Early Markers of Aggressive Periodontitis

描述(由申请人提供)：局限性侵袭性牙周炎(LAP)影响70,000名美国儿童，主要来自服务不足的社区。如果得不到治疗，可能会出现因牙齿脱落而造成的社会和心理耻辱。本研究旨在确定侵袭性牙周炎(EMAPS)的早期标志物。随着时间的推移，将检查包括伴生放线杆菌(AA)、其他微生物和宿主反应元素在内的风险标记物。将对青少年进行筛查，以选择250名AA阳性和250名AA阴性的牙周健康学生组成的平衡队列，这些学生将被登记并跟踪2年。本研究的目的是检测临床证据之前的骨丢失的微生物和宿主生物标志物，目的是开发一种椅子旁诊断系统来快速识别易感受试者。到目前为止，我们已经开发了一种测试，允许立即在椅子边识别患有再障的受试者，以及一种与BL相关的趋化因子测试。然而，我们的数据表明，仅有AA是不足以诊断的，巨噬细胞炎症蛋白1-α(MIP-1？)虽然是新的和与BL相关的，但可以通过寻找识别早期事件的标记来改进。将每3个月进行口腔上皮细胞(BECs)、唾液、菌斑和缝隙液的临床测量和采样。储存的样本将被前瞻性地分析，以评估在BL(AA和MIP-1？)之前的宿主和微生物生物标志物(唾液、裂隙和微生物元素)。并预测受试者(AIM 1a)和部位(AIM 1b)的骨丢失，然后当受试者(AIM 2a)和部位出现BL(AIM 2b)的放射学征象时，回顾地确定新的生物标志物早于BL。目的1a评价口腔黏膜上皮细胞上的AA与破骨细胞启动子唾液巨噬细胞炎性蛋白-1�联合应用是否可作为预测LAP的诊断指标。目的1b评估：1)建议的拮抗剂(包括AA、副血链球菌和金黄色葡萄球菌)和2)宿主反应元件(裂隙中的MIP-1�)作为预测6-9个月内牙齿部位BL的时间依赖性风险的标记物。目的2检查比AIM 1中检测的标记更早出现的宿主和微生物标志物。在检测BL后，3、6、9和12个月前采集的样本将在受试者水平上检测唾液和微生物因素，以促进该财团在BEC上的定植(AIM 2a)。在场地层面，我们将研究组成龈下LAP联合体的单个细菌的协调和时机，以确定以前未检测到的细菌(使用NextGen测序)是否也可能参与疾病的发生。此外，还将分析早期、中期和晚期宿主细胞因子在缝隙液中出现的顺序时间，以确定 生物标志物(AIM 2b)先于AIM 1中研究的标志物出现在BL部位。我们的前提是所获得的知识可以提供敏感和特异的生物标志物，可以取代目前在实践中使用的诊断工具。通过这种方式，可以在疾病的最早阶段识别出有风险的对象，从而可以制定具有成本效益的策略来 减少口腔健康差距。

DESCRIPTION (provided by applicant): Localized aggressive periodontitis (LAP) affects 70,000 US children, largely from underserved communities. If untreated social and psychological stigma resulting from tooth loss can occur. This study is designed to identify early markers of aggressive periodontitis (eMAPs). Risk markers that include Aggregatibacter actinomycetemcomitans (Aa), other microbes, and host response elements will be examined over time. Adolescents will be screened to select a balanced cohort of 250 Aa-positive and 250 Aa-negative periodontally healthy students who will be enrolled and followed for 2 years. The purpose of this study is to detect microbial and host biomarkers that precede clinical evidence of bone loss (BL) with the aim of developing a chair-side diagnostic system for rapid identification of susceptible subjects. Thus far, we have developed a test that permits immediate chair-side identification of subjects with Aa, and a test for chemokines related to BL. However, our data indicates that Aa alone is not sufficient for diagnosis, and macrophage inflammatory protein 1-alpha (MIP-1?) while novel and related to BL can be improved upon by finding markers that identify earlier events. Clinical measurements and sampling of buccal epithelial cells (BECs), saliva, plaque, and crevice fluid will be performed every 3 months. Stored samples will be analyzed prospectively to assess host and microbial biomarkers (salivary, crevicular and microbial elements) that predate BL (Aa and MIP-1?) and predict bone loss in a subject (AIM 1a) and at a site (AIM 1b), and then to retrospectively determine new biomarkers that predate BL when a subject (AIM 2a) and a site develops radiographic signs of BL (AIM 2b). AIM 1a assesses whether Aa on buccal cells in combination with salivary MIP-1�an osteoclast promoter, can serve as predictive diagnostic markers for individuals who will develop LAP. AIM 1b assesses levels of: 1) the proposed antagonists (a consortium of subgingival bacteria including Aa, S. parasanguinis and F. alocis), and 2) host response element (crevicular MIP-1� as predictive markers of time-dependent risk for BL at a tooth sites within 6-9 months. AIM 2 examines host and microbial markers that appear earlier than markers tested in AIM 1. After detection of BL, samples taken 3, 6, 9, and 12 months earlier will be tested for salivary and microbial factors that could promote colonization of the consortium on BECs at the subject level (AIM 2a). At the site level we will study the orchestration and timing of individual bacteria that make up the subgingival LAP consortium to determine if previously undetected bacteria (using NextGen sequencing) may also be involved in disease initiation. Further, sequential timing of early, middle, and late host cytokines as they appear in crevice fluid will be analyzed to identify biomarkers (AIM 2b) appearing at a BL site in advance of markers studied in AIM 1. Our premise is that the knowledge gained can provide sensitive and specific biomarkers that can supplant diagnostic tools used currently in practice. In this manner, subjects at risk can be identified in the earliest stages of disease so that cost-effective strategies can be instituted to reduce oral health disparities.