Localized Aggressive Periodontitis: Microbial & Host Markers for Susceptibility

局部侵袭性牙周炎：微生物

• 批准号: 7871397
• 负责人: DANIEL H FINE
• 金额: $ 68.57万
• 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/7871397
• 关键词: Actinobacillus; Actinobacillus actinomycetemcomitans; Affect; African American; Age; 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; Methods; Microarray Analysis; Microbe; Modeling; Movement; 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 (LAP) 影响大约 70,000 名美国儿童，其中大部分来自服务不足的群体。如果不治疗，LAP 可能会导致第一磨牙和中切牙脱落。该提案扩展了初步数据并调查了指示 LAP 风险的微生物和宿主因素。这项研究将对来自纽瓦克的 3,000 名牙周健康儿童进行筛查，以确定是否存在伴放线杆菌 (Aa)。 205 测试 (Aa+) 和 410 对照 (Aa-) 将在 4-5 年内每隔 6 个月进行一次回顾，以确定预测疾病发作的因素。筛查和回忆检查包括牙周检查、收集唾液和颊细胞以及来自袋状部位和所有第一磨牙近中的裂隙液和龈下菌斑。样品将被存储以供将来分析。水平咬翼射线照片用于建立 LAP 诊断。当检测到骨质流失时，将对存储的特定部位样本进行分析。修订后的提案包括 2 个目标： 1. 确定 Aa、Aa 的克隆或与 Aa 相关的菌群的 200 个成员是否可以预测 LAP 的发生； 2. 检查可影响 Aa 定植、持久性、龈下迁移以及随后与疾病发作相关的先天和获得性免疫因子激活的宿主因素。这些因素包括：乳铁蛋白的铁饱和度、针对 Aa 粘附素的 IgA 抗体滴度、杀死与 Aa 竞争的革兰氏+先驱菌斑微生物的生长修饰因子 (GMF)、针对白细胞毒素的 IgG 抗体水平以及可影响疾病发生的 21 种细​​胞因子的水平。 Aa+（测试）和 Aa-（对照）组的数据比较应提供信息，以确定预测 LAP 发病风险的微生物和宿主标志物的组合。迄今为止，在那些回忆了 1 年或以上的学生中，36 名 Aa+ 学生中有 7 名患有 LAP，而 Aa- 对照学生中没有一个患有 LAP (p <.01)。从召回的学生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 < .01)，2. 在反复被 Aa 定植的学生中发现 IgA 水平较低，3. 在骨质流失之前，Aa+/LAP 受试者中一种特定的细胞因子 MIP 1a 显着升高 (p <.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记，该测试可用于设计预防策略，以减少以非裔美国人和西班牙裔为主的人口的口腔健康差异。