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（由申请人提供）：局部侵袭性牙周炎（LAP）影响了70,000名美国儿童，其中大部分来自服务不足的社区。如果不及时治疗，可能会出现因牙齿脱落而导致的社会和心理耻辱。本研究旨在确定侵袭性牙周炎（eMAPs）的早期标志物。风险标记包括放线菌聚集菌（Aa）、其他微生物和宿主反应因素将随着时间的推移进行检查。将对青少年进行筛选，以选择250名牙周健康的aa阳性和250名aa阴性学生，这些学生将被登记并随访2年。本研究的目的是检测骨质流失（BL）临床证据之前的微生物和宿主生物标志物，目的是开发一种椅子侧诊断系统，用于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，可以立即识别Aa患者，以及一种与BL相关的趋化因子测试。然而，我们的数据表明，单独的Aa不足以诊断，巨噬细胞炎症蛋白1- α (MIP-1?)，虽然是新的，但与BL相关，可以通过寻找识别早期事件的标记来改善。每3个月进行一次口腔上皮细胞（BECs）、唾液、牙菌斑和牙缝液的临床测量和取样。存储的样品将进行前瞻性分析，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、缝隙和微生物元素），并预测受试者（AIM 1a）和部位（AIM 1b）的骨质流失，然后当受试者（AIM 2a）和部位出现BL的放射学征像（AIM 2b）时，回顾性地确定在BL之前的新生物标志物。AIM 1a评估口腔细胞上的Aa与唾液MIP-1（一种破骨细胞启动子）是否可以作为LAP患者的预测性诊断标志物。AIM 1b评估以下水平：1)拟议的拮抗剂（牙龈下细菌的联盟，包括Aa，副anguinis和F. alocis），以及2)宿主反应元件（沟MIP-1）作为6-9个月内牙齿部位BL时间依赖性风险的预测标志物。AIM 2检查宿主和微生物标记，比AIM 1中检测的标记出现得早。在检测到BL后，将在受试者水平上对3、6、9和12个月前采集的样本进行唾液和微生物因素的检测，这些因素可能促进该联盟在BECs上的定植（AIM 2a）。在位点水平，我们将研究组成牙龈下LAP联盟的单个细菌的编排和时间，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，早期、中期和晚期宿主细胞因子出现在缝隙液中的顺序时间将被分析以确定