Elevated serum soluble fms-like tyrosine kinase 1 (sFlt1) level in women with hydatidiform mole

Koga, Kaori; Osuga, Yutaka; Tajima, T.; Hirota, Yasushi; Igarashi, Toshio; Fujii, Tomoyuki; Yano, Tetsu; Taketani, Yuji

doi:10.1016/j.fertnstert.2009.02.015

Cited by 55 publications

(36 citation statements)

References 14 publications

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“…44 hCG is being secreted immediately after pregnancy establishment, whereas its levels diminish toward the third trimester. 25 However, high levels of hCG in PE patients have been described in contrast to NP, 26 which we could confirm in this study. We also showed that placenta explants from PE patients released higher amounts of hCG than placenta explants from NP women.…”

Section: Cd5supporting

confidence: 83%

“…25 We discarded that the classical B-cell survival factor BAFF, known to be elevated in autoimmune diseases, 26 could be responsible for the augmentation in the frequency of CD19 ϩ CD5 ϩ cells in PE, because no differences in BAFF levels could be observed between NP women and PE patients ( Figure S3). We, therefore, turned our attention to soluble factors released by the placenta.…”

Section: Cd5mentioning

confidence: 99%

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CD19 ⁺ CD5 ⁺ Cells as Indicators of Preeclampsia

et al. 2012

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Abstract-Preeclampsia is a devastating pregnancy-associated disorder affecting 5% to 8% of pregnant women worldwide.It emerges as an autoimmune-driven disease, and, among others, the autoantibodies against angiotensin type 1 receptor II have been proposed to account for preeclampsia symptoms. Despite much attention focused on describing autoantibodies associated with preeclampsia, there is no clue concerning the cell population producing them. CD19 ϩ CD5 ϩ B-1a B cells constitute the main source of natural and polyreactive antibodies, which can be directed against own structures. Here, we aimed to identify the B-cell subpopulation responsible for autoantibody production during preeclampsia and to study their regulation, as well as their possible use as markers for the disease. The frequency of CD19 ϩ CD5 ϩ cells in peripheral blood of preeclamptic patients is dramatically increased compared with normal pregnant women as analyzed by flow cytometry. This seems to be driven by the high human chorionic gonadotropin levels present in the serum and placenta supernatant of preeclamptic patients versus normal pregnant women. Not only Ϸ95% of CD19 ϩ CD5 ϩ cells express the human chorionic gonadotropin receptor, but these cells also expand on human chorionic gonadotropin stimulation in a lymphocyte culture. Most importantly, isolated CD19 ϩ CD5 ϩ cells produce autoantibodies against angiotensin type 1 receptor II, and CD19 ϩ CD5 ϩ cells were further detected in the placenta of preeclamptic but not of normal pregnancies where barely B cells are present. Our results identify a B-cell population able to produce pregnancy-pathological autoantibodies as possible markers for preeclampsia, which opens vast diagnostic and therapeutic applications. P reeclampsia (PE) is a devastating human pregnancyassociated disorder characterized by the onset of hypertension, proteinuria, and edema after the 20th week of pregnancy. It represents one of the most frequent medical complications of pregnancy, affecting Ϸ5% to 8% of all pregnant women. 1 Limited progress has been achieved in identifying the causes, being the induction of delivery the only available treatment for the clinical symptoms. 2 Recently, the idea that PE may represent an autoimmune disease has emerged. 3 This is based on the fact that many autoantibodies were identified in PE patients and suspected to account for the symptoms of the disease. [4][5][6] Much attention was focused on autoantibodies against angiotensin type 1 receptor II (AT 1 -AAs), because they have been detected in the serum of PE patients. 7 These autoantibodies are able to bind to and to activate the AT 1 angiotensin receptor, leading to the release of antiangiogenic factors from the placenta, which are reportedly involved in the origin of the disease. [8][9][10] In spite of the efforts put on identifying autoantibodies related to PE, no attention has been so far focused on the cell population responsible for their production. This is a very important piece of information, because it may provide a novel tar...

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Section: Cd5supporting

confidence: 83%

Section: Cd5mentioning

confidence: 99%

CD19 ⁺ CD5 ⁺ Cells as Indicators of Preeclampsia

et al. 2012

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“…Circulating levels of sFlt-1 begin to rise before the onset of clinical symptoms (Levine et al 2004) and correlate with the severity of the disease (Chaiworapongsa et al 2004), suggesting important diagnostic and predictive potential (Cerdeira and Karumanchi 2010). Several risk factors for preeclampsia can also be correlated with increased sFlt-1 such as multigestational pregnancies (Bdolah et al 2008;Maynard et al 2008), hydatidiform mole (Koga et al 2010), trisomy 13 , and nulliparity . Potential additional contributors as a source of sFlt-1 besides trophoblasts include peripheral blood mononuclear cells ) and proteolytic shedding of extracellular fragment of Flt-1 in endothelial cells (Rahimi et al 2009;Zhao et al 2010), but the clinical significance of these sources is unknown.…”

