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nk cell miscarriage

Ângela C Crespo, Jack L Strominger, Tamara Tilburgs
The combination of the activating killer cell Ig-like receptor 2DS1 (KIR2DS1) expressed by maternal decidual natural killer cells (dNK) and the presence of its ligand, the HLA-C allotype HLA-C2, expressed by fetal trophoblasts, reduces the risk of developing pregnancy complications. However, no molecular or cellular mechanism explains this genetic correlation. Here we demonstrate that KIR2DS1+ dNK acquired higher cytotoxic function than KIR2DS1- dNK when exposed to human cytomegalovirus (HCMV)-infected decidual stromal cells (DSC), particularly when DSCs express HLA-C2...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
R J Kuon, K Vomstein, M Weber, F Müller, C Seitz, S Wallwiener, T Strowitzki, E Schleussner, U R Markert, V Daniel, B Toth
Peripheral and uterine NK cells (pNK, uNK) can be distinguished according to their receptor expression. Recent studies indicate an association of elevated pNK and uNK with recurrent miscarriage (RM). This study aimed to analyze pNK and uNK in patients with RM and healthy controls. Out of n=590 RM patients screened according to a standard diagnostic protocol, n=268 couples with ≥3 consecutive RM were identified. Subgroups consisted of n=151 primary RM (pRM), n=85 secondary RM (sRM), n=32 tertiary RM (tRM) and n=42 healthy controls...
November 6, 2016: Journal of Reproductive Immunology
Yu-Han Meng, Xiao-Hui Zhu, Li-Ying Yan, Yan Zhang, Hong-Yan Jin, Xi Xia, Rong Li, Jie Qiao
INTRODUCTION: The successful pregnancy depends on maternal immune tolerance against the fetus. It has been reported that MSCs (mesenchymal stem cells) could play a regulatory role on immune cells such as CD4(+)T cells, macrophages and NK cells, but their effect on recurrent miscarriage is unknown. STUDY DESIGN: In a prospective study, the abortion-prone (CBA/J × DBA/2) H-2(d) × H-2(k) mice were utilized. Female CBA/J mice (8-10 weeks old) were injected with vehicle or MSCs via tail vein or uterine horns, and 14 days later, they were mated with DBA/2 males for the following experiments...
November 2016: Placenta
Vahid Davoudi, Kiandokht Keyhanian, Riley M Bove, Tanuja Chitnis
Anti-aquaporin-4 (AQP4) autoantibody plays a key role in the pathogenesis of neuromyelitis optica (NMO). Studies have shown increased relapse rates in patients with NMO during pregnancy and postpartum. High estrogen levels during pregnancy can increase activation-induced cytidine deaminase expression, which is responsible for immunoglobulin production. Additionally, sex hormones may influence antibody glycosylation, with effects on antibody function. Estrogen decreases apoptosis of self-reactive B cells, through upregulation of antiapoptotic molecules...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
N M Mamedalieva, A M Kurmanova, G N Moshkalova, V Kim
A study of the endometrium of women with herpetic infection has shown that early miscarriages (under 12 weeks) occurs as activation of cytotoxic natural killer (NK) cells with CD16 + phenotype and a pronounced suppression level of CD56 + cells endometrial type, and late miscarriages (13-22 weeks of gestation) occurs as cell deficit, followed by reduction of all CD8 + cytotoxic lymphocytes, and of CD56 + and CD16 + NK cells.
October 2016: Gynecological Endocrinology
Xian Chen, Biao Yin, Ruo-Chun Lian, Tao Zhang, Hong-Zhan Zhang, Liang-Hui Diao, Yu-Ye Li, Chun-Yu Huang, De-Sheng Liang, Yong Zeng
PROBLEM: We aimed to investigate the modulatory effects of vitamin D on peripheral blood cellular immune response in patients with recurrent miscarriage (RM). METHOD OF STUDY: The effect of vitamin D on the number of peripheral blood cells, T helper 1 (Th1) cytokines, and NK cytotoxicity was measured in 99 women with RM. RESULTS: The percentage of CD19(+) B cells and NK cytotoxicity at an effector-to-target cell (E:T) ratio of 50:1, 25:1, and 12...
December 2016: American Journal of Reproductive Immunology: AJRI
Gi Su Lee, Joon Cheol Park, Jeong Ho Rhee, Jong In Kim
OBJECTIVE: The 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. METHODS: One 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...
