Natural killer cell activity in women with recurrent miscarriage: Etiology and pregnancy outcome

Ebina, Yasuhiko; Nishino, Yukari; Deguchi, Masashi; Maesawa, Yoko; Nakashima, Yuki; Yamada, Hideto

doi:10.1016/j.jri.2017.04.005

Cited by 23 publications

(14 citation statements)

References 26 publications

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“…The significantly enhanced differentiation of naive T cells to CD8T effector cells, and preferential increasing in number of NK dim cells, together with the upregulated inflammation-related genes, demonstrate a systematic pro-inflammatory status in RSA patients. These results are consistent with previous reports (Ebina et al, 2017;Kuon et al, 2017). An interesting finding is the increased frequency of MAIT cells in RSA peripheral blood.…”

Section: Comparison Of the Differential Gene Expression In Dnk Subsetsupporting

confidence: 94%

Single-cell immune landscape of human recurrent spontaneous abortion

Wang

Jia

Fan

et al. 2020

Preprint

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SUMMARYSuccessful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus. Disorders in this process are tightly associated with adverse pregnancy outcomes including recurrent spontaneous abortion (RSA). However, an in-depth understanding of the disorders from the aspect of systematic and decidual immune environment in RSA remains largely lacking. In this study, we utilized single-cell RNA-sequencing to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and RSA pregnancies at the early stage of gestation. Integrative analysis identified 22 distinct cell clusters in total, and a dramatic difference in leukocyte subsets and molecular properties in RSA cases was revealed. Specifically, the cytotoxic properties of CD8T effector, NK, and MAIT cells in peripheral blood indicated apparently enhanced immune inflammatory status, and the subpopulation proportions and ligand-receptor interactions of the decidual leukocyte subsets demonstrated preferential immune activation in RSA patients. The molecular features, spatial distribution and the developmental trajectories of five decidual NK (dNK) subsets were illustrated. The proportion of a dNK subset responsible for fetal protection was reduced, while the ratio of another dNK subset with cytotoxic and immune-active signature was significantly increased. Notably, a unique pro-inflammatory CD56+CD16+ dNK subpopulation was substantially accumulated in RSA decidua. These findings reveal a comprehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy, which provides an in-depth insight into the immune pathogenesis for early pregnancy loss.

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Section: Comparison Of the Differential Gene Expression In Dnk Subsetsupporting

confidence: 94%

Single-cell immune landscape of human recurrent spontaneous abortion

Wang

Jia

Fan

et al. 2020

Preprint

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“…Ebina et al. revealed pre-pregnancy increased activities of pNK cells to be associated with pregnancy loss ( 131 ). Intravenous immunoglobulin (IVIG) has been shown to be efficacious treatment of uRPL, particularly in patients with increased numbers of NK cells.…”

Section: The Role Of Dnk Cells In Pathological Pregnancymentioning

confidence: 99%

Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications

Zhang

Wei

2021

Front. Immunol.

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Pregnancy is a unique type of immunological process. Healthy pregnancy is associated with a series of inflammatory events: implantation (inflammation), gestation (anti-inflammation), and parturition (inflammation). As the most abundant leukocytes during pregnancy, natural killer (NK) cells are recruited and activated by ovarian hormones and have pivotal roles throughout pregnancy. During the first trimester, NK cells represent up to 50–70% of decidua lymphocytes. Differently from peripheral-blood NK cells, decidual natural killer (dNK) cells are poorly cytolytic, and they release cytokines/chemokines that induce trophoblast invasion, tissue remodeling, embryonic development, and placentation. NK cells can also shift to a cytotoxic identity and carry out immune defense if infected in utero by pathogens. At late gestation, premature activation of NK cells can lead to a breakdown of tolerance of the maternal–fetal interface and, subsequently, can result in preterm birth. This review is focused on the role of dNK cells in normal pregnancy and pathological pregnancy, including preeclampsia, recurrent spontaneous abortion, endometriosis, and recurrent implantation failure. dNK cells could be targets for the treatment of pregnancy complications.

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“…[14] RM was also attributed to other immunological mechanisms such as the hyperactivity of natural killer cells and the imbalance of T-helper (Th) 1 and Th2 responses consisting of a predominant Th1 response. Low concentrations of CD4 + CD25 + FoxP3 + regulatory T cells have also been considered an RM risk factor [[15], [16], [17], [18]].…”

Section: Introductionmentioning

confidence: 99%

Gestational and perinatal outcomes in recurrent miscarriages couples treated with lymphocyte immunotherapy

Sarno

Cavalcante

Niag

et al. 2019

European Journal of Obstetrics & Gynecology and Reproductiv

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Objective This study aims to elucidate which types of recurrent miscarriage (RM) patients experienced a livebirth after paternal lymphocyte immunotherapy (LIT) and to evaluate the perinatal outcome. Study design Retrospective analysis of a multicenter, observational study which enrolled 1096 couples with a history of two or more spontaneous miscarriages without any intercalated delivery. We conducted an intention-to-treat analysis of couples with RM treated with or without LIT regarding to gestational and perinatal outcomes. We compared groups by using the Student’s t -test or Kruskal–Wallis test, Fisher’s exac t -test and χ 2 test when appropriate. Results The success of gestation was significantly higher in the LIT group (60.1% vs. 33.1%; p < 0.001). A sub-analysis of four different immune disorder groups revealed a significantly higher success in the LIT group in all immune categories, except in patients who had autoantibodies positive. We observed no significant differences in perinatal outcomes such as gestational age at birth, preterm and extreme preterm birth, and birth weight in successful pregnancy in both groups. The success rate was significantly higher when LIT was administrated before and during pregnancy and only during pregnancy compared to only before pregnancy ( p < 0.01). Conclusions Careful laboratory test phenotyping of RM patients may identify subgroups most likely to benefit and exclude those with little likelihood of benefit, and LIT during a pregnancy may significantly improve success rates.

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Natural killer cell activity in women with recurrent miscarriage: Etiology and pregnancy outcome

Cited by 23 publications

References 26 publications

Single-cell immune landscape of human recurrent spontaneous abortion

Single-cell immune landscape of human recurrent spontaneous abortion

Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications

Gestational and perinatal outcomes in recurrent miscarriages couples treated with lymphocyte immunotherapy

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