Novel approaches for mechanistic understanding and predicting preeclampsia

Department of Pediatrics, Women and Infants Hospital-Warren Alpert Medical School of Brown University, Providence, RI, USA.
Journal of Reproductive Immunology (Impact Factor: 2.82). 10/2009; 83(1-2):134-8. DOI: 10.1016/j.jri.2009.08.006
Source: PubMed


Despite intense investigation, preeclampsia (PE) remains largely enigmatic. Relatively late onset of diagnostic signs and heterogeneous nature of the disease further contribute to poor understanding of its etiology and clinical management. There exist no concrete animal models that can provide mechanistic underpinnings for evaluating targeted therapeutic intervention. Poor cross-sectional findings with potential biochemical markers reported so far have proved counterintuitive and suggest a need for novel approaches to predict the early onset of disease. Because of the co-onset of local placental anomalies and systemic manifestation of symptoms, it is highly likely that serum from PE patients can provide a "blueprint" of causative factors. Proteomic and/or functional analysis of maternal serum are expected to predict the onset of disease ahead of manifestation of clinical symptoms. A serum-based predictive assay should overcome complexities resulting from the heterogeneous etiology of PE. This review attempts to address some of these issues and discuss the signature biochemical serum factors and propose new and better ways to predict PE.

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    • "In this study, we demonstrated that vitamin D induced VEGF and G-CSF production in peripheral NK cells. Lower expression of VEGF has been reported in women with pre-eclampsia or intrauterine growth restriction (Dunk and Ahmed, 2001;Kalkunte et al., 2009).Molvarec et al. (2010)reported that the percentage of VEGF-producing peripheral blood NK cells was significantly lower in women with pre-eclampsia compared with that of healthy pregnant women. Consequently, dysregulation of VEGF production by NK cells at the feto–maternal interface may cause poor angiogenesis and pregnancy complications such as RPL or preeclampsia . "
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    ABSTRACT: STUDY QUESTION Do women with recurrent pregnancy losses (RPL) and low vitamin D have increased prevalence of auto- and cellular immune abnormalities when compared with women with RPL who have normal vitamin D, and does vitamin D have any effect on cellular immunity in vitro? SUMMARY ANSWER A high proportion of women with RPL have vitamin D deficiency and the risk of auto- and cellular immune abnormalities is increased in women with RPL and vitamin D deficiency. WHAT IS KNOWN ALREADY Vitamin D deficiency in pregnant women is associated with increased risk of obstetrical complications such as pre-eclampsia, bacterial vaginosis associated preterm delivery, gestational diabetes mellitus and small-for-gestational age births. STUDY DESIGN, SIZE, DURATION A retrospective cross-sectional study of 133 women with RPL who were enrolled in a 2-year period, together with laboratory experiments. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with three or more consecutive spontaneous abortions prior to 20 weeks of gestation who were enrolled at the University clinic. Serum vitamin D level, cellular activity and autoimmune parameters in vivo and in vitro were measured. MAIN RESULTS AND THE ROLE OF CHANCE Sixty-three out of 133 women (47.4%) had low vitamin D (
    Full-text · Article · Nov 2013 · Human Reproduction
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    • "and adaptive immune system that may have an influence on the onset of this disorder. It was suggested that activation of cell-mediated immunity might play a key role in the aetiology of pre-eclampsia (Darmochwal-Kolarz et al., 2007; Kalkunte et al., 2009; Saito and Sakai, 2003; Santner- Nanan et al., 2009; Sasaki et al., 2007). Dendritic cells (DCs) are antigen-presenting cells with the unique ability to induce primary immune responses. "
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    ABSTRACT: The aim of our study was to estimate the expression of B7-H1 and B7-H4 molecules on myeloid and plasmacytoid dendritic cells (DCs) in the peripheral blood of patients with pre-eclampsia, normal pregnant women and healthy non-pregnant women. Thirty-three patients with pre-eclampsia, 26 normal pregnant women, and 12 healthy non-pregnant women were included in the study. Dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies against blood dendritic cell antigens and B7-H1 and B7-H4 molecules and estimated using flow cytometry. The expression of B7-H1 and B7-H4 molecules was significantly higher on CD1c(+) myeloid and CD303(+) plasmacytoid DCs in the first trimester of pregnancy than in the luteal phase of the ovarian cycle (CD1c(+)B7-H1(+): 19.19±10.55% vs. 11.99±6.79%; p<0.05; CD1c(+)B7-H4(+): 12.01±9.15% vs. 3.98±1.97%, p<0.001; CD303(+)B7-H1(+): 4.15±2.38% vs. 1.70±0.87%, p<0.05; CD303(+)B7-H4(+): 5.44±2.93% vs. 2.33±1.54%, p<0.01). Moreover, the expression of the B7-H1 molecule on CD1c(+) DCs in the second trimester of normal pregnancy was significantly higher than in the first trimester, but in the third trimester they decreased compared with the second trimester (II vs. I trimester: 32.23±11.30% vs. 19.19±10.55%, p<0.01; III vs. II trimester: 32.23±11.30% vs. 22.39±8.19%, p<0.01). The expression of B7-H1 molecule on CD1c(+) myeloid and CD303(+) plasmacytoid DCs was significantly lower in pre-eclampsia than in healthy third-trimester pregnant women (CD1c(+)B7-H1(+): 13.78±6.26% vs. 22.39±8.19%, p<0.05; CD303(+)B7-H1(+): 3.66±2.46% vs. 8.65±3.15%, p<0.01). Higher expressions of B7-H1 and B7-H4 molecules on CD1c(+) myeloid and CD303(+) plasmacytoid DCs in the first trimester of pregnancy suggest the role they play in the immunomodulation during early pregnancy.
    Full-text · Article · Jun 2013 · Journal of Reproductive Immunology
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    • "PE is a systemic disorder resulting from poor placentation. Although the pathogenesis of PE remains poorly understood, improper trophoblast invasion and poor spiral artery remodeling resulting in placental ischemia/hypoxia are the major pre-clinical events at the maternal-fetal interface (Brosens, et al., 1977; Meekins et al., 1994; Redman and Sargent 2009; Kalkunte, et al., 2009b). As a consequence, placenta-derived flux of inflammatory molecules and anti-angiogenic factors are observed in maternal systemic circulation resulting in endothelial dysfunction and symptoms of hypertension, proteinuria and kidney pathology (Levine, et al., 2004, Parikh and Karumanchi, 2008). "
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    ABSTRACT: IL-10 is a pregnancy compatible cytokine that plays a vital role in maintaining the balance of anti-inflammatory and pro-inflammatory milieu at the maternal-fetal interface. Recent evidence now suggests that IL-10 is a potent vascular cytokine that can blunt hypertension and inflammation-mediated vascular dysfunction. Thus, a re-evaluation of IL-10 as a cytokine supporting endovascular interactions and angiogenesis as well as blunting hypoxic-injury and preeclampsia-like features is warranted. In this review, we highlight these novel functions of IL-10 and propose that its immune-modulating and vascular functions are mutually inclusive, particularly in the context of normal gestation.
    Preview · Article · Feb 2011 · Journal of Reproductive Immunology
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