September 2016: Obstetrics & Gynecology Science
L V Krechetova, V V Vtorushina, M A Nikolaeva, E L Golubeva, L V Van'ko, V A Saribegova, N K Tetruashvili
We studied the expression of an early activation marker CD69 in peripheral blood lymphocytes of pregnant women with a history of recurrent pregnancy loss after immunization with paternal lymphocytes. Spontaneous and phytohemagglutinin-stimulated expression of CD69 on the surface of T cells and NK cells isolated from the peripheral blood was analyzed. On gestation week 5-6, the number of T cells expressing CD69 spontaneously and after stimulation was significantly higher in women with miscarriage than in woman with prolonged pregnancy...
August 2016: Bulletin of Experimental Biology and Medicine
Xiao-Rui Liu, Yu-Na Guo, Chuan-Mei Qin, Xiao-Li Qin, Fei Tao, Fei Su, Fu-Ju Tian, Yan Zhang, Yi Lin
Intrauterine infection is one of the most frequent causes of miscarriage. CpG oligodeoxynucleotide (CpG ODN) can mimic intrauterine infection. CpG ODN-induced embryo-resorption was observed consistently in the NK-cell deficient non-obese diabetic (NOD) mice but not in the wild-type (WT) mice. To elucidate the molecular mechanisms of differential pregnancy outcomes, differentially expressed genes (DEGs) in the placenta and decidua basalis was revealed by RNA-Seq with CpG ODN or control ODN treatment. Common DEGs in the WT and NOD mice were enriched in antimicrobial/antibacterial humoral responses that may be activated as a primary response to bacterial infection...
August 5, 2016: International Journal of Molecular Sciences
Shigeru Saito, Yasushi Nakabayashi, Akitoshi Nakashima, Tomoko Shima, Osamu Yoshino
The fetus is a semi-allograft for the maternal host in natural pregnancy, but the fetus is a complete allograft after oocyte donation (OD), and there is greater antigenic dissimilarity with the mother. Thus, OD pregnancy is a good model for understanding how the fetus is protected by the maternal immune system. Recent clinical data have revealed a higher risk of miscarriage, gestational hypertension, preterm birth, and low birth weight with OD pregnancy. There is also a higher incidence of chorionic deciduitis, dense fibrinoid deposits in the chorionic basal plate, inflammatory lesions in the chorionic plate, and C4d deposition on syncytiotrophoblasts in OD pregnancy...
June 20, 2016: Seminars in Immunopathology
Tamara Gulic, Gordana Laskarin, Marin Dominovic, Lana Glavan Gacanin, Emina Babarovic, Herman Haller, Daniel Rukavina
PROBLEM: The role of HSP70 and both its constitutive (Hsc) and inducible (Hsp) forms in the pathogenesis of threatened spontaneous abortions was investigated. METHOD OF STUDY: Immunohistology and/or immunofluorescence was used to analyze paraffin-embedded tissue sections, and reverse transcriptase-quantitative polymerase chain reaction and flow cytometry were used for analyses of decidual mononuclear cells (DMCs) and confocal microscopy for the detection of perforin, granulysin, and lysosome-associated membrane protein-1 (LAMP-1) in decidual lymphocytes (DLs)...
August 2016: American Journal of Reproductive Immunology: AJRI
Gendie E Lash, Judith N Bulmer, Tin Chiu Li, Barbara A Innes, Najat Mariee, Gnyaneshwari Patel, Jean Sanderson, Siobhan Quenby, Susan M Laird
Considerable work is being carried out on endometrial NK cells to determine whether they play a role in successful pregnancy outcome. In addition there is debate about whether measurements of uNK should be included in the clinical assessment for women with recurrent implantation failure or recurrent miscarriage. A hindrance to taking this forward is the fact that the density of uNK cells reported by different centres is very different. The aim of this study was to determine the reason for these differences and to develop a standardised method...
August 2016: Journal of Reproductive Immunology
Tomoko Ichikawa, Yasuyuki Negishi, Masumi Shimizu, Toshiyuki Takeshita, Hidemi Takahashi
Innate immunity, which is unable to discriminate self from allo-antigens, is thought to be important players in the induction of miscarriages. Here, we show that the administration of IL-12 to syngeneic-mated C57BL/6 mice on gestation day 7.5 (Gd 7.5), drives significant miscarriages in pregnant females. Furthermore, the administration on Gd 7.5 of α-galactosylceramide (α-GalCer), which is known to activate invariant natural killer T (iNKT) cells, induced miscarriages in both syngeneic-mated C57BL/6 mice and allogeneic-mated mice (C57BL/6 (♀) × BALB/c (♂))...
