Mechanisms and Treatment Response of Aggressive Periodontitis in Children

儿童侵袭性牙周炎的发病机制和治疗效果

• 批准号: 8269133
• 负责人: Luciana Macchion Shaddox
• 金额: $ 42.84万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8269133
• 关键词: Affect; African American; Age; Age of Onset; Bacteria; Bacterial Antigens; Bacterial Infections; Case Study; Child; Clinical; Clinical Research; Clinical Trials; Complex; Controlled Study; Data; Defect; Detection; Diagnosis; Diagnostic; Disease; Disease Progression; Environment; Enzymes; Etiology; Figs - dietary; Florida; Future; Gingival Crevicular Fluid; Goals; Health; Hyperactive behavior; Immune response; Immune system; Incisor; Individual; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Intervention; Knowledge; Low Prevalence; Matrix Metalloproteinases; Mediator of activation protein; Metalloproteases; Microarray Analysis; Microbial Biofilms; Mouth Diseases; Outcome Study; Pathogenesis; Patients; Pattern; Periodontal Diseases; Periodontitis; Population; Process; Research; Ribosomal RNA; Role; Severities; Site; Technology; Testing; Therapeutic Intervention; Tissues; Tooth Loss; Underserved Population; base; bone; chemokine; cohort; conventional therapy; cytokine; disease characteristic; improved; microbial; oral infection; premature; prevent; public health relevance; subgingival biofilm; tool; trait; treatment response

DESCRIPTION (provided by applicant): Aggressive periodontitis (AgP) is a group of rare, but severe, rapidly progressing form of periodontitis, characterized by an early age of onset and rapid bone destruction that leads to early tooth loss. It appears that this disease result from a combination of bacterial infection and hyperactivity of the immune system. However, given its rare occurrence and difficulties in gathering large populations, knowledge on specific mechanisms and consequently proper treatment of this disease remains based on case reports and a few small clinical trials. We have identified a cohort of at least fifty African-American children diagnosed within one clinical setting in Tallahassee, Florida, with a very similar pattern of localized AgP (LAgP). This group represents a small underserved population of north Florida. Our preliminary data shows an exacerbated immune response and specific groups of bacteria involved with this disease. With proper diagnostic tools and with the knowledge we have already gained within this population, we believe we are able to gather a larger population to further understand this aggressive disease and the effects conventional treatment has upon its mechanisms. Therefore, the overall goal of this study is to determine which mechanisms are responsible for the rapid tissue destruction in children with aggressive periodontitis, and how conventional periodontal intervention affects these mechanisms. Our central hypothesis is that AgP is associated with a combination of a hyper- inflammatory innate trait and a specific group of bacteria and that periodontal therapy is able to modulate these parameters responsible for tissue destruction. In order to test our hypothesis we propose to: 1- To determine if 'traditional' periodontal treatment alters the hyper-responsive trait observed in LAgP by evaluating the systemic regulatory mechanisms of cyto/chemokine expression which contribute to tissue destruction; 2- To determine how local inflammatory mediators and metalloproteinases are modulated through the progression and treatment of periodontal disease in children with LAgP.; and 3- To determine alterations in subgingival microflora associated with LAgP after traditional periodontal treatment. We hope that the outcomes of this study will provide us with a better understanding of the mechanisms involved with aggressive periodontal tissue destruction in children and how treatment affects these mechanisms. This will enables us to investigate early and improved treatment approaches to prevent early tooth loss and possible future systemic complications. PUBLIC HEALTH RELEVANCE: Although of low prevalence, aggressive periodontitis is a rapid destructive form of periodontal disease that initiates at a young age, leading to premature loss of first molars and incisors. Little is known on the mechanisms of this disease. It is imperative to understand mechanisms of disease to establish proper treatment. We have established a controlled study in a homogeneous population presenting similar aggressive disease characteristics to evaluate the mechanisms of this disease longitudinally. It is the goal of this study to determine immunological and microbiological mechanisms responsible for the rapid tissue destruction in children with localized aggressive periodontitis and how conventional periodontal intervention affects these mechanisms. Important knowledge gained with this proposal will aid in defining specific treatment approaches to better control disease progression and prevent disease initiation in susceptible individuals.

描述（由申请人提供）：侵略性牙周炎（AGP）是一组罕见但严重，迅速发展的牙周炎形式，其特征是发病和快速骨骼破坏，导致早期牙齿脱落。看来这种疾病是由于细菌感染和免疫系统多动性的结合而引起的。但是，鉴于其很少发生和收集大量人群的困难，有关特定机制的知识以及因此对该疾病的适当治疗仍然基于病例报告和一些小型临床试验。我们已经确定了在佛罗里达州塔拉哈西（Tallahassee）的一个临床环境中诊断出的至少五十名非洲裔美国儿童的队列，其局部AGP模式非常相似。该群体代表了北佛罗里达州的一小部分人口。我们的初步数据显示，与该疾病有关的细菌和特定细菌组的恶化。有了适当的诊断工具，并且借助我们已经在该人群中获得的知识，我们相信我们能够收集更大的人群，以进一步了解这种侵略性疾病，并影响常规治疗对其机制的影响。因此，这项研究的总体目标是确定哪些机制造成了侵袭性牙周炎儿童的快速组织破坏，以及常规牙周干预如何影响这些机制。我们的中心假设是，AGP与过度炎性先天性和特定细菌的组合有关，该牙周治疗能够调节这些造成组织破坏的这些参数。为了检验我们的假设，我们建议：1-确定“传统”牙周治疗是否通过评估Cyto/趋化因子表达的全身调节机制来改变LAGP中观察到的超响应性特征，从而有助于组织破坏组织； 2-确定局部炎症性介质和金属蛋白酶如何通过延伸和治疗LAGP儿童的牙周疾病进行调节。 3-确定传统牙周处理后与LAGP相关的尺寸菌群的改变。我们希望这项研究的结果将使我们对儿童侵袭性牙周组织破坏涉及的机制有更好的了解，以及治疗如何影响这些机制。这将使我们能够调查早期和改进的治疗方法，以防止早期牙齿脱落和未来可能的系统并发症。 公共卫生相关性：尽管患病率较低，但侵略性牙周炎是一种牙周疾病的快速破坏性形式，在年轻时引发，导致过早失去第一磨牙和门牙。关于这种疾病的机制知之甚少。必须了解建立适当治疗的疾病机制。我们已经在同质人群中建立了一项对照研究，该研究具有相似的攻击性疾病特征，以纵向评估该疾病的机制。这项研究的目的是确定负责局部侵袭性牙周炎儿童快速组织破坏以及常规牙周干预如何影响这些机制的免疫学和微生物机制。通过该建议获得的重要知识将有助于定义特定的治疗方法，以更好地控制疾病进展并防止易感人群的疾病开始。