Natural killer cell immunoglobulin-like receptors and their ligands in spouses and pregnancy outcomes of recurrent miscarriage treated with immunocytic therapy

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Abstract

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.

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About the authors

Lyubov V. Krechetova

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Author for correspondence.
Email: l_krechetova@oparina4.ru
ORCID iD: 0000-0001-5023-3476

Dr. Med. Sci., Head of the Laboratory of Clinical Immunology

 

Russian Federation, 117997, Moscow, Oparin str., 4

Olga V. Khoroshkeeva

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: o_khoroshkeeva@oparina4.ru
ORCID iD: 0000-0002-5153-5422

Obstetrician-Gynecologist at the Department of Pregnancy Disorders (Miscarriage Treatment and Prevention Unit)

Russian Federation, 117997, Moscow, Oparin str., 4

Nana K. Tetruashvili

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: n_tetruashvili@oparina4.ru
ORCID iD: 0000-0002-9201-2281

Dr. Med. Sci., Head of the Department of Pregnancy Disorders (Miscarriage Treatment and Prevention Unit)

Russian Federation, 117997, Moscow, Oparin str., 4

Sergey P. Krechetov

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: s_krechetov@oparina4.ru
ORCID iD: 0000-0003-2861-6010

PhD, Leading Researcher at the Laboratory of Clinical Immunology

Russian Federation, 117997, Moscow, Oparin str., 4

Tatjana E. Jankevic

National Research Center – Institute of Immunology Federal Medical-Biological Agency of Russia

Email: tat-shapovalov@yandex.ru
ORCID iD: 0000-0002-0105-3812

PhD, Junior Researcher at the Human Histocompatibility Genetics Laboratory

Russian Federation, 115522, Moscow, Kashirskoye Shosse, 24

Evgenya V. Inviyaeva

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: e_inviyaeva@oparina4.ru
ORCID iD: 0000-0001-9878-3637

PhD, Leading Researcher at the Laboratory of Clinical Immunology

Russian Federation, 117997, Moscow, Oparin str., 4

Dmitry Yu. Trofimov

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: d_trofimov@oparina4.ru
ORCID iD: 0000-0002-1569-8486

Corresponding Member of the RAS, Dr. Bio. Sci., Director of the Institute of the Reproductive Genetics

Russian Federation, 117997, Moscow, Oparin str., 4

Gennady T. Sukhikh

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: g_sukhikh@oparina4.ru

Academician of the RAS, Dr. Med. Sci., Professor, Director

Russian Federation, 117997, Moscow, Oparin str., 4

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Supplementary files

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2. Fig. 1. The proportion of K1P gene carriers in patients with PV treated with ICT and their spouses

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3. Fig. 2. The proportion of carriers of the K1B genes (A, B) and K1P genotypes (B, D) among patients with PV (A, B) and their spouses (B, D), taking into account pregnancy outcomes after treatment with ICT

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4. Fig. 3. The proportion of K1A-b carriers among patients with PV (A) and their spouses (B), taking into account pregnancy outcomes after treatment using ICT

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5. Fig. 4. Indicators of MK-cell tuning in mother-father pairs during ICT in relation to individual IK1N-1 and the presence of at least one combination of IK1R-|K1R-k (M(IK1R-k)> 1) in a married couple, taking into account pregnancy outcomes after treatment

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