August 2016: European Journal of Immunology
Terhi T Piltonen
Women with polycystic ovarian syndrome (PCOS) present with several endometrial abnormalities possibly explaining some of the adverse endometrium-related outcomes in these women. PCOS and an increased miscarriage rate have been suggested to coincide, but the results are conflicting. Recent studies have also shown increased risks of pregnancy-induced hypertension, preeclampsia, and premature delivery that may be related to altered decidualization/placentation in affected women. In the long run, PCOS per se is associated with the occurrence of endometrial cancer (EC), with obesity aggravating the risk...
November 2016: Best Practice & Research. Clinical Obstetrics & Gynaecology
J H Check, D L Check
PURPOSE: To evaluate the efficacy of intralipid intravenous infusion in achieving a live pregnancy following IVF--embryo transfer in women of advanced reproductive age (40-42 years). MATERIALS AND METHODS: A matched control was performed. Women aged 40-42 with a previous history of miscarriage or who failed to conceive despite previous embryo transfer who entered an IVF program were offered intravenous intralipid therapy (four ml of 20% liposyn II in 100 ml normal saline over one hour) during the mid-follicular phase...
2016: Clinical and Experimental Obstetrics & Gynecology
Mohamed M Farghali, Abdel-Latif G El-Kholy, Khaled H Swidan, Ibrahim A Abdelazim, Ahmed R Rashed, Ezzat El-Sobky, Mostafa F Goma
OBJECTIVE: To evaluate the relation between uterine killer (uK) cells and unexplained repeated miscarriage (RM). MATERIAL AND METHODS: Eighty women with unexplained repeated miscarriage and missed miscarriage of current pregnancy were studied. Fetal viability and gestational age of the current pregnancy were confirmed by ultrasound, followed by suction evacuation to collect abortion specimens and uterine wall curettage to collect decidua specimens. Abortion specimens were collected for long-term monolayer cell culture and subsequent chromosome analysis using conventional G-banding...
2015: Journal of the Turkish German Gynecological Association
Howard J A Carp
Progestational agents are often prescribed to prevent threatened miscarriage progressing to miscarriage, and subsequent miscarriages in recurrent pregnancy loss. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. A recent Cochrane review reported that progestogens were effective for treating threatened miscarriage with no harmful effects on mother or fetus. The results were not statistically different when vaginal progesterone was compared to placebo, (RR=0...
August 1, 2016: Hormone Molecular Biology and Clinical Investigation
Fatma Eskicioğlu, Alper Tunga Özdemir, Rabia Bilge Özdemir, Gülüzar Arzu Turan, Zafer Akan, Solmaz Pınar Hasdemir
OBJECTIVE: To determine role of human leukocyte antigen (HLA)-G, CD8, CD16, CD56, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α for recurrent miscarriages in feto-maternal interface. METHOD: Chorion and decidua samples were obtained from 11 women with unwanted pregnancies (healthy pregnancy, HP) and 10 women with missed abortion diagnosis after at least two pregnancy losses (recurrent miscarriage, RM). In addition, endometrial tissues were obtained from 10 non-pregnant women (NonP)...
September 2016: Journal of Maternal-fetal & Neonatal Medicine
Sung Ki Lee, Jee Yun Kim, Ae Ra Han, Sung Eun Hur, Chul Jung Kim, Tae Hyun Kim, Bo Ra Cho, Jae Won Han, Sae Geul Han, Baeg Ju Na, Joanne Kwak-Kim
PROBLEM: We investigated the therapeutic effect of intravenous immunoglobulin (IVIG) in women with recurrent pregnancy loss (RPL). METHOD OF STUDY: This was a retrospective observational study. Total 189 RPL women who experienced ≥2 miscarriages were enrolled and investigated conventional etiologies, thrombophilia, and cellular immunity. Patients were divided into four groups; known etiology with (Gr1) and without cellular immune abnormality (Gr2), unknown etiology with (Gr3) and without cellular immune abnormality (Gr4)...
January 2016: American Journal of Reproductive Immunology: AJRI
Sourima Biswas Shivhare, Judith N Bulmer, Barbara A Innes, Dharani K Hapangama, Gendie E Lash
Heavy menstrual bleeding (HMB) affects 30% of women of reproductive age and significantly interferes with quality of life. Altered endometrial vascular maturation has been reported in HMB and recurrent miscarriage, the latter associated with increased uterine natural killer (uNK) cell numbers. This study compared endometrial leukocyte populations in controls and women with HMB. Formalin-fixed paraffin-embedded endometrial biopsies from controls (without endometrial pathology) and HMB were immunostained for CD14 (macrophages), CD56 (uNK cells), CD83 (dendritic cells), FOXP3 (regulatory T cells/Tregs), CD3 and CD8 (T cells)...
November 2015: Journal of Reproductive Immunology
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