Article

Natural killer cells, miscarriage, and infertility

Department of Pathology, University of Cambridge, Cambridge CB2 1QP.
BMJ (online) (Impact Factor: 16.38). 12/2004; 329(7477):1283-5. DOI: 10.1136/bmj.329.7477.1283
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    • "It may be assumed that in favorable immune phenotype the function of immune system improves as a whole, i.e., the processes of migration of immunocompetent cells are more correct in both their quantity and quality, especially those of natural killers, into organs of the reproductive system on the basis of optimized cytokine regulation that creates optimal conditions for relatively autonomic regulation in the reproductive system. Phenotypically and functionally decidual NK cells are different from NK cells in peripheral blood and may be regarded as a separate lymphoid subset [30]. Migration of peripheral NK cells through the human endothelial and stromal decidual cells is possible because of chemokines support [31]. "
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    ABSTRACT: Immune markers that may predict IVF failure and successful implantation and pregnancy were studied. Favorable immune parameters were selected based on 90% of data of women who got pregnant and had uneventful pregnancy course and outcome in present IVF cycle. Immune phenotype and NK cell activity of peripheral blood of 123 women with multiple IVF failure were studied by flow cytometry. Some parameters that were out of favorable borders (elevated expression of CD56, CD158a in T lymphocytes, decreased levels of CD4 T lymphocytes, up-regulated expression of HLA DR in CD8+ T cells and NK cells, elevated number of NK cells and increased NK cytotoxicity, increased and decreased expression of CD158a and CD8 in NK cells) were considered to be immune deviations (ID) potentially predictive for IVF failure. In women with 0-1 ID implantation rate (IR) was 50.9% (27/53), with two ID - 42.8% (12/28), with three and more ID - 21.4% (9/42). IR in group with three ID was lower than in group with 0-1 ID (p<0.01, OR=3.8, CI: 1.52-9.48) and in group with two ID (p<0.05). Live birth rate (LBR) in women with 0-1 ID was 33.9%, with two ID - 28.5%, with three and more ID - 9.5%. LBR in group with three ID was lower than in group with 0-1 ID (p<0.01, OR=4.8, CI: 1.52-15.8) and in group with two ID (p<0.05). The absence or single ID seems to be more favorable for successful IVF program. Combination of ID may predict implantation failure to a greater degree than isolated ID. Multiple immune deviations form unfavorable "immune phenotype" for implantation and pregnancy development. Copyright © 2014. Published by Elsevier B.V. KEYWORDS: Favorable immune phenotype; IVF; Implantation; Pregnancy
    Immunology Letters 10/2014; 162(2). DOI:10.1016/j.imlet.2014.10.022 · 2.37 Impact Factor
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    • "NK cells are the predominant lymphocyte population present in the uterus (King, 1991, 1996; Whitelaw, 1996; Moffett et al., 2004; Croy et al., 2006, Quenby and Farquharson, 2006). "
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    ABSTRACT: Uterine natural killer (uNK) cells represent the predominant lymphocytes in the uterus during early pregnancy and in the secretory phase of the menstrual cycle. They are CD56(high)CD16(-) and have low cytotoxicity, but constitutively secrete a number of cytokines, chemokines and angiogenic molecules. uNK cells differ from CD56(high) blood NK cells in several ways, including the killer cell immunoglobulin-like receptor repertoire and expression of some genes induced by hormone environment. uNK cells may arise by in-utero proliferation and differentiation of NK cell progenitors under the control of the sex steroid hormones and/or cytokines, such as interleukin-15, and/or be recruited from CD56(+) blood NK cells that would undergo tissue-specific differentiation in the uterine microenvironment. There is evidence showing that uNK cells display a different pattern of chemokine receptors and adhesion molecules, thus leading to a different migratory response. It has not yet been fully defined which uNK cell function(s) are critical for successful pregnancy. The close encirclement of spiral arteries by NK cells, together with their ability to produce angiogenic factors, suggests that they might influence mucosal vascularization. Their proximity to the extravillous trophoblast supports the idea that uNK cells could recognize these cells as fetal, and regulate their invasion during placentation.
    Reproductive biomedicine online 03/2008; 16(2):202-10. DOI:10.1016/S1472-6483(10)60575-5 · 2.98 Impact Factor
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    • "NK cells are also found in the endometrium and decidua, but the knowledge on their role in human placentation is limited. There are phenotypic and functional differences between peripheral and uterine NK cells, and tests to measure NK cells in peripheral blood give no useful information on uterine NK cells (Moffett et al., 2004). Furthermore, the percentage of CD56+ NK cells in peripheral blood of healthy individual varies from 5 to 29% and is affected by sex, stress, ethnicity and age. "
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    ABSTRACT: Recurrent miscarriage (RM; > or =3 consecutive early pregnancy losses) affects around 1% of fertile couples. Parental chromosomal anomalies, maternal thrombophilic disorders and structural uterine anomalies have been directly associated with recurrent miscarriage; however, in the vast majority of cases the pathophysiology remains unknown. We have updated the ESHRE Special Interest Group for Early Pregnancy (SIGEP) protocol for the investigation and medical management of RM. Based on the data of recently published large randomized controlled trials (RCTs) and meta-analyses, we recommend that basic investigations of a couple presenting with recurrent miscarriage should include obstetric and family history, age, BMI and exposure to toxins, full blood count, antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies), parental karyotype, pelvic ultrasound and/or hysterosalpingogram. Other investigations should be limited to particular cases and/or used within research programmes. Tender loving care and health advice are the only interventions that do not require more RCTs. All other proposed therapies, which require more investigations, are of no proven benefit or are associated with more harm than good.
    Human Reproduction 10/2006; 21(9):2216-22. DOI:10.1093/humrep/del150 · 4.59 Impact Factor
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