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

Abstract

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...

New lenses to look at preeclampsia

“…These findings are in agreement with epidemiological studies [11] and with predictive studies as we will see in the next paragraph [15][16][17][18][19]. Indeed, the multi-facets clinical manifestations of HDP [9,10] could fit well into two different pathophysiological models and, consequently, two completely different patterns of placental damage and clinical phenotypes: on one hand, the placenta with incomplete spiral artery remodeling resulting in HDP associated with IUGR (HDP-IUGR), and on the other hand, the placenta with deregulated perfusion due to an over-expansion of terminal villi [20,21] resulting in HDP associated with fetuses with appropriate for gestational age growth (HDP-AGAf).…”

“…These findings on the role of BMI underline, on one side, the role of maternal predisposing conditions for metabolic syndrome, low-grade inflammation, the endothelial dysfunction that might be associated to late placental damage and hypertension not associated with IUGR. On the other side, shallow trophoblastic placentation, reflected by abnormal uterine arteries Doppler velocimetry, is at the basis of the trophoblastic oxidative stress and disbalance of angiogenic and anti-angiogenic factors [15,16]. The latter, ultimately, might damage maternal endothelium at the basis of systemic hypertension and/or cause other function or organ damage.…”

Towards biomarker-based tests that can facilitate decisions about prevention and management of preeclampsia in low-resource settings

“…Among the 36 experimental biomarkers listed in Table 1, the following biomarkers have been shown to have some degree of clinical sensitivity and specificity to PE when compared to BP and/or proteinuria and could be of interest for future PE screening tests: 1) eight blood biomarkers consisting of CA-125 [32], C-terminal GRP78 [35], HSD17B1 [39], NGAL [55], plasma factor VII [50], serum uric acid (UA) [53], sFlt1-14 [56], and soluble ST2 [54] 2) five urine markers consisting of KIM-1 [43], NGAL [43], podocyturia [48], inositol [40], and MDA [44]. Another 10 blood experimental biomarkers (AT-1AA [31], calcyclin, copeptin [34], galectin-1 [36], Gas6 [37], HIF-1aOH [38], IGFALS [41], mammalian HtrA3 [45], NT-proBNP [47], and PTX3 [49]), and four urine ones (C5b-9 [33], nephrin [46], iodine [42], and prolactin [52]) had limited clinical evaluation information, which impeded the evaluation of their performance for the diagnosis of PE.…”

L’implantation embryonnaire

“…À l'inverse, chez d'autres patientes ayant un historique de fausses couches à répétition, une activation et une cytotoxicité excessives des cellules uNK, ainsi qu'une augmentation d'IL18 aux conséquences abortives, ont été identifiées [54]. D'autre part, une perturbation de l'équilibre du système IL33 est positivement corrélée à l'interruption de la grossesse et à un risque de prééclampsie [55,56]. Enfin, les études récentes de l'expression endométriale de l'IL33 et de son récepteur ont montré que LIF PTGS2 SDF1 RANTES IL8 VEGFC MCP IL6 MMP9 MMP3 MMP13 TIMP3 VCAM1 ITGB8 IL1RN IL1R1 IL1R3 IL1 IL18R1 IL18 ST2 l'interruption de l'équilibre sST2/IL33 lors de la décidualisation de l'endomètre prédispose au risque de fausse couche [57,58].…”