Section: Preeclampsiamentioning

confidence: 99%

Angiogenic Factors in Preeclampsia and Related Disorders

Cerdeira

Karumanchi

2012

Cold Spring Harbor Perspectives in Medicine

101

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“…Preeclampsia [63][64][65][66][67]69,70,72,[92][93][94][95][96][97][98][99][100][101][102][103], as well as other obstetrical syndromes [46,[104][105][106][107][108][109][110][111][112][113][114][115][116][117][118], is characterized by an anti-angiogenic state. Plasma concentrations of the angiogenic factor, placental growth factor (PlGF), are decreased [69,70,92,93,96,[100][101][102], and the anti-angiogenic factors (soluble vascular endothelial growth factor receptor-1 [sVEGFR-1] and soluble endoglin [sEng]) are elevated both prior to [67,72,[119]…”

Section: Introductionmentioning

confidence: 99%

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Stampalija

Chaiworapongsa

Romero

et al. 2013

The Journal of Maternal-Fetal & Neonatal Medicine

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Objectives: Angiogenic/anti-angiogenic factors have emerged as one of the promising biomarkers for the prediction of preeclampsia. Since not all patients with preeclampsia can be identified by these analytes, the search for additional biomarkers continues. The soluble form of ST2 (sST2), a protein capable of binding to interleukin (IL)-33 and thus contributing to a Th1-biased immune response, has been reported to be elevated in maternal plasma of women with preeclampsia. The aims of this study were to examine: (1) differences in maternal plasma concentrations of sST2 and IL-33 between women diagnosed with preeclampsia and those having uncomplicated pregnancies; (2) the relationship between sST2, umbilical and uterine artery Doppler velocimetry, and the severity of preeclampsia; and (3) the performance of sST2 and angiogenic/anti-angiogenic factors in identifying patients with preeclampsia at the time of diagnosis. Methods: This cross-sectional study included women with preeclampsia (n ¼ 106) and women with an uncomplicated pregnancy (n ¼ 131). Plasma concentrations of sST2, IL-33, soluble vascular endothelial growth factor receptor (sVEGFR)-1, soluble endoglin (sEng) and placental growth factor (PlGF) were determined by enzyme linked immune sorbent assay. Area under the receiver operating characteristic curve (AUC) for the identification of preeclampsia was examined for each analyte. Results: (1) Patients with preeclampsia had a higher mean plasma concentrations of sST2 than those with an uncomplicated pregnancy (p50.0001), while no significant difference in the mean plasma concentration of IL-33 between the two groups was observed; (2) the magnitude of this difference was greater in early-onset, compared to late-onset disease, and in severe compared to mild preeclampsia; (3) sST2 plasma concentrations did not correlate with the results of uterine or umbilical artery Doppler velocimetry (p ¼ 0.7 and p ¼ 1, respectively) among women with preeclampsia; (4) sST2 correlated positively with plasma concentrations of sVEGFR1-1 and sEng (Spearman's Rho ¼ 0.72 and 0.63; each p50.0001), and negatively with PlGF (Spearman's Rho ¼ À0.56, p50.0001); and (5) while the AUC achieved by sST2 and angiogenic/anti-angiogenic factors in identifying women with preeclampsia at the time of diagnosis were non-significantly different prior to term (537 weeks of gestation), thereafter the AUC achieved by sST2 was significantly less than that achieved by angiogenic/anti-angiogenic factors. Conclusions: Preeclampsia is associated with increased maternal plasma concentrations of sST2. The findings that sST2 concentrations do not correlate with uterine or umbilical artery Doppler velocimetry in women with preeclampsia suggest that elevated maternal plasma sST2 concentrations in preeclampsia are not related to the increased impedance to flow in the uteroplacental circulation. The performance of sST2 in identifying preeclampsia at the time of diagnosis prior to 37 weeks of gestation was comparable to that of angiogenic/anti-angiogenic f...

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Elevated serum soluble fms-like tyrosine kinase 1 (sFlt1) level in women with hydatidiform mole

Cited by 55 publications

References 14 publications

CD19 ⁺ CD5 ⁺ Cells as Indicators of Preeclampsia

CD19 ⁺ CD5 ⁺ Cells as Indicators of Preeclampsia

Angiogenic Factors in Preeclampsia and Related Disorders

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

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Elevated serum soluble fms-like tyrosine kinase 1 (sFlt1) level in women with hydatidiform mole

Cited by 55 publications

References 14 publications

CD19 + CD5 + Cells as Indicators of Preeclampsia

CD19 + CD5 + Cells as Indicators of Preeclampsia

Angiogenic Factors in Preeclampsia and Related Disorders

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

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Product

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CD19 ⁺ CD5 ⁺ Cells as Indicators of Preeclampsia

CD19 ⁺ CD5 ⁺ Cells as Indicators of Preeclampsia