HIV immune environment impact on pre-eclampsia

HIV免疫环境对先兆子痫的影响

基本信息

  • 批准号:
    10548583
  • 负责人:
  • 金额:
    $ 8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-06-01 至 2024-05-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Pre-eclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality. It is a placental-driven disease characterized by alterations in placental development and placental perfusion that lead to the clinical stage of placental oxidative stress, hypertension and proteinuria. The exact etiology of PE is still unknown. However, a growing body of evidence suggests that immune imbalances during placentation may drive the development of the disease. In particular, PE seems to be characterized by a lack of Th1/Th2 switch early after conception and an altered immune and angiogenic environment with higher levels of inflammatory markers and lower levels of tolerogenic markers. Moreover, impaired phenotype and function of decidual NK cells, which play a critical role in placentation, are probably involved interfering with correct trophoblast invasion. HIV infection in untreated pregnant women appears to drive lower rates of PE development. This may be due to HIV-driven immune suppression. However, HIV infected women treated with combination antiretroviral therapy (cART) may be at higher risk of PE than untreated women or uninfected controls. The exact impact of cART on the development of PE is still unclear. However, studies that distinguish cART at conception from cART started during the 2nd or 3rd trimester report higher incidence of PE in women treated with cART at conception. Herein we will test the hypothesis that immune imbalances in HIV infected pregnant women treated with cART at conception predispose to the development of PE. We will test our hypothesis investigating samples collected from a large, concluded IMPAACT study, P1025. The P1025 study samples will allow for the comparison of 2nd and early 3rd trimester women on cART at conception with HIV infected women who started cART during the 2nd trimester. Our two specific aims focus on: SA1) determining the association of cART at conception with known angiogenic and inflammatory markers of PE and, SA2) investigating if and how immune cell markers on T cell and NK cell subsets correlate with angiogenic markers that are known to predict the development of PE in women on cART at conception. In conclusion, we are addressing a critical problem in maternal health in HIV infected women that could help to identify and test new strategies to reduce the development of PE in cART-treated HIV infected pregnant women.
项目总结/摘要 先兆子痫(PE)是导致母亲和胎儿发病和死亡的主要原因。这是一个胎盘驱动的 以胎盘发育和胎盘灌注改变为特征的疾病,导致临床 胎盘氧化应激阶段、高血压和蛋白尿。PE的确切病因仍然未知。 然而,越来越多的证据表明,胎盘形成过程中的免疫失衡可能会导致 疾病的发展。特别是,PE的特征似乎是缺乏Th 1/Th 2转换后早期 概念和改变免疫和血管生成环境与更高水平的炎症标志物, 较低水平的致耐受性标志物。此外,蜕膜NK细胞的表型和功能受损, 在胎盘形成中起关键作用,可能涉及干扰正确的滋养层侵入。HIV感染 未经治疗的孕妇似乎会降低PE的发生率。这可能是由于艾滋病毒驱动的 免疫抑制然而,接受联合抗逆转录病毒疗法(cART)治疗的艾滋病毒感染妇女可能 患肺栓塞的风险高于未经治疗的妇女或未感染的对照组。cART的确切影响 PE的发展仍不明朗。然而,从概念上区分cART和cART的研究开始于 在妊娠第二或第三个三个月期间,报告妊娠时接受cART治疗的女性PE发生率较高。本文 我们将检验接受cART治疗的HIV感染孕妇免疫失衡的假设, 体育观念的发展对体育教育的发展具有决定性的作用。我们将测试我们的假设调查样本收集 来自一项大型、已结束的IMPAACT研究,P1025。P1025研究样品将允许比较第2个 妊娠早期接受cART治疗的妊娠晚期妇女与妊娠第2周开始cART治疗的HIV感染妇女 三个月我们的两个具体目标集中在:SA 1)确定cART在概念上与已知的 PE和SA的血管生成和炎症标志物2)研究T细胞上的免疫细胞标志物是否以及如何 NK细胞亚群与血管生成标志物相关,这些标志物已知可预测女性PE的发生 在怀孕时服用cART。最后,我们正在处理艾滋病毒感染者孕产妇保健方面的一个关键问题, 妇女,可以帮助确定和测试新的战略,以减少发展的PE在cART治疗的艾滋病毒 感染的孕妇。

项目成果

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Elena Martinelli其他文献

Elena Martinelli的其他文献

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{{ truncateString('Elena Martinelli', 18)}}的其他基金

Turning off HIV White Noise: Switching from Long-Lived to Short-Lived Reservoir
关闭艾滋病毒白噪声:从长寿命库切换到短寿命库
  • 批准号:
    10676478
  • 财政年份:
    2023
  • 资助金额:
    $ 8万
  • 项目类别:
Exploration into the Forgotten HIV Reservoir with Models of HIV/SIV Persistence in Mucosal Tissues
利用粘膜组织中 HIV/SIV 持续存在的模型探索被遗忘的 HIV 病毒库
  • 批准号:
    10460078
  • 财政年份:
    2022
  • 资助金额:
    $ 8万
  • 项目类别:
HIV immune environment impact on pre-eclampsia
HIV免疫环境对先兆子痫的影响
  • 批准号:
    10629367
  • 财政年份:
    2022
  • 资助金额:
    $ 8万
  • 项目类别:
TGFBR1 Blockade as Novel Release and Kill HIV Strategy
TGFBR1 阻断作为新的释放和杀死 HIV 策略
  • 批准号:
    10358122
  • 财政年份:
    2021
  • 资助金额:
    $ 8万
  • 项目类别:
Role of integrins in HIV/SIV transmission across cervico-vaginal mucosa
整合素在 HIV/SIV 宫颈阴道粘膜传播中的作用
  • 批准号:
    8440738
  • 财政年份:
    2012
  • 资助金额:
    $ 8万
  • 项目类别:
Role of integrins in HIV/SIV transmission across cervico-vaginal mucosa
整合素在 HIV/SIV 宫颈阴道粘膜传播中的作用
  • 批准号:
    8263136
  • 财政年份:
    2012
  • 资助金额:
    $ 8万
  • 项目类别:
Role of integrins in HIV/SIV transmission across cervico-vaginal mucosa
整合素在 HIV/SIV 宫颈阴道粘膜传播中的作用
  • 批准号:
    8610236
  • 财政年份:
    2012
  • 资助金额:
    $ 8万
  • 项目类别:

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