Localized Aggressive Periodontitis: Microbial & Host Markers for Susceptibility

局部侵袭性牙周炎：微生物

• 批准号: 7468418
• 负责人: DANIEL H FINE
• 金额: $ 66.54万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ DENTAL SCHOOL
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7468418
• 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

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）：局部侵袭性牙周炎（Localized Aggregative Periodontitis，简称牙周炎）影响了大约70，000名美国儿童，主要来自服务不足的群体。如果不及时治疗，龋齿会导致第一磨牙和中切牙的缺失。该提案扩大了初步数据，并调查了表明细菌感染风险的微生物和宿主因素。这项研究将筛选3,000名来自纽瓦克的牙周健康儿童是否存在伴放线杆菌（Aa）。205例试验（Aa+）和410例对照（Aa-）将每隔6个月召回4-5年，以确定疾病发作的预测因素。筛查和回顾性检查包括牙周检查，收集唾液和颊细胞以及龈沟液和龈下菌斑从口袋网站和近中的所有第一磨牙。将储存样本以供将来分析。水平咬合翼片可用于确定牙颌畸形的诊断.当检测到骨质流失时，将分析储存的特定部位样本。修订后的提案包括两个目标：1.确定是否Aa、Aa的克隆或与Aa相关的植物群的200个成员可以预测Aa的发病; 2.研究宿主因素，可以影响Aa定植，持久性，龈下迁移和随后的激活先天性和获得性免疫因素与疾病发作。这些因素包括：乳铁蛋白的铁饱和度、针对Aa粘附素的伊加抗体滴度、一种抑制与Aa竞争的革兰氏+先锋菌斑微生物的生长调节因子（GMF）、针对白细胞毒素的IgG抗体水平和可影响疾病起始的21种细胞因子的水平。Aa+（试验组）和Aa-（对照组）数据的比较应提供信息，以确定微生物和宿主标志物的组合预测的风险，为发病。到目前为止，在那些被召回1年或更长时间的学生中，36名Aa+学生中有7名发生了自闭症，而Aa-学生中没有一名发生自闭症（p <0.01）。从被召回学生的唾液中获得的试验数据表明：1。来自Aa+学生的GMF可以在体外杀死先锋菌斑微生物（p <0.01），2. Aa反复定植的学生伊加水平较低; 3.一种特异性细胞因子MIP 1a在骨丢失前在Aa+/Ab受试者中显著升高（p <0.01）。从这项前瞻性研究中获得的知识应该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策略，以减少主要是非洲裔美国人和西班牙裔人口的口腔健康差异。