Localized Aggressive Periodontitis: Microbial & Host Markers for Susceptibility

局部侵袭性牙周炎：微生物

基本信息

批准号：
7321527
负责人：
DANIEL H FINE
金额：
$ 69.66万
依托单位：
UNIV OF MED/DENT OF NJ-NJ DENTAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-15 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7321527
关键词：
Actinobacillus Actinobacillus actinomycetemcomitans Affect African American Age All Sites Antibodies Bacteria Bacterial Adhesins Bacterial Antigens Bite Cells Child Collection Contralateral Control Groups Data Diagnosis Diagnostic tests Disease Environment Epithelial Cells Evaluation Exhibits Future Gingival Crevicular Fluid Growth Growth Factor Hispanics Immune Immunoglobulin A Immunoglobulin G In Vitro Incidence Incisor Inflammatory Integration Host Factors Iron Knowledge Lactoferrin Lead Liquid substance Localized Methods Microarray Analysis Microbe Modeling Movement Numbers Onset of illness Oral Oral cavity Oral health Organism Periodontitis Predictive Factor Predisposition Prevalence Prevention strategy Prospective Studies Race Research Personnel Reverse Transcriptase Polymerase Chain Reaction Risk Saliva Salivary Salivary immunoglobulin A Sampling Screening procedure Site Small Inducible Cytokine A3 Students Surface Surveys Testing Time Tooth structure Wing base bone loss cytokine design health disparity human disease killings leukotoxin member microbial microbial host microorganism migration response sample collection sex tooth surface

Actinobacillus Actinobacillus actinomycetemcomitans Affect African American Age All Sites Antibodies Bacteria Bacterial Adhesins Bacterial Antigens Bite Cells Child Collection Contralateral Control Groups Data Diagnosis Diagnostic tests Disease Environment Epithelial Cells Evaluation Exhibits Future Gingival Crevicular Fluid Growth Growth Factor Hispanics Immune Immunoglobulin A Immunoglobulin G In Vitro Incidence Incisor Inflammatory Integration Host Factors Iron Knowledge Lactoferrin Lead Liquid substance Localized Methods Microarray Analysis Microbe Modeling Movement Numbers Onset of illness Oral Oral cavity Oral health Organism Periodontitis Predictive Factor Predisposition Prevalence Prevention strategy Prospective Studies Race Research Personnel Reverse Transcriptase Polymerase Chain Reaction Risk Saliva Salivary Salivary immunoglobulin A Sampling Screening procedure Site Small Inducible Cytokine A3 Students Surface Surveys Testing Time Tooth structure Wing base bone loss cytokine design health disparity human disease killings leukotoxin member microbial microbial host microorganism migration response sample collection sex tooth surface

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项目摘要

DESCRIPTION (provided by applicant): Localized Aggressive Periodontitis (LAP) affects approximately 70,000 U.S. children, largely from underserved groups. If untreated, LAP can lead to loss of first molars and central incisors. The proposal expands on preliminary data and surveys microbial and host factors indicative of LAP risk. This study will screen 3,000 periodontally healthy children from Newark for the presence of Actinobacillus actiinomycetemcomitans (Aa). 205 test (Aa+) and 410 control (Aa-) will be recalled at 6-month intervals for 4-5 yrs to identify factors predictive of disease onset. Screening and recall exams include a periodontal examination, collection of saliva and buccal cells as well as crevicular fluid and subgingival plaque from pocketed sites and the mesial of all 1st molars. Samples will be stored for future analysis. Horizontal bite- wing radiographs are used to establish the LAP diagnosis. When bone loss is detected, stored site-specific samples will be analyzed. The revised proposal includes 2 aims: 1. to determine whether Aa, clones of Aa, or 200 members of the flora associated with Aa could be predictive of the onset of LAP; 2. to examine host factors that can affect Aa colonization, persistence, subgingival migration and subsequent activation of innate and acquired immune factors associated with disease onset. These factors include: iron-saturation of lactoferrin, IgA antibody titers to Aa adhesins, a Growth Modifying Factor (GMF) that killls Gram+ pioneer plaque microbes that compete with Aa, IgG antibody levels to leukotoxin and levels of 21 cytokines that can affect disease initiation. Comparison of data from Aa+ (test) and Aa- (control) groups should provide information with which to determine the combination of microbial and host markers predictive of risk for LAP onset. To date in those recalled for 1yr or more, 7 of 36 Aa+ students have developed LAP, while none of the Aa- conrols have LAP (p <.01). Pilot data from saliva obtained from students recalled indicates the following; 1. GMF from Aa+ students can kill pioneer plaque microbes in vitro (p < .01), 2. lower IgA levels are found in students repeatedly colonized by Aa, and 3. a specific cytokine, MIP 1a, is significantly elevated in Aa+/LAP subjects prior to bone loss (p <.01). The knowledge gained from this prospective study should identify markers required to develop a salivary-based diagnostic test that can be used to design preventive strategies to reduce oral health disparities in this predominantly African American and Hispanic population.

描述（由申请人提供）：局部侵略性牙周炎（LAP）影响约70,000名美国儿童，主要来自服务不足的群体。如果未经治疗，膝盖会导致第一磨牙和中央门牙的损失。该提案扩展了初步数据，并调查微生物和宿主因素，指示膝盖风险。这项研究将筛查纽瓦克的3,000名牙周健康的儿童，以侵蚀肌动杆菌（AA）。 205测试（AA+）和410对照（AA-）将以6个月的间隔召回4 - 5年，以识别预测疾病发作的因素。筛查和召回检查包括牙周检查，唾液和颊细胞的收集，以及缝隙的液体和从袖珍部位的尺寸以及所有第一磨牙的中牙的尺寸。样品将存储以供将来分析。水平咬合射线照片用于建立膝盖诊断。当检测到骨质流失时，将分析存储的位点特异性样品。修订后的提案包括2个目标：1。确定AA，AA的克隆或与AA相关的200名成员是否可以预测圈速的发作； 2。检查可能影响AA定殖，持久性，替代迁移以及随后激活与疾病发作相关的先天和获得的免疫因素的宿主因素。这些因素包括：乳铁蛋白的铁饱和，IgA抗体对AA粘附素的滴度，AA粘附蛋白的生长修饰因子（GMF），可杀死与AA，IgG抗体水平与白细胞毒素和21种细胞因子水平的IgG抗体水平竞争的，可影响疾病起步。对AA+（测试）和AA-（对照）组的数据的比较应提供信息，以确定微生物和宿主标记的组合，可预测膝盖发作风险。迄今为止，在召回1年或以上的人中，有36位AA+学生中有7个已经出现了圈速，而AA-Conrols都没有圈速（p <.01）。从召回的学生那里获得的唾液的试点数据表明以下内容； 1。来自AA+学生的GMF可以在体外杀死先锋斑块微生物（p <.01），2。在通过AA反复殖民的学生中发现IgA水平较低，而3。特定的细胞因子MIP 1A，MIP 1A，MIP 1A，在AA+/LAP受试者中的AA+/LAP受试者中显着升高（p <.01）。从这项前瞻性研究中获得的知识应确定开发基于唾液的诊断测试所需的标志物，该测试可用于设计预防性策略，以减少这一主要是非洲裔美国人和西班牙裔人口中的口腔健康差异。