812
Evgenya V. Inviyaeva, PhD, Leading Researcher at the Laboratory of Clinical Immunology, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia,
117997, Russia, Moscow, Oparin str., 4, e_inviyaeva@oparina4.ru, https://orcid.org/0000-0001-9878-3637
Dmitry Yu. Trofimov, Corresponding Member of the RAS, Dr. Bio. Sci., Director of the Institute of the Reproductive Genetics, V.I. Kulakov NMRC for OG&P,
Ministry of Health of Russia, 117997, Russia, Moscow, Oparin str., 4, d_trofimov@oparina4.ru, https://orcid.org/0000-0002-1569-8486
Gennady T. Sukhikh, Academician of the RAS, Dr. Med. Sci., Professor, Director, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow,
Oparin str., 4, g_sukhikh@oparina4.ru, https://orcid.org/0000-0002-7712-1260
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