Early Markers of Aggressive Periodontitis

侵袭性牙周炎的早期标志物

• 批准号: 9214235
• 负责人: DANIEL H FINE
• 金额: $ 63.4万
• 依托单位: RBHS-SCHOOL OF DENTAL MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-15 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9214235
• 关键词: Actinobacillus actinomycetemcomitans; Adolescent; Affect; Agglutination; Appearance; Bacteria; Biological Markers; Cells; Child; Clinical; Communities; Data; Data Analyses; Deltastab; Detection; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic radiologic examination; Diagnostic tests; Disease; Early identification; Elements; Enrollment; Epithelial Cells; Evaluation; Event; Future; Goals; Grant; Health; Immune response; Individual; Institutes; Intervention; Knowledge; Liquid substance; Longitudinal Studies; Macrophage Inflammatory Protein-1; Measurement; Methods; Microbe; Modeling; Mouth Diseases; National Institute of Dental and Craniofacial Research; Onset of illness; Oral; Oral Diagnosis; Oral health; Osteoclasts; Periodontal Diseases; Periodontitis; Population; Preventive Intervention; Protocols documentation; Public Health; Research Design; Response Elements; Risk; Risk Marker; Roentgen Rays; Saliva; Salivary; Salivary immunoglobulin A; Sampling; Schools; Side; Site; Small Inducible Cytokine A3; Specificity; Streptococcus; Students; Surveys; Symbiosis; System; Systemic disease; Testing; Time; Tissues; Tooth Loss; Tooth structure; Translating; Visit; Vulnerable Populations; antimicrobial; base; bone loss; chemokine; clinical application; cohort; commensal microbes; cost effective; cytokine; design; diagnostic biomarker; health disparity; high risk; improved; killings; member; microbial; microbial host; next generation sequencing; novel; predictive marker; promoter; prospective; psychologic; public health relevance; saliva diagnostic; screening; social; social stigma; specific biomarkers; tool; tooth surface

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.

描述（由适用提供）：局部侵略性牙周炎（LAP）影响了70,000名美国儿童，主要来自服务不足的社区。如果可能因牙齿脱落而导致的未经治疗的社会和心理污名。这项研究旨在确定侵袭性牙周炎（EMAP）的早期标志。随着时间的流逝，将检查包括聚集的放线菌（AA），其他微生物和宿主反应元素的风险标记。青少年将被筛选，以选择250个AA阳性和250个AA阴性的牙周健康学生的平衡队列，他们将被招募并遵循2年。这项研究的目的是检测骨质流失临床证据（BL）之前的微生物和宿主生物标志物，目的是开发椅子侧诊断系统，以快速鉴定易感受试者。那远，我们已经开发了一项测试，该测试允许立即对具有AA的受试者进行椅子侧识别，并对与BL相关的趋化因子进行了测试。但是，我们的数据表明，单独的AA不足以诊断，而巨噬细胞炎症蛋白1-α（MIP-1？），而新颖且与BL相关的新颖和与BL相关，可以通过找到识别早期事件的标记来改善。每3个月将每3个月进行颊上皮细胞（BEC），唾液，斑块和缝隙液的临床测量和取样。将对储存的样品进行前瞻性分析，以评估预测BL（AA和MIP-1？）的宿主和微生物生物标志物（唾液，刺激和微生物元素），并预测受试者（AIM 1A）和位点（AIM 1B）的骨骼流失（AIM 1B）（AIM 1B），然后追溯确定a受试者的新生物标志物（AIM 2A）和AIM（目标2A），并启用了AIM（AIM 2A），并启用了（AIM 2A）。 AIM 1A评估是否可以与唾液MIP-1``AA''AA与破骨细胞启动子结合使用，可以作为将会发展膝盖的个体的预测诊断标记。目标1B评估水平：1）拟议的拮抗剂（包括AA，S。arasanguinis和F. alocis在内的缩减细菌的财团）和2）宿主响应元件（缝隙MIP-1。 6、9和12个月，将测试可以在受试者水平上促进BEC的唾液和微生物因子（AIM 2A）。将分析在缝隙液中出现的细胞因子以识别 生物标志物（AIM 2B）出现在AIM 1中的标志物研究之前出现在BL站点上。我们的前提是，所获得的知识可以提供敏感且特定的生物标志物，可以取代当前实际上使用的诊断工具。以这种方式，可以在疾病的最早阶段确定处于危险的受试者，以便可以将具有成本效益的策略制定为 减少口腔健康差异。