Mechanisms and Treatment Response of Aggressive Periodontitis in Children

描述(申请人提供)：侵袭性牙周炎(AGP)是一组罕见但严重、进展迅速的牙周炎，其特征是发病年龄早，骨质破坏迅速，导致早期牙齿脱落。看来，这种疾病是由细菌感染和免疫系统过度活跃共同作用的结果。然而，鉴于它的罕见发生和聚集大量人口的困难，关于这种疾病的具体机制和相应的适当治疗的知识仍然建立在病例报告和一些小型临床试验的基础上。在佛罗里达州塔拉哈西，我们已经确定了至少50名在一个临床环境下确诊的非洲裔美国儿童，他们患有非常相似的局部性AGP(LAgP)模式。这一群体代表了佛罗里达州北部服务不足的一小部分人口。我们的初步数据显示，免疫反应加剧，与这种疾病有关的特定细菌群。有了适当的诊断工具和我们在这群人中已经获得的知识，我们相信我们能够聚集更多的人来进一步了解这种侵袭性疾病及其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导致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与高炎性先天特征和一组特定细菌的组合有关，牙周治疗能够调节这些导致组织破坏的参数。为了验证我们的假设，我们建议：1-通过评估导致组织破坏的细胞/趋化因子表达的系统调控机制，确定“传统”牙周治疗是否改变了LAgP中观察到的高反应性特征；2-确定局部炎症介质和金属蛋白酶如何通过LAgP儿童牙周疾病的进展和治疗进行调节；以及3-确定传统牙周治疗后与LAgP相关的牙龈下微生物群的变化。我们希望这项研究的结果将使我们更好地了解儿童牙周组织侵袭性破坏的机制，以及治疗如何影响这些机制。这将使我们能够研究早期和改进的治疗方法，以防止早期牙齿脱落和未来可能出现的全身并发症。 与公共卫生相关：尽管侵袭性牙周炎的发病率很低，但它是一种快速破坏性的牙周病，在很小的时候就开始出现，导致第一磨牙和门牙过早丧失。人们对这种疾病的发病机制知之甚少。了解疾病的发病机制是建立适当的治疗方法的当务之急。我们在表现出类似侵袭性疾病特征的同质人群中建立了一项对照研究，以纵向评估这种疾病的机制。这项研究的目的是确定导致局限性侵袭性牙周炎儿童快速组织破坏的免疫学和微生物学机制，以及常规牙周干预对这些机制的影响。通过这项建议获得的重要知识将有助于确定具体的治疗方法，以更好地控制疾病进展并防止易感个体的疾病起始。

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.