CD556, Infection, and Race in Preterm Delivery

描述（由申请人提供）： 非裔美国人（AA）女性比高加索人（CS）高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）。虽然PTD的机制尚不清楚，但感染 是主要的民族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风险的假说 非裔美国人（AA）胎儿是一种半同种异体抗原， 需要有效的保护免受母体体液免疫系统的侵害。衰减 加速因子（Accelerating Factor，简写为ERF）是一种保护性宿主因子， 母胎间期，其主要功能是保护免受细胞毒性 自体补体（C）攻击作用。控制表达式的是 孕酮（P）和P与妊娠丢失有关。感染 上调一氧化氮（NO），而NO反过来下调TNF α表达。 降低的表达改变了胎儿-母体的保护质量 可能触发补体介导的促炎性因子增加 肿瘤坏死因子（TNF）和前列腺素的产生， PTL/PTD。我们认为，感染和生物/遗传因素可能 有助于内分泌-NO-免疫轴的紊乱。各种 协同因素可能会改变胎儿-母体中的C/C比值， 界面，从而导致促炎/前列腺素的激活 通路C级联反应和TNF反应发生在感染或阴道感染后。 殖民化毒力E.大肠杆菌能够显示协同信号转导， 大肠杆菌粘附素-宿主受体，并引发攻击性细胞因子反应。 虽然这些因素可能会影响所有妇女，AA是在较高的风险，由于 固有的排斥或高反应能力增加， 同种抗原固有差异可能导致观察到的PTD AA和CS之间的差异。我们建议如下：1.表征 择期妊娠AA和CS妇女中BMP 1的表达 终止、期限和假劳动。2.表征等位基因多态性， 和TNFA等位基因，并分析可能与 感染PTD和种族3.表征阴道定植的基因型 足月分娩和早产患者中的分离株。我们的长期目标是 该项目旨在表征感染相关PTL/PTD的机制， 宿主和病原体因子在泌尿生殖间期相互作用的作用 出生结果。

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.