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：
Elena Martinelli
金额：
$ 8万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
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

来源：
https://reporter.nih.gov/project-details/10548583
关键词：
Address Africa South of the Sahara Angiogenic Factor Arteries Aspirin Authorization documentation Cells Cessation of life Clinical Cohort Studies Conceptions Control Groups Development Disease Dose Eclampsia Effectiveness Environment Etiology Exclusion Criteria Flow Cytometry Functional disorder Funding Gene Expression Profile Genetic Predisposition to Disease HIV HIV Infections Hemorrhage Hepatic Hypertension Immune Immune system Immunologics Immunosuppression Impairment Incidence Inflammatory International Maternal Pediatric Adolescent AIDS Clinical Trials Intervention Invaded Kidney Knowledge Lead Leadership Maternal Health Maternal Mortality Morbidity - disease rate Mothers Natural Killer Cells Organ Oxidative Stress P-Selectin PGF gene Perfusion Peripheral Blood Mononuclear Cell Phenotype Pilot Projects Placentation Play Pre-Eclampsia Predisposing Factor Pregnancy Pregnancy Complications Pregnant Women Prophylactic treatment Proteinuria Recommendation Reporting Residual state Resources Rest Risk Risk Factors Role Rupture Safety Sampling Sampling Studies Second Pregnancy Trimester Specific qualifier value Specimen Symptoms T-Lymphocyte Testing Third Pregnancy Trimester Time Vertical Disease Transmission Vulnerable Populations Woman antiretroviral therapy chemokine cohort cytokine design endothelial dysfunction exhaustion fetal high risk immune activation inflammatory marker maternal morbidity mortality pre-clinical transcriptome sequencing transcriptomics trophoblast

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.

项目概要/摘要先兆子痫（PE）是孕产妇和胎儿发病和死亡的主要原因。它是胎盘驱动的以胎盘发育和胎盘灌注改变为特征的疾病，导致临床症状胎盘氧化应激、高血压和蛋白尿阶段。 PE 的确切病因仍不清楚。然而，越来越多的证据表明，胎盘期间的免疫失衡可能会导致疾病的发展。特别是，PE 的特点似乎是在术后早期缺乏 Th1/Th2 转换。受孕以及免疫和血管生成环境改变，炎症标志物水平较高，耐受性标记物水平较低。此外，蜕膜 NK 细胞的表型和功能受损，这些细胞发挥着在胎盘形成中起关键作用，可能与干扰正确的滋养层侵袭有关。艾滋病毒感染未经治疗的孕妇似乎会降低早泄的发生率。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 HIV 感染女性可能会与未经治疗的女性或未感染的对照相比，患有 PE 的风险更高。 cART 对 PE 的发展仍不明朗。然而，区分受孕时 cART 和 cART 的研究已经开始据报道，在妊娠第二或第三个月期间接受 cART 治疗的受孕妇女中 PE 的发生率较高。在此处我们将检验以下假设：接受 cART 治疗的 HIV 感染孕妇的免疫失衡受孕有利于PE的发展。我们将调查收集的样本来检验我们的假设来自一项大型、已结束的 IMPAACT 研究 P1025。 P1025 研究样本将允许比较第二个以及在受孕时接受 cART 治疗的第 3 孕期早期妇女以及在第 2 个月开始接受 cART 的 HIV 感染妇女三个月。我们的两个具体目标集中在： SA1) 确定受孕时 cART 与已知的关联 PE 的血管生成和炎症标记物以及 SA2) 研究 T 细胞上是否存在免疫细胞标记物以及如何标记 NK 细胞亚群与血管生成标记物相关，已知这些标记物可以预测女性 PE 的发展受孕时接受 cART。总之，我们正在解决艾滋病毒感染者孕产妇健康的一个关键问题可以帮助确定和测试新策略的女性，以减少接受 cART 治疗的艾滋病毒中 PE 的发生感染的孕妇。