Determination of Clinical Cellular Immune Markers in Women with Recurrent Pregnancy Loss

Lee, Sung Ki; Na, Baeg Ju; Kim, Jee Yun; Hur, Sung Eun; Lee, Millina; Gilman‐Sachs, Alice; Kwak‐Kim, Joanne

doi:10.1111/aji.12137

Cited by 73 publications

(110 citation statements)

References 56 publications

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“…Cluster #413 is probably an aggregate of monocytes and CD8 T cells. Previous studies have shown alterations in NK cell populations during pregnancy, particularly in association with different pregnancy outcomes 29, 30. The effects of pregnancy on circulating T cell populations are less known, although we and others have shown a subtle alteration of T cell cytokine patterns during pregnancy (31, 32, 33, and our data not shown).…”

Section: Resultssupporting

confidence: 38%

Competitive SWIFT cluster templates enhance detection of aging changes

Rebhahn

Roumanes

et al. 2015

Cytometry Pt A

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Clustering‐based algorithms for automated analysis of flow cytometry datasets have achieved more efficient and objective analysis than manual processing. Clustering organizes flow cytometry data into subpopulations with substantially homogenous characteristics but does not directly address the important problem of identifying the salient differences in subpopulations between subjects and groups. Here, we address this problem by augmenting SWIFT—a mixture model based clustering algorithm reported previously. First, we show that SWIFT clustering using a “template” mixture model, in which all subpopulations are represented, identifies small differences in cell numbers per subpopulation between samples. Second, we demonstrate that resolution of inter‐sample differences is increased by “competition” wherein a joint model is formed by combining the mixture model templates obtained from different groups. In the joint model, clusters from individual groups compete for the assignment of cells, sharpening differences between samples, particularly differences representing subpopulation shifts that are masked under clustering with a single template model. The benefit of competition was demonstrated first with a semisynthetic dataset obtained by deliberately shifting a known subpopulation within an actual flow cytometry sample. Single templates correctly identified changes in the number of cells in the subpopulation, but only the competition method detected small changes in median fluorescence. In further validation studies, competition identified a larger number of significantly altered subpopulations between young and elderly subjects. This enrichment was specific, because competition between templates from consensus male and female samples did not improve the detection of age‐related differences. Several changes between the young and elderly identified by SWIFT template competition were consistent with known alterations in the elderly, and additional altered subpopulations were also identified. Alternative algorithms detected far fewer significantly altered clusters. Thus SWIFT template competition is a powerful approach to sharpen comparisons between selected groups in flow cytometry datasets. © 2015 The Authors. Published Wiley Periodicals Inc.

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Section: Resultssupporting

confidence: 38%

Competitive SWIFT cluster templates enhance detection of aging changes

Rebhahn

Roumanes

et al. 2015

Cytometry Pt A

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“…Women with miscarriages and preeclampsia as well, have NK1 and NKT1 shift that produce high amounts of IFN-γ and little IL-4 in peripheral blood [11]. Therefore, cellular immune-regulation including innate immunity is critical for human reproduction.Women with RPL and MIF have significantly higher NK-cell levels and cytotoxicity, and dysregulated cytokine production patterns as compared to normal controls [10,12]. Activating receptor expression on NK cells was significantly increased, while inhibitory receptor expression was significantly decreased in vivo [13].…”

mentioning

confidence: 95%

“…Women with RPL and MIF have significantly higher NK-cell levels and cytotoxicity, and dysregulated cytokine production patterns as compared to normal controls [10,12]. Activating receptor expression on NK cells was significantly increased, while inhibitory receptor expression was significantly decreased in vivo [13].…”

mentioning

confidence: 95%

“…Additionally, decidual innate lymphoid cell 3 (ILC3) may play a role in innate defenses, and vessel and tissue rebuilding, thus contributing to maintenance of pregnancy [9]. Contrarily, a propensity to Th1 immune response and increased NK-cell levels and cytotoxicity have been reported in women with RPL and multiple implantation failures (MIF) after in vitro fertilization and embryo transfer cycles [10]. Women with miscarriages and preeclampsia as well, have NK1 and NKT1 shift that produce high amounts of IFN-γ and little IL-4 in peripheral blood [11].…”

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confidence: 99%

“…Recently, the anti-inflammatory effect of drug BAY 11-7082 was reported to be via suppression of the MyD88-dependent signaling network by targeting the ubiquitin system and not by inhibiting NF-κB [43]. Therefore, it may open a possibility that anti-inflammatory effect of 1,25(OH) 2 D 3 may be exerted through the suppression of MyD88-dependent signaling network.Women with RPL have various NK-cell dysfunction including increased NK-cell levels and cytotoxicities, upregulated CD107a and CD69 expression, and dysregulated cytokine production [10,12,22]. They also have downregulated killer inhibitory receptors and upregulated killer activating receptors on NK cells [13,22].…”

