scholarly journals Beyond Uterine Natural Killer Cell Numbers in Unexplained Recurrent Pregnancy Loss: Combined Analysis of CD45, CD56, CD16, CD57, and CD138

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 650 ◽  
Author(s):  
Maia Chiokadze ◽  
Christin Bär ◽  
Jana Pastuschek ◽  
Boris V. Dons’koi ◽  
Kseniia G. Khazhylenko ◽  
...  
Keyword(s):  
Natural Killer ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Plasma Cells ◽  
Immune Cell ◽  
Killer Cell ◽  
Cell Counts ◽  
Unk Cells ◽  
Uterine Natural Killer

Changes in the number and cytotoxic potential of uterine Natural Killer (uNK) cells have been associated with reduced fertility. To provide a better characterization of immunophenotypes in the endometrium of women with uRPL (unexplained recurrent pregnancy loss), we examined the applicability of a set of five immune cell markers. The concentration (cells/mm2) of CD45+ leukocytes, CD56+ uNK cells, and CD138+ plasma cells as well as of CD16+ and CD57+ cells, which indicate high cytotoxic uNK cells, were assessed by immunohistochemistry in endometrial biopsies from 61 uRPL patients and 10 controls. Control fertile endometria presented 90–300 CD56+ uNK cells/mm2. uRPL cases were classified in subgroups of low (uRPL-CD56low < 90 cells/mm2), normal (uRPL-CD56normal 90–300 cells/mm2), and high uNK cell counts (uRPL-CD56high > 300 cells/mm2). Some cases from the uRPL-CD56low and uRPL-CD56normal subgroups showed elevated proportions of cytotoxic CD16+ and CD57+ cells in relation to CD56+ cells. In the uRPL-CD56high subgroup, the CD57/CD56 ratio was reduced in most samples and the CD16/CD56 ratio was unaltered. Analysis of CD138 excluded the influence of chronic endometritis on these observations. Our results reinforce a link between uRPL and a dysfunctional endometrial environment associated with distinct immune cell profiles.

scholarly journals Are uterine natural killer and plasma cells in infertility patients associated with endometriosis, repeated implantation failure, or recurrent pregnancy loss?

2020 ◽  
Vol 302 (6) ◽  
pp. 1487-1494
Author(s):  
Nadine Freitag ◽  
Sarah J. Pour ◽  
Tanja N. Fehm ◽  
Bettina Toth ◽  
Udo R. Markert ◽  
...  
Keyword(s):  
Natural Killer ◽  
Plasma Cells ◽  
Immune Cell ◽  
Control Group ◽  
Chronic Endometritis ◽  
Uterine Natural Killer Cells ◽  
Unk Cells ◽  
Endometrial Scratching ◽  
Infertility Patients ◽  
Uterine Natural Killer

Abstract Purpose Infertility is a debilitating situation that millions of women around the world suffer from, but the causal relationship between infertility and endometriosis is still unclear. We hypothesize that the immune cell populations of uterine natural killer cells (uNK) and plasma cells (PC) which define chronic endometritis could differ in patients with or without endometriosis and therefore be the link to endometriosis-associated infertility. Methods Our retrospective study includes 173 patients that underwent an endometrial scratching in the secretory phase of the menstrual cycle and subsequently immunohistochemical examination for uNK cells and PC. Sixty-seven patients were diagnosed with endometriosis, 106 served as the control cohort. Results The risk for an elevated number of uNK cells in women with endometriosis is not increased as compared to the control group. Our findings suggest that patients with endometriosis are 1.3 times more likely to have chronic endometritis (CE) as compared to those without and that the treatment with doxycycline might increase pregnancy rates. Endometriosis and an increased number of uNK cells seem to be unrelated. Conclusions In contrast to the lately published connection between endometriosis, infertility and increased uNK cells, we could not find any evidence that patients with endometriosis are more prone to elevated uterine uNK cells. Counting of PC in endometrial biopsies might be a new approach in the search of biomarkers for the nonsurgical diagnosis of endometriosis since our findings suggest a connection.

1.  Heme Oxygenase‐1 Enzyme Deficiency Affects Uterine Natural Killer Cell Function During Murine Pregnancy 

2017 ◽  
Author(s):  
Tracy Zhang
Keyword(s):  
Natural Killer ◽  
Heme Oxygenase ◽  
Cell Function ◽  
Recurrent Miscarriage ◽  
Embryo Implantation ◽  
Killer Cell ◽  
Implantation Site ◽  
Heme Oxygenase 1 ◽  
Unk Cells ◽  
Uterine Natural Killer

