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护理点(POC)诊断测试，以帮助临床医生识别易患牙周病进展的部位和/或对象。这个项目的主要目标是确定牙周病进展的生物标记物。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疾病的风险，并可能影响生育结果。此外，牙周病的进展经历了活动期的“爆发”和静止期。及早准确识别正在经历疾病进展的个人和/或部位对于发出信号表明需要立即干预以最大限度地减少牙齿丢失，允许适当分配资源来治疗易感人群，并限制这些感染的潜在全身后遗症。然而，目前还没有实用的临床手段来确定牙周部位和/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提高牙周病的诊断、指导治疗、监测活动性和评价治疗效果。目标1将检查GCF和唾液中宿主生物标记物水平的纵向变异性。目的研究牙周液和唾液中宿主生物标志物和唾液中未培养的和可培养的分类群在区分进行和非进展牙周部位和受试者中的诊断价值。目的3确定牙周治疗对唾液和GCF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类群的影响。支持这一建议的因素包括：1)两个NIH临床和翻译科学奖励中心(Forsyth研究所和密歇根口腔健康研究中心)的参与；2)两个中心在口腔液中宿主生物标记物的多重量化方面的丰富经验；3)使用新开发的RNA-寡核苷酸量化技术(ROQT)来量化未培养和可培养的细菌分类群；以及4)获得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“及早发现和识别牙周病风险因素”方面的战略兴趣，并重申了该中心“促进将科学转化为临床实践”的承诺。该项目的成功完成将导致验证可用于POC测试的生物标记物，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。 公共卫生相关性：尽管我们对与牙周炎相关的病因和危险因素的了解有所进步，但没有迹象表明牙周病患病率有所下降。事实上，牙齿保留的时间更长，加上人口老龄化，可能是未来因牙周破坏而受牙齿脱落影响的受试者数量增加的原因。治疗和预防牙周病的总支出估计以数十亿美元计。目前还没有实用的临床手段来确定哪些牙周部位或受试者是“活跃的”。牙周病进展的生物标志物的发现将为临床医生提供有关治疗需求、治疗结果评估和患者预后的重要信息，有助于改进预防和治疗策略。

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. PUBLIC HEALTH RELEVANCE: Despite advances in our knowledge of the causes and risk factors associated with periodontitis, there are no signs of a decline in periodontal disease prevalence. In fact, longer retention of teeth, coupled with an aging population might account for future increases in the number of subjects affected by tooth loss due to periodontal destruction. The total expenditure on treating and preventing periodontal diseases is estimated in billions of dollars. At present there are no practical clinical means of establishing which periodontal sites or subjects are "active". The discovery of biomarkers of periodontal disease progression would provide clinicians with important information regarding the need for treatment, evaluation of treatment outcomes and prognosis for patients that could help improve preventive and therapeutic strategies.