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confidence: 99%

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1,25‐Dihydroxy‐vitamin D3 regulates NK‐cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses

et al. 2015

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Vitamin D has a pivotal role in regulating immune responses by promoting Th2 immune responses and suppressing Th1 responses. Propensities to a Th1 immune response and increased NK-cell levels and cytotoxicity have been reported in women with recurrent pregnancy losses (RPL). In women with RPL, vitamin D deficiency is prevalent IntroductionVitamin D is a group of secosteroids and has a major role in maintaining skeletal health. Various effects of vitamin D on extra skeletal tissues have been reported as well, during the past decade [1]. Vitamin D deficiency is endemic for both men and women and across different age groups in the US population [2]. Low C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 3188-3199 Clinical immunology 3189vitamin D level has been linked to major common health problems in populations, particularly inflammatory conditions such as cardiovascular disease, cancers, diabetes, autoimmune diseases including multiple sclerosis, rheumatoid arthritis, and others [3]. In addition, vitamin D deficiency is a predisposing factor for various female diseases such as osteoporosis, uterine fibroids, endometriosis, and breast cancer and a risk factor for obstetrical complications such as gestational diabetes and preeclampsia [4,5]. Recently, we have reported that 47.4% of women with recurrent pregnancy losses (RPL) have vitamin D deficiency [6]. In women with RPL, decreased vitamin D level was associated with the increased prevalence of antiphospholipid antibody, antinuclear antigen antibody, anti-ssDNA, and anti-thyroperoxidase antibody. In addition, peripheral blood CD19 + B and CD56 + NK-cell levels and NK cytotoxicity were significantly higher in women with low vitamin D level when compared with those of normal vitamin D level [6]. Normal pregnancy is associated with Th2 shift in T-cell immunity [7]. The comparable shift in NK-cell immunity has been reported during normal pregnancy including a bias to NKr1 that produce IL-10 in peripheral blood, and NK3 cells that produce TGF-β in decidual NK cells [8]. Additionally, decidual innate lymphoid cell 3 (ILC3) may play a role in innate defenses, and vessel and tissue rebuilding, thus contributing to maintenance of pregnancy [9]. Contrarily, a propensity to Th1 immune response and increased NK-cell levels and cytotoxicity have been reported in women with RPL and multiple implantation failures (MIF) after in vitro fertilization and embryo transfer cycles [10]. Women with miscarriages and preeclampsia as well, have NK1 and NKT1 shift that produce high amounts of IFN-γ and little IL-4 in peripheral blood [11]. Therefore, cellular immune-regulation including innate immunity is critical for human reproduction.Women with RPL and MIF have significantly higher NK-cell levels and cytotoxicity, and dysregulated cytokine production patterns as compared to normal controls [10,12]. Activating receptor expression on NK cells was significantly increased, while inhibitory receptor expression was significantly decreased in ...

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Intravenous immunoglobulin G treatment increases live birth rate in women with recurrent miscarriage and modulates regulatory and exhausted regulatory T cells frequency and function

Jafarzadeh

Ahmadi

Dolati

et al. 2018

J of Cellular Biochemistry

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Exhausted T cells and regulatory T (Treg) cells have been recently proposed to be new risk factors for recurrent miscarriage (RM). Intravenous immunoglobulin G (IVIG) treatment reported to modulate various immune cells. In this study, the effects of IVIG on the frequency and function of exhausted T cells, exhausted Tregs, and Treg cells, as well as pregnancy outcome in women with unexplained RM (URM), were investigated. Ninety‐four pregnant women with RM were enrolled. At the time of positive pregnancy, blood samples were drawn. Forty‐four patients with URM were included as IVIG receiving treated group and received 400 mg/kg of IVIG and the rest fifty patients were considered as a control group and received no IVIG administration. IVIG was given intravenously every 4 weeks during 32 weeks of gestation. Blood samples of patients were collected after the latest administration. Exhausted T cells, exhausted Tregs, and Treg cells were evaluated pre‐ and posttreatment in both groups. IVIG induced a significant decrease in the frequency of exhausted Tregs population and function as well as a significant increase in Treg cells population, however, IVIG failed to affect population and the function of exhausted T cells. Pregnancy outcome was successful in IVIG treated women (86.3%) and were significantly different (P = 0.0006) in compared with the untreated URM subjects (42%). Therefore, employing of IVIG increases Treg cells and diminishes exhausted Tregs responses in RM patients with cellular immune anomalies throughout the pregnancy. Immunemodulatory effects of IVIG are probably associated with successful pregnancy outcome.

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Determination of Clinical Cellular Immune Markers in Women with Recurrent Pregnancy Loss

Abstract: Differences in NK cell percentages, NKC and Th1/Th2 cell ratio differentiated RPL from fertile controls.

Cited by 73 publications

References 56 publications

Competitive SWIFT cluster templates enhance detection of aging changes

Competitive SWIFT cluster templates enhance detection of aging changes

1,25‐Dihydroxy‐vitamin D3 regulates NK‐cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses

Intravenous immunoglobulin G treatment increases live birth rate in women with recurrent miscarriage and modulates regulatory and exhausted regulatory T cells frequency and function

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