HIV immune environment impact on pre-eclampsia

项目摘要/摘要 子痫前期(PE)是导致母婴发病率和死亡率的主要原因。它是由胎盘驱动的 以胎盘发育和胎盘血流灌注改变为特征的疾病，导致临床 胎盘氧化应激期、高血压和蛋白尿。PE的确切病因尚不清楚。 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的特征似乎是早期缺乏Th1/Th2开关 受孕和免疫和血管生成环境的改变，炎性标志物和 较低水平的耐受标志物。此外，蜕膜NK细胞的表型和功能受损， 胎盘形成中的一个关键作用，可能涉及干扰正确的滋养细胞侵袭。中国的艾滋病毒感染情况 未经治疗的孕妇似乎导致了较低的PE发育率。这可能是由于艾滋病毒的驱动。 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会 与未经治疗的妇女或未感染的对照组相比，发生PE的风险更高。购物车对汽车的确切影响 PE的发展仍不明朗。然而，区分受孕车和购物车的研究开始了 在怀孕第二或第三个三个月期间，报告在怀孕时接受CART治疗的妇女发生PE的几率更高。在此 我们将检验这样一种假设，即接受CART治疗的HIV感染孕妇的免疫失衡 观念是体育发展的前提。我们将通过调查收集的样本来检验我们的假设 来自一项大型的IMPAACT研究结论，P1025。P1025研究样本将允许比较第二个 怀孕三个月的早期妇女在怀孕时使用购物车，而感染艾滋病毒的妇女在第二个月开始使用购物车 三个月。我们的两个具体目标集中在：SA1)确定受孕的CART与已知的联系 血管生成和炎症标志物PE和，SA2)研究T细胞上的免疫细胞标志物是否和如何 NK细胞亚群与血管生成标志物相关，已知这些标志物可预测女性PE的发展 怀孕时坐在购物车上。最后，我们正在解决感染艾滋病毒的产妇健康方面的一个关键问题。 可以帮助确定和测试减少CART治疗的艾滋病毒中PE发展的新策略的妇女 被感染的孕妇。

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.