Recurrent miscarriage is a condition that affects 1% of all women, and rejection of the fetus by the mother's immune system is thought to be one of the underlying causes. The mechanisms of maternal tolerance vital to a successful pregnancy are not well understood; however, uterine natural killer (uNK) cells are implicated as they comprise over 70% of immune cells in the uterus during early pregnancy. Heme oxygenase‐1 (HO‐1) is an enzyme that is known to be immunosuppressive. Moreover, mice missing HO‐1 have extremely high abortion rates. This study is the first to analyze the effects of HO‐1 deficiency specifically on uNK cells. We posit that an absence of HO‐1 affects normal uNK cell‐mediated immunosuppression, and also possibly their ability to modify uterine spiral arteries supplying blood to the fetus. Our study analyzed embryos from mice lacking or deficient in HO‐1 on days 8, 10, and 12 of pregnancy. Both number of uNK cells and degree of vascularization were analyzed using immunohistochemistry staining. We observed a significantly higher number of uNK cells in one area of the embryo implantation site and a significantly lower number of cells in another, suggesting the uNK cells are failing to localize properly. Analysis of vascularization is currently ongoing. Since women with multiple miscarriages have been shown to down‐regulate HO‐1, confirmation that absence of HO‐1 leads to implantation site abnormalities could pave the way for future clinical treatments.  

Peripheral natural killer cell activity as a predictor of recurrent pregnancy loss: a large cohort study

2013 ◽  
Vol 100 (6) ◽  
pp. 1629-1634 ◽  
Author(s):  
Kinue Katano ◽  
Sadao Suzuki ◽  
Yasuhiko Ozaki ◽  
Nobuhiro Suzumori ◽  
Tamao Kitaori ◽  
...  
Keyword(s):  
Cohort Study ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Killer Cell Activity ◽  
Large Cohort Study

scholarly journals The Roles of Uterine Natural Killer (NK) Cells and KIR/HLA-C Combination in the Development of Preeclampsia: A Systematic Review

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiuhua Yang ◽  
Yahui Yang ◽  
Yiru Yuan ◽  
Lin Liu ◽  
Tao Meng
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Systemic Disease ◽  
Killer Cell ◽  
Inflammatory Factors ◽  
Placental Development ◽  
Multiple Organs ◽  
Unk Cells ◽  
Exact Etiology ◽  
Uterine Natural Killer

Preeclampsia (PE) is termed as a systemic disease that involves multiple organs; however, the exact etiology is still quite unclear. It is believed that the poor remodeling of uterine spiral arteries triggers PE, thereby causing failed placentation and producing inflammatory factors. The decline of blood flow results in lowering the nutrients and oxygen received by the fetus and augmenting the placental pressure in PE. Decidual immune cells, especially uterine natural killer (uNK) cells, are involved in the process of placentation. Decidual NK (dNK) cells significantly contribute to the vascular remodeling through the secretion of cytokines and angiogenic mediators in normal placental development. The abnormal activation of NK cells in both the peripheral blood and the decidua was counted among the causes leading to PE. The correlation existing between maternal killer cell immunoglobulin-like receptor (KIR) and HLA-C in trophoblast cells constitutes a robust evidence for the genetic etiology of PE. The combinations of the two kinds of gene systems, together with the KIR genotype in the mother and the HLA-C group in her fetus, are likely to exactly decide the pregnancy outcome. The women, who have the inappropriate match of KIR/HLA-C, are likely to be prone to the augmented risk of PE. However, the combinations of KIR/HLA-C in PE undergo ethnic changes. The extensive prospective research works in Europe, Asia, and Africa are required for providing more findings in PE patients.

scholarly journals Different Background: Natural Killer Cell Profiles in Secondary versus Primary Recurrent Pregnancy Loss

2021 ◽  
Vol 10 (2) ◽  
pp. 194
Author(s):  
Laura Strobel ◽  
Kilian Vomstein ◽  
Christiana Kyvelidou ◽  
Susanne Hofer-Tollinger ◽  
Katharina Feil ◽  
...  
Keyword(s):  
Natural Killer ◽  
Live Birth ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Nk Cell ◽  
Killer Cell ◽  
Activation Markers ◽  
Immune Alterations ◽  
Previous Live Birth ◽  
A Prospective Study

(1) Background: Prior studies suggested a significant impact of previous live births on peripheral natural killer cells (pNK) in patients with recurrent pregnancy loss (RPL). Patients with primary RPL (pRPL, no live birth) showed higher numbers of pNK than secondary RPL patients (sRPL, ≥ 1 live birth). (2) Methods: To further determine immunological differences between RPL patients and controls, we analysed pNK subpopulations and activation markers in pRPL (n = 47), sRPL (n = 24) and controls with previous live birth (sCtrl, n = 25) and nullipara (pCtrl, n = 60) within a prospective study. Percentages and numbers of CD56dimCD16bright cells, subpopulations and activation markers (CD57+, CD62L+, NKG2D+, NKp46+) were measured in non-pregnant RPL patients and n = 85 controls (n = 60 pCtrl, n = 25 sCtrl) in the mid-luteal phase by flow cytometry. (3) Results: Compared to sRPL patients, sCtrls showed higher CD56+ and CD56dimCD16bright numbers. Further, sRPL patients showed lower numbers of CD56dimCD16brightNKG2D+ and CD56dimCD16brightNKp46+ than sCtrls. (4) Conclusion: We suggest a chronic immune stimulation leading to a lower NK-cell count in sRPL patients with a lower NK cytotoxicity. This underlines the necessity to investigate pNK subpopulations as well as pRPL and sRPL separately to delineate the immune alterations in RPL.

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