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，鉴于其罕见的发生和难以收集大量的人口，对这种疾病的具体机制和适当治疗的知识仍然基于病例报告和一些小型临床试验。我们在佛罗里达塔拉哈西的一个临床环境中确定了至少50名非裔美国儿童的队列，他们具有非常相似的局部AgP（LAgp）模式。这个群体代表了北佛罗里达的一小部分服务不足的人口。我们的初步数据显示，免疫反应加剧，特定的细菌群与这种疾病有关。有了适当的诊断工具和我们在这一人群中已经获得的知识，我们相信我们能够收集更多的人群，以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，本研究的总体目标是确定哪些机制是导致侵袭性牙周炎儿童组织快速破坏的原因，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与高炎症先天特征和特定细菌群的组合相关，并且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节机制，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。和3-确定传统牙周治疗后与LAgP相关的龈下微生物菌群的变化。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的全身并发症。 公共卫生相关性：侵袭性牙周炎虽然发病率低，但它是一种快速破坏性的牙周病，在年轻时就开始发病，导致第一磨牙和门牙过早脱落。对这种疾病的机制知之甚少。必须了解疾病的机制，以建立适当的治疗方法。我们在一个具有相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。本研究的目的是确定免疫学和微生物学机制负责快速组织破坏的儿童局部侵袭性牙周炎，以及如何传统的牙周干预影响这些机制。从该建议中获得的重要知识将有助于确定特定的治疗方法，以更好地控制疾病进展并预防易感个体的疾病发生。