Biomarkers of Periodontal Disease Progression

描述（由申请人提供）：我们研究的长期目标是开发一种即时（POC）诊断测试，以帮助临床医生识别易受牙周病进展影响的部位和/或受试者。该项目的主要目的是确定牙周病进展的生物标志物。中心假设是宿主分析物和龈下物种的组合将有效地作为牙周病进展的生物标志物。 牙周病是美国成年人牙齿脱落的最常见原因，最近的研究表明，它们增加了心血管疾病，糖尿病，呼吸系统疾病等全身性疾病的风险，并可能影响生殖结果。此外，牙周病的进展是通过“爆发”的活动，然后是静止期。早期准确识别正在经历活动性疾病进展的个体和/或部位对于发出需要立即干预的信号至关重要，以最大限度地减少牙齿脱落，允许适当分配资源以治疗易感个体，并限制这些感染的潜在全身后遗症。然而，没有实际的临床手段来识别牙周部位和/或正在进展的受试者。迫切需要更好的牙周病活动性生物标志物来改善牙周病诊断，指导治疗，监测活动性和评估治疗反应。 目的1将检查GCF和唾液中宿主生物标志物水平的纵向变异性。目的2将检查GCF和唾液中宿主生物标志物水平以及唾液和龈下生物膜样品中未培养和可培养的分类群的诊断效用，以区分进展和非进展的牙周部位和受试者。目的3将确定牙周治疗对唾液和龈沟液生物标志物水平的影响，以及对唾液和龈下生物膜中未培养和可培养的分类群的影响。 加强这一建议的因素包括：1）两个NIH临床和转化科学奖中心的参与（福赛斯研究所和密歇根口腔健康研究中心）; 2）两个中心在口腔液中宿主生物标志物的多重定量方面的丰富经验; 3）获得新开发的RNA-寡核苷酸定量技术（ROQT），用于定量未培养和可培养的细菌分类群;以及4）访问最先进的生物信息学核心以支持大型数据集的分析。 该项目解决了NIDCR在“早期发现和识别牙周病风险因素”方面的战略利益，并重申了该中心“促进科学转化为临床实践”的承诺。该项目的成功完成将导致可用于POC检测的生物标志物的验证，以帮助临床医生识别需要立即干预的疾病进展风险部位和受试者。

DESCRIPTION (provided by applicant): The long term goal of our research is to develop a point-of-care (POC) diagnostic test to help clinicians identify sites and/or subjects that are susceptible to periodontal disease progression. The primary objective of this project is to identify biomarkers of periodontal disease progression. The central hypothesis is that a combination of host analytes and subgingival species will be effective as biomarkers of periodontal disease progression. Periodontal diseases are the most common cause of tooth loss among adults in the United States and recent studies suggested that they increase the risk for systemic conditions such as cardiovascular diseases, diabetes, respiratory diseases and can affect reproductive outcome. Further, periodontal diseases progress through "bursts" of activity followed by periods of quiescence. Early accurate identification of individuals and/or sites that are undergoing active disease progression is critical to signal the need for immediate intervention to minimize tooth loss, allow for proper allocation of resources to treat susceptible individuals, and limit the potential systemic sequelae of these infections. However, there are no practical clinical means of identifying periodontal sites and/or subjects that are progressing. Better biomarkers of periodontal disease activity are urgently needed to improve periodontal disease diagnosis, guide therapy, monitor activity, and evaluate treatment response. Aim 1 will examine the longitudinal variability of levels of host biomarkers in GCF and saliva. Aim 2 will examine the diagnostic utility of GCF and salivary levels of host biomarkers and uncultivated and cultivable taxa in saliva and in subgingival biofilm samples for discriminating progressing and non-progressing periodontal sites and subjects. Aim 3 will determine the effects of periodontal therapy on the levels of salivary and GCF biomarkers and on uncultivated and cultivable taxa in saliva and in subgingival biofilms. Factors that strengthen this proposal include: 1) participation by two NIH Clinical and Translational Science Award centers (The Forsyth Institute and Michigan Center for Oral Health Research); 2) vast experience of both Centers in multiplex quantification of host biomarkers in oral fluids; 3) access to the newly developed RNA-oligonucleotide quantification technique (ROQT) for quantifying uncultivated and cultivable bacterial taxa; and 4) access to state-of-the-art bioinformatics cores to support analysis of large data sets. This project addresses the NIDCR's strategic interest in "early detection and identification of risk factors for periodontal disease" and reaffirms the center's commitment to "facilitate the translation of science into clinical practice". Successful completion of this project will lead to validation of biomarkers that can be used in POC tests to help clinicians identify sites and subjects at risk for disease progression who require immediate intervention.