CD556, Infection, and Race in Preterm Delivery

CD556、感染和早产中的种族

• 批准号: 6786742
• 负责人: Bogdan J Nowicki
• 金额: $ 29.8万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-24 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6786742
• 关键词: African American; CD antigens; Escherichia coli; alleles; bacteria infection mechanism; caucasian American; clinical research; complement pathway; decay accelerating factor; female; gene expression; genetic polymorphism; genotype; gestational age; histopathology; human subject; inflammation; polymerase chain reaction; pregnancy loss; premature infant human; premature labor; racial /ethnic difference; restriction fragment length polymorphism; tissue /cell culture; tumor necrosis factor alpha; virulence

DESCRIPTION (provided by applicant): The rate of preterm delivery among African American (AA) women is 1.5 to 2.4 times higher than Caucasian (CS). The 2010 national public health goal is eliminating ethnic disparity in preterm delivery (PTD). Although the mechanism of PTD is unclear, infections are among the main ethnologic factors implicated. We propose here a unifying hypothesis by which infection and host factors may increase the risk of PTD among African Americans (AA). The fetus is a semiallogenic antigen that requires efficient protection from the maternal humoral immune system. Decay accelerating factor (DAF) is a protective host factor DAF is expressed in the feto-maternal interphase and its main function is protection from cytotoxic effect of autologous complement (c)attack. DAF expression is controlled by progesterone (P) and P was implicated in pregnancy losses. Infection upregulates nitric oxide (NO) and in turn NO downregulates DAF expression. Decreased DAF expression alters the protective quality of the feto-maternal interphase and may trigger complement mediated increases in proinflarnmatory tumor necrosis factor (TNF), and prostaglandin production resulting in PTL/PTD. We propose that both infection and biologic/genetic factors may contribute to the disturbances in the endocrine-NO-immune axis. Various factors in concert may act to alter the C/DAF ratio in the feto-maternal interface thereby leading to the activation of proinflammatory/prostaglandin pathway. The C cascade and TNF response occurs upon infection or vaginal colonization. Virulent E. coli is capable to display synergistic signaling via E.coli adhesin-host receptor and elicit aggressive cytokine responses. Although these factors may effect all women, AA are at higher risk due to an increased inherent capacity of rejection or hyperresponsiveness of alloantigens. The inherent differences may result in the observed PTD disparities between AA and CS. We propose to the following: 1. Characterize expression of DAF among AA and CS women undergoing elective pregnancy tennination, term and pretenn labor. 2. Characterize allelic polymorphism in the DAF Tcb, Cr(a-), and TNFA alleles and analyze possible association with infection, PTD and race. 3. Characterize genotypes of vaginal colonization isolates in patients with term and preterm delivery. The long-term goal of our project is to characterize mechanism of infection associated PTL/PTD and the role of the host and pathogen factors interacting at the urogenital interphase in birth outcome.

描述（由申请人提供）： 早产率 非裔美国 (AA) 女性的发病率是白人 (CS) 女性的 1.5 至 2.4 倍。 2010年国家公共卫生目标是消除种族差异 早产（PTD）。尽管 PTD 的机制尚不清楚，但感染 是所涉及的主要民族学因素之一。我们在这里提出一个统一的 感染和宿主因素可能增加 PTD 风险的假设 非裔美国人 (AA) 中。胎儿是一种半同种异体抗原 需要来自母体体液免疫系统的有效保护。衰变 加速因子（DAF）是一种保护性宿主因子，DAF 的表达形式为 胎儿-母体间期，其主要功能是防止细胞毒性 自体补体 (c) 攻击的影响。 DAF 表达由以下因素控制 黄体酮 (P) 和 P 与妊娠失败有关。感染 上调一氧化氮 (NO)，进而 NO 下调 DAF 表达。 DAF 表达减少会改变母胎的保护质量 间期并可能触发补体介导的促炎细胞增加 肿瘤坏死因子（TNF）和前列腺素的产生导致 PTL/PTD。我们认为感染和生物/遗传因素都可能 导致内分泌-NO-免疫轴紊乱。各种各样的 因素的协同作用可能会改变胎儿-母体的 C/DAF 比率 界面从而导致促炎/前列腺素的激活 途径。 C 级联反应和 TNF 反应发生在感染或阴道感染时 殖民化。强毒大肠杆菌能够通过以下方式显示协同信号： 大肠杆菌粘附素宿主受体并引发侵袭性细胞因子反应。 尽管这些因素可能会影响所有女性，但 AA 的风险更高，因为 增加固有的排斥能力或高反应性 同种异体抗原。固有的差异可能会导致观察到的 PTD AA和CS之间的差异。我们提出以下建议： 1. 表征 选择性妊娠 AA 和 CS 妇女中 DAF 的表达 终止、期限和假劳动。 2. 表征等位基因多态性 DAF Tcb、Cr(a-) 和 TNFA 等位基因并分析与 感染、PTD 和种族。 3. 表征阴道定植的基因型 足月和早产患者中的分离株。我们的长期目标 该项目的目的是表征与 PTL/PTD 相关的感染机制以及 宿主和病原体因子在泌尿生殖间期相互作用的作用 在出生结果中。