CD556, Infection, and Race in Preterm Delivery

描述(申请人提供)：以下地区的早产率 非裔美国人(AA)女性比高加索女性(CS)高1.5到2.4倍。 2010年国家公共卫生目标是消除#年的种族差距。 早产(PTD)。虽然PTD的发病机制尚不清楚，但感染 是牵涉到的主要民族因素之一。我们在这里提议统一一个 感染和宿主因素可能增加PTD风险的假说 在非裔美国人中(AA)。胎儿是半同种异体抗原 需要有效保护母体体液免疫系统。腐烂 加速因子(DAF)是一种保护性宿主因子，DAF表达在 母胎间期及其主要功能是保护细胞毒性 自体补体(C)攻击的影响。DAF表达由控制 孕酮(P)和孕酮(P)与妊娠丢失有关。感染 上调一氧化氮(NO)，进而NO下调DAF的表达。 DAF表达减少改变了母胎的保护质量 间期，并可能触发补体介导的炎症前期增加 肿瘤坏死因子(TNF)和前列腺素产生导致 PTL/PTD。我们认为，感染和生物/遗传因素都可能 导致内分泌-非免疫轴的紊乱。五花八门 多种因素共同作用可能改变母婴的C/DAF比率 从而导致前炎性/前列腺素活化 路径。感染或阴道感染时发生C级联反应和肿瘤坏死因子反应 殖民主义。强毒大肠埃希氏菌能够通过 大肠杆菌粘附素-宿主受体，并诱导侵袭性细胞因子反应。 尽管这些因素可能会影响所有女性，但由于 与生俱来的拒绝能力或高反应性 同种异体抗原。固有差异可能导致观察到的PTD AA和CS之间的差距。我们的建议如下：1.表征 DAF在择期妊娠AA和CS中的表达 足月儿、足月儿和假产儿。2.等位基因多态特征 DAF、TCB、Cr(a-)和TNFA等位基因及其可能的关联分析 感染、PTD和种族。3.阴道定植的基因分型 足月和早产患者的分离株。我们的长期目标是 项目是描述感染与PTL/PTD相关的机制，以及 宿主和致病因子在泌尿生殖系统间期相互作用的作用 在出生结局上。

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.