Concordance between peripheral and decidual NK cell subsets and killer immunoglobulin-like receptors in women with recurrent spontaneous miscarriages (original) (raw)
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American Journal of Reproductive Immunology, 2009
Problem Natural killer (NK) cells are regulated through NK cell receptors such as killer cell immunoglobulin-like receptors (KIRs). KIRs are suspected of being involved in the causes of recurrent miscarriage (RM) as a higher proportion of activated NK cells were observed in women with RM when compared with that in controls. The aim of this study was to investigate if KIR genes coding for receptors known to have as ligands HLA class I molecules are correlated with RM.Method of study A matched case–control study was carried out in 68 south Brazilian Caucasian patient couples with RM and 68 control fertile couples. KIR genes were typed by PCR-Reverse SSO method.Results The rate of possession of an elevated number of activating KIR genes (positive for five or six activating KIR genes out of six different activating KIR genes analyzed) in RM patient women was significantly higher (P = 0.0201) when compared with that in control fertile women. These data suggest that women carrying a high content of activating KIR genes have about threefold increased probability to develop RM [OR = 2.71; 95% CI (1.23–6.01)].Conclusion Our results indicate that RM could be associated with NK cell activation mediated by a profile rich in activating KIR genes.
Natural killer cells in recurrent miscarriage: An overview
Journal of Reproductive Immunology, 2020
Recurrent Miscarriage is an early pregnancy complication which affects about 1-3 % of child-bearing couples. The mechanisms involved in the occurrence of recurrent miscarriages are not clearly understood. In the last decade Natural Killer cells have been studied in peripheral blood and uterus in order to determine if there are specific characteristics of Natural Killer cells associated with miscarriage. Different authors have described an increased number of uterine and peripheral blood Natural Killer cells in women with recurrent miscarriages compared to control women. However, its relationship with miscarriage has not been confirmed. In patients with recurrent miscarriage a lack of inhibition of decidua Natural Killer cells can be observed, which leads to a more activated state characterized by higher levels of proinflammatory cytokines. In peripheral blood, it has been also reported a dysfunctional cytokine production by Natural Killer cells, with an increase of interferon-γ levels and a decrease of Interleukin-4. Significant progress has been made in the last decade in understanding the biology of Natural Killer cells, including the identification of new receptors that also contribute to the activation and regulation of Natural Killer cells. In this review, we summarize the current progress in the study of Natural Killer cells in recurrent miscarriage.
International Journal of Pregnancy & Child Birth, 2018
Around 50% of recurrent spontaneous abortions (RSA) remain unexplained. Immunological etiology has been proposed, supported by evidence of lower count of natural killer (NK) cells in peripheral blood of RSA women compared to women with normal delivery history. However, studies concerning the cytotoxic activity of NK cells in women with RSA are still controversial. We performed an observational casecontrol study assaying peripheral blood NK (pNK) cells cytotoxic activity in nonpregnant RSA women compared to non-pregnant women with normal delivery history. Twelve RSA and nine control women were recruited and blood samples were drawn during the luteal phase of ovarian cycle. pNK cells were incubated with target CFSElabeled K562 cells and cytotoxicity was measured by cytofluorimetry. In non-pregnant RSA women pNK cytotoxic activity was not significantly altered compared to control women.In luteal phase of ovarian cycle the level of cytotoxic activity of pNK cells is not a marker for predicting RSA, and clinicians should not use pNK activity as a systematic recurrent pregnancy loss examination.
Journal of Clinical Medicine
Immune tolerance at the feto-maternal interface is crucial for the growth of the semi-allograft fetus in the womb. The outcome of pregnancy is dependent on a fine balance between various immunological forces. For a long time, the potential role of the immune system in pregnancy disorders has remained enigmatic. Current evidence has revealed that natural killer (NK) cells are the predominant immune cell population in the uterine decidua. NK cells cooperate with T-cells to provide an optimal microenvironment for the growth of the developing fetus by producing cytokines, chemokines, and angiogenic factors. These factors support trophoblast migration and angiogenesis which regulates the process of placentation. NK cells differentiate between “self” and “non-self” through their surface receptors known as killer-cell immunoglobulin-like receptors (KIRs). They induce immune tolerance through communication via their KIR and fetal human leucocyte antigens (HLA). KIRs are surface receptors of...
Journal of Reproductive Immunology, 2014
Natural killer (NK) cells play fundamental function in maintaining pregnancy. Based on the availability and non-invasive method of collection of menstrual blood (MB), here we investigated for the first time comparative analysis of NK cell subsets in MB and peripheral blood (PB) of recurrent spontaneous abortion (RSA) and fertile women. PB and MB of healthy fertile (n=15) and RSA women (n=15) were sampled simultaneously in the second day of menstrual cycle. Frequency of CD56+CD3-CD16+/-, CD56+CD3-CCR7+/-, and CD56+CD3-CD45RO+/-cells was analyzed by flow cytometry. In MB of both groups, CD16+ and CD45RO-NK cells were significantly lower compared to PB. In parallel, CD56+CD16+CCR7-and CCR7+ cells were present at significantly lower frequencies in MB than PB. However, the frequencies of CD56+CD16-CCR7-and CCR7+ cells were higher in MB. In comparison to fertile group, percentage of MB CD45RO+ NK cells was significantly lower and frequencies of PB CD16-, CD45RO-and CD56+CD16+CCR7+ subsets were significantly higher in RSA patients. Different subsets of NK cells are differentially distributed in MB in comparison with PB in RSA and fertile subjects. Population differences of NK cell subsets in RSA patients and normal controls were more reflected at the systemic level.