Assessment of angiogenesis modulators in pregnant women with pre-eclampsia: a case–control study

Mundim, Guilhermo Justino; Paschoini, Marina Carvalho; Júnior, Edward Araujo; Costa, Fabrício da Silva; Júnior, Virmondes Rodrigues

doi:10.1007/s00404-015-3823-x

Cited by 21 publications

(10 citation statements)

References 39 publications

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“…The role of IL‐6 in placental invasiveness during implantation has been described previously, but results regarding IL‐6 levels in preeclampsia patients are rather controversial . Recent studies have not observed differences in IL‐6 levels between preeclampsia and uncomplicated pregnancies, which is in agreement with our results.…”

Section: Discussionsupporting

confidence: 92%

Glutathione‐S‐transferase M1 polymorphism and pro‐inflammatory cytokines tumour necrosis factor‐α and interleukin‐1β are associated with preeclampsia in Serbian women

Jakovljević

Kontić-Vučinić

Nikolic

et al. 2019

American J Rep Immunol

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Problem Preeclampsia has a multifactorial origin with genetic, immunological, and environmental factors described as main contributors to its onset. This study aimed to investigate glutathione‐S‐transferase M1 (GSTM1) and glutathione‐S‐transferase T1 (GSTT1) gene polymorphisms, the expression of pro‐inflammatory cytokines (TNF‐α, IL‐1β, IL‐6), and the potential relationship between GST polymorphisms and cytokine expression levels in preeclampsia and uncomplicated pregnancy. Method of Study This prospective case‐control study included 50 women with preeclampsia and 50 healthy pregnant women. DNA and RNA were extracted from women leukocytes. Deletion polymorphisms were analyzed by PCR, while cytokine mRNA expression was analyzed by real‐time PCR. Results GSTM1 null genotype with present GSTT1 increased the risk for preeclampsia development. Deletion of GSTT1 without deletion of GSTM1 increased the risk for early preeclampsia. Relative mRNA expression of TNF‐α was significantly higher in preeclampsia compared to healthy pregnant women (P = 0.006). Expression of IL‐1β was significantly higher in severe and late preeclampsia compared to the control group (P = 0.005, P = 0.007, respectively). A significant positive correlation between TNF‐α and IL‐1β was observed (Spearman's ρ = 0.312, P = 0.028) and between IL‐1β and IL‐6, in preeclampsia group (Spearman's ρ = 0.296, P = 0.037). IL‐1β was significantly increased in patients with GSTT1 null genotype (P = 0.015) while IL‐6 was increased in patients with GSTM1 null genotype (P = 0.015). Conclusions GSTM1 null genotype represents a risk factor for preeclampsia development, while GSTT1 null genotype favors early preeclampsia. Preeclampsia is also associated with increased expression of pro‐inflammatory cytokines, predominantly TNF‐α and IL‐1β.

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Section: Discussionsupporting

confidence: 92%

Glutathione‐S‐transferase M1 polymorphism and pro‐inflammatory cytokines tumour necrosis factor‐α and interleukin‐1β are associated with preeclampsia in Serbian women

Jakovljević

Kontić-Vučinić

Nikolic

et al. 2019

American J Rep Immunol

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“…In our exploratory analysis, IL6 was associated with preeclampsia but only in white women. Overall, we found few associations between systemic immune markers and preeclampsia in second trimester samples which is consistent with other mid-trimester investigations [11, 12]. Thus, second trimester serum immune markers may have little use for prediction of preeclampsia.…”

Section: Discussionsupporting

confidence: 88%

“…A second trimester study has reported lower circulating IL10, TNF-α and IFN-γ among women who develop preeclampsia [10]. While others report no significant differences in circulating immune markers [11, 12]. First trimester investigations are limited.…”

Section: Introductionmentioning

confidence: 99%

First and second trimester immune biomarkers in preeclamptic and normotensive women

Taylor

Ness

Klebanoff

et al. 2016

Pregnancy Hypertension: An International Journal of Women's Car

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Introduction Circulating immune markers may be associated with preeclampsia but further investigations in early pregnancy and among preeclampsia subtypes are warranted. We examined immune markers in 208 preeclamptic women and 411 normotensive controls. Methods Our study was nested within the Collaborative Perinatal Project. A total of 242 women had first trimester serum samples and 392 had second trimester serum samples. Preeclampsia was defined as hypertension >20 weeks of gestation with proteinuria or pulmonary edema, oliguria, or convulsions. Preterm preeclampsia was defined as preeclampsia with delivery less than 37 weeks of gestation. Associations between immune markers RANTES, interleukin (IL)-6, IL4, IL5, IL12, IL10, IL8, IL1-beta, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and beta, transforming growth factor (TGF)-beta and preeclampsia were explored using a modified version of cox regression developed to address data with non-detectable levels. Models were adjusted for body mass index, gestational age of blood sampling, fetal sex, smoking, socioeconomic status and maternal age. Results In first trimester samples, IL-12 was associated with preeclampsia (p=0.0255). IFN-gamma (p=0.0063), IL1-beta (p=0.0006), IL5 (p=0.0422) and TNFr (p=0.0460) were associated with preterm preeclampsia only. In second trimester samples, IL1-beta was associated with preeclampsia (p=0.0180) and term preeclampsia (p=0.0454). After correction for multiple comparisons, only IL1-beta remained associated with preterm preeclampsia in the first trimester (p=0.0288). Discussion Elevated first trimester IL1-beta appears to be associated with preterm preeclampsia. However, few associations were observed in the second trimester. Systemic immune markers alone may not be useful for preeclampsia prediction.

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“…Nevertheless, two case‐control studies with 55 and 80 women. respectively, investigating serum levels in the third trimester, found no significant association of IL‐17 with the disease …”

Section: Resultsmentioning

confidence: 98%

The role of interleukins in preeclampsia: A comprehensive review

Bellos

Karageorgiou

Kapnias

et al. 2018

American J Rep Immunol

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Preeclampsia is a multi‐system hypertensive disorder of pregnancy, with significant rates of maternal and neonatal morbidity. It represents a major cause of preterm birth, as definitive treatment demands fetal delivery. Although its pathophysiology is complicated, placental hypoxia and endothelial dysfunction constitute established pathogenetic steps of the disease. Inflammation is considered to be a crucial mediator of preeclampsia process, as an imbalance between TH1, TH2, and TH17 immune responses is observed. The present review accumulates current knowledge about the contribution of interleukins in preeclampsia, summarizing the pathways through which each interleukin exerts its function in the disease. Also, the role of genetic polymorphisms is explored and the predictive efficacy of maternal serum interleukin levels is evaluated. Finally, recommendations about the safe interpretation of the outcomes, as well as guidance for future research, are provided.

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Assessment of angiogenesis modulators in pregnant women with pre-eclampsia: a case–control study

Abstract: Serum PlGF levels were reduced in the pregnant women with PE and were unrelated to disease severity. Serum levels of VEGF, IL-17, IL-10 and TNF-α were reduced in the pre-eclamptic pregnant women when compared with their normotensive peers, without statistically significant differences.

Cited by 21 publications

References 39 publications

Glutathione‐S‐transferase M1 polymorphism and pro‐inflammatory cytokines tumour necrosis factor‐α and interleukin‐1β are associated with preeclampsia in Serbian women

Glutathione‐S‐transferase M1 polymorphism and pro‐inflammatory cytokines tumour necrosis factor‐α and interleukin‐1β are associated with preeclampsia in Serbian women

First and second trimester immune biomarkers in preeclamptic and normotensive women

The role of interleukins in preeclampsia: A comprehensive review

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