Race/Ethnicity/Immunity/Progesterone and Preterm Birth

种族/民族/免疫/黄体酮和早产

• 批准号: 6976904
• 负责人: CARL P WEINER
• 金额: $ 7.72万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6976904
• 关键词: African American; Hispanic Americans; biomarker; caucasian American; clinical research; cooperative study; defensins; enzyme linked immunosorbent assay; female; free radical oxygen; functional /structural genomics; genetic polymorphism; genetic susceptibility; human pregnant subject; immunogenetics; immunopharmacology; matrix assisted laser desorption ionization; pregnancy immunology; premature labor; progesterone; proteomics; racial /ethnic difference; surface enhanced laser desorption ionization; women' s health

DESCRIPTION: Preterm birth (PTB) remains a major public health problem, complicating >10% of all deliveries, and its associated perinatal morbidity and mortality represents 30% of the total. The greatest single risk factor for PTB is a prior PTB. Early and accurate identification of at risk patients may permit targeted interventions. Despite great effort, the US PTB rate has actually increased over the past 30y. This failure reflects a poor understanding of the basic mechanisms initiating PTB coupled to a long held assumption that preterm labor (PL) is simply term labor ill timed. Ascending infection from the lower genital is a well-recognized as a mechanism of upper tract inflammation, fetal inflammatory response syndrome, decidual hemorrhage, chorioamnionitis or combinations thereof. Yet, antibiotic therapy has failed to reduce the PTB rate. It is likely other therapeutic strategies are necessary once the innate immunity of the lower genital tract is overwhelmed and the inflammatory cascade established in the upper genital tract or fetal compartment. We hypothesize that PTB reflects an alteration of oxygen independent (defensins and calgranulins) and oxygen dependent (oxygen free radicals) defense mechanisms of the lower and upper genital tract, and that the sequestration of certain polymorphisms in genes regulating the inflammatory cascade among some ethnic groups accounts in part for their risk of recurrent PTB (Specific Aim 1a). We hypothesize women destined for PTB express cervicovaginal biomarkers illustrative of altered innate immunity weeks or months before onset of PTB symptoms (cervical ripening, preterm labor contractions or pPROM) that can be reliably identified using proteomic tools (Specific Aim 1b). We hypothesize that the progesterone compounds reported to decrease recurrent PTB affect maternal lower and upper genital tract defense mechanisms as well as the fetal inflammatory response axis (Specific Aim 2). This proposal brings together an experienced multidisciplinary team who will test elements of these hypotheses in experiments performed over a 5y period.

描述：早产（PTB）仍然是一个重大的公共卫生问题，占所有分娩的10％，其相关的围产期发病率和死亡率占总数的30％。 PTB最大的单一风险因素是先前的PTB。对AT风险患者的早期和准确识别可能允许有针对性的干预措施。尽管付出了巨大的努力，但在过去30年中，美国PTB的利率实际上已经上升了。这种失败反映了对启动PTB的基本机制的不良理解，该机制与长期以来的假设相结合，即早产劳动（PL）只是术语不适的时间。从下生殖器的上升感染是一种被广泛认可的，是上层炎症，胎儿炎症反应综合征，骨出血，绒毛膜膜炎或组合的机制。然而，抗生素疗法未能降低PTB率。一旦下生殖道的先天免疫力不堪重负，并且在生殖器上层或胎儿室中建立的炎症级联反应可能是其他治疗策略。我们假设PTB反映了氧独立的（防御素和加仑蛋白）和氧气依赖性（氧气自由基）的上等生殖道的防御机制，并且在某些种族群体中，在某些民族群体中，在某些种族级联的基因中，某些基因中的某些多态性的序列是对其在某些种族中的特殊性ct pertect pertains pert of teper te Prent of the teper of the tem teper tist ct的风险。我们假设妇女注定要在PTB表达宫颈阴道生物标志物，说明了可以使用蛋白质组学工具（特定的目标1B）可靠地识别出可以可靠地识别的PTB症状（颈能成熟，早产劳动收缩或PPROM）数周或几个月前的先天免疫力。我们假设据报道降低复发性PTB的孕激素化合物会影响母体下部生殖道防御机制以及胎儿炎症反应轴（特定目标2）。该提案汇集了一个经验丰富的多学科团队，他们将在5年期间进行实验中测试这些假设的要素。