Elevated natural killer cell levels and autoimmunity synergistically decrease uterine blood flow during early pregnancy

Yi, Hyun Jeong; Kim, Jung Hyun; Koo, Hwa Seon; Bae, Ju Youn; Wha, Sun; Yang, Kwang Moon

doi:10.5468/ogs.2014.57.3.208

Cited by 9 publications

(5 citation statements)

References 29 publications

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“…Uterine natural killer cells in the endometrium are thought to support remodeling of the uterine spiral arteries and to facilitate successful placentation through the regulation of trophoblast invasion. An abnormal increase of the peripheral blood natural killer cell fraction and NK cytolytic activity is associated with RPL [ 21 22 ]. Downregulation of NK cells was associated with a favorable pregnancy outcome [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Etiologic characteristics and index pregnancy outcomes of recurrent pregnancy losses in Korean women

et al. 2016

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ObjectiveThe goal of this study was to evaluate the etiologies and clinical outcomes of Korean recurrent pregnancy loss (RPL) patients. And also, we investigated the differences between primary and secondary RPL patients, between two and three or more pregnancy losses.MethodsOne hundred seventy eight women diagnosed as RPL were enrolled. We performed chromosomal analysis, thyroid stimulating hormone, prolactin, blood glucose, plasminogen activator inhibitor-1, natural killer cell proportion, anticardiolipin antibodies, antiphospholipid antibodies, lupus anticoagulant, anti-β2glycoprotein-1 antibodies, antinuclear antibody, protein C, protein S, antithrombin III, homocysteine, MTFHR gene, factor V Leiden mutation, and hysterosalphingography/hysteroscopic evaluation.ResultsThe mean age was 34.03±4.30 years, and mean number of miscarriages was 2.69±1.11 (range, 2 to 11). Anatomical cause (13.5%), chromosomal abnormalities (5.6%), and endocrine disorders (34.3%) were observed in RPL women. Elevated natural killer cell and antiphospholipid antibodies were observed in 43.3% and 7.3% each. Among of 178 women, 77 women were pregnant. After management of those women, live birth rate was 84.4% and mean gestational weeks was 37.63±5.12. Women with three or more RPL compared with women with two RPL had more common anatomical cause such as intrauterine adhesions and lower rates of spontaneous pregnancy. Compare with secondary RPL women, immunological abnormalities were more common in primary RPL. However, miscarriage rates were not different.ConclusionImmunological factor including autoimmune and alloimmune disorders was most common etiology of RPL. Inherited thrombophilia showed different patterns with other ethnic countries. Miscarriage rates were not different between primary and secondary RPL, or between two and three or more miscarriages group.

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Section: Discussionmentioning

confidence: 99%

Etiologic characteristics and index pregnancy outcomes of recurrent pregnancy losses in Korean women

et al. 2016

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“…[45][46][47][48][49] Concerning the relationship between autoimmunity and NK cells in human reproduction, the uterine blood flow is an innovative method recently suggested in the evaluation of the role of NK cells, that would be of interest in order to predict the risk of recurrent miscarriage and to measure the effects of treatment in women with infertility/RSA. 50,51 We should consider that the present study suffers from several limitations:…”

Section: Discussionmentioning

confidence: 99%

Peripheral blood natural killer cells and mild thyroid abnormalities in women with reproductive failure

