Biologic Basis of Refractory Periodontal Disease

描述：本研究的长期目标是能够适当地

DESCRIPTION: The long-term goal of this research is to be able to appropriately diagnose and successfully treat all patients with periodontal disease. Currently, about 15 percent of periodontitis patients fail conventional therapy and are deemed "refractory." This application examines the hypothesis that refractory disease is distinct from non-refractory periodontal disease, and seeks means for prospectively identifying these patients. These objectives are addressed in 4 Specific Aims. Aim I will test the hypothesis that subjects with refractory disease can be distinguished from subjects with treatable periodontitis and periodontal health based upon microbial profiles. Subgingival plaque samples will be taken from 28 sites from at least 80 subjects in each of the 2 diseased groups and 40 healthy subjects. The samples will be analyzed individually for levels of approximately 120 taxa using checkerboard DNA hybridization assays. Herpes viruses will also be monitored. The SIGNIFICANCE of this Aim is that it will identify those species (both cultivable and presently uncultivable) that are useful for distinguishing between refractory and treatable periodontitis, and health. Aim 2 will test the hypothesis that subjects with refractory disease can be distinguished from those with treatable periodontitis, and periodontal health based upon host factors, such as serum antibody levels to 40 specific periodontal bacteria and cytokine production by peripheral blood monocytes following stimulation. The SIGNIFICANCE of this Aim is the identification of key host markers that differentiate between disease groups and health. Aim 3 will develop a Human Oral Microbe Microarray for the detection of 600 cultivable and uncultivable oral species found in the human oral cavity. The microbial samples from Aim 1 will be reanalyzed using the essentially complete microbial coverage provided by this microarray. This microarray will facilitate other research efforts in oral ecology, infectious diseases, and clinical studies. The microarray has obvious diagnostic value. Aim 4 will use the combined clinical, microbial and host data to differentiate refractory periodontitis from treatable periodontitis or health, and to identify refractory syndromes. Completion of this project will fill in major gaps in knowledge of the role of the total oral flora in refractory and treatable periodontitis, and of the role of cytokines, chemokines and their receptors. Eliminating refractory disease would have an enormous impact on the total cost of delivering periodontal therapy.