Triggianese

Perricone

Conigliaro

et al. 2015

Int J Immunopathol Pharmacol

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Abnormalities in peripheral blood natural killer (NK) cells have been reported in women with primary infertility and recurrent spontaneous abortion (RSA) and several studies have been presented to define cutoff values for abnormal peripheral blood NK cell levels in this context. Elevated levels of NK cells were observed in infertile/RSA women in the presence of thyroid autoimmunity (TAI), while no studies have been carried out, to date, on NK cells in infertile/ RSA women with non-autoimmune thyroid diseases. The contribution of this study is two-fold: (1) the evaluation of peripheral blood NK cell levels in a cohort of infertile/RSA women, in order to confirm related data from the literature; and (2) the assessment of NK cell levels in the presence of both TAI and subclinical hypothyroidism (SCH) in order to explore the possibility that the association between NK cells and thyroid function is not only restricted to TAI but also to SCH. In a retrospective study, 259 age-matched women (primary infertility [n = 49], primary RSA [n = 145], and secondary RSA [n = 65]) were evaluated for CD56+CD16+NK cells by flow cytometry. Women were stratified according to thyroid status: TAI, SCH, and without thyroid diseases (ET). Fertile women (n = 45) were used as controls. Infertile/RSA women showed higher mean NK cell levels than controls. The cutoff value determining the abnormal NK cell levels resulted ⩾15% in all the groups of women. Among the infertile/RSA women, SCH resulted the most frequently associated thyroid disorder while no difference resulted in the prevalence of TAI and ET women between patients and controls. A higher prevalence of women with NK cell levels ⩾15% was observed in infertile/RSA women with SCH when compared to TAI/ET women. According to our data, NK cell assessment could be used as a diagnostic tool in women with reproductive failure and we suggest that the possible association between NK cell levels and thyroid function can be described not only in the presence of TAI but also in the presence of non-autoimmune thyroid disorders.

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“…For instance, in women with Hashimoto’s thyroiditis, Th1 cells actively involve the inflammatory lymphocyte infiltration of the exocrine glands and epithelia and cause subsequent thyroiditis, glandular damages, and apoptosis of thyroid cells ( 71 ). Moreover, Th1 cells are also recruited to the endometrium, decidua, and placenta, and activate NK cells, resulting in spontaneous abortion ( 72 ). Therefore, Th1 immunity, a shared underlying immunopathology, induces RPL in women with autoimmune diseases.…”

Section: Th1 Immunity For Controlled Inflammation During Implantationmentioning

confidence: 99%

T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells

et al. 2020

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During pregnancy, various immune effectors and molecules participating in the immunemicroenvironment establish specific maternal tolerance toward the semi-allogeneic fetus. Activated maternal immune effectors by the trophoblast antigens, such as T helper (Th), T cytotoxic (Tc), T regulatory (Treg), and B cells, are involved in the regulation of adaptive immunity. Recognition of active signal through the T cell receptors stimulate the differentiation of naive CD3 + CD4 + T cells into specific T cell subsets, such as Th1, Th2, Th9, Th17, Th22, and follicular Th cells (Tfh). Each of these subsets has a significant and distinct role in human pregnancy. Th1 immunity, characterized by immune-inflammatory responses, becomes dominant during the peri-implantation period, and the "controlled" Th1 immunity benefits the invading trophoblasts rather than harm. Quickly after the placental implantation, the early inflammatory Th1 immunity is shifted to the Th2 antiinflammatory immune responses. The predominant Th2 immunity, which overrules the Th1 immunity at the placental implantation site, protects a fetus by balancing Th1 immunity and accommodate fetal and placental development. Moreover, Treg and Th9 cells regulate local inflammatory immune responses, potentially detrimental to the fetus. Th17 cells induce protective immunity against extracellular microbes during pregnancy. However, excessive Th17 immunity may induce uncontrolled neutrophil infiltration at the maternal-fetal interface. Other Th cell subsets such as Tfh cells, also contribute to pregnancy by setting up favorable humoral immunity during pregnancy. However, dysregulation of Th cell immunity during pregnancy may result in obstetrical complications, such as recurrent pregnancy losses (RPL) and preeclampsia (PE). With this review, we intend to deliver a comprehensive overview of CD4 + Th cell subsets, including Th1, Th2, Th9, Th17, Th22, and Tfh cells, in human pregnancy by reviewing their roles in normal and pathological pregnancies.

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Elevated natural killer cell levels and autoimmunity synergistically decrease uterine blood flow during early pregnancy

Cited by 9 publications

References 29 publications

Etiologic characteristics and index pregnancy outcomes of recurrent pregnancy losses in Korean women

Etiologic characteristics and index pregnancy outcomes of recurrent pregnancy losses in Korean women

Peripheral blood natural killer cells and mild thyroid abnormalities in women with reproductive failure

T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells

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