GENETIC AND IMMUNOLOGIC ASPECTS OF PERIODONTAL DISEASES

牙周病的遗传学和免疫学方面的研究。拟议研究的总体目标是通过一种综合的方法来解决牙周学中的重要问题，该方法利用研究人员在人类遗传学、免疫学和细菌发病机制方面的专业知识。参与这些项目的研究人员已经成功合作多年，最近得到了牙周病研究中心NIDR赠款的支持。我们现在建议将一系列项目捆绑在一起作为一个计划项目；我们建议支持一个核心设施，该设施为其他项目提供行政、临床和生物统计学支持。每个项目都将依靠核心来支持其科学目标。提出了四个相互关联和综合的科学项目。多年来，我们一直在研究早发性牙周病(EOP)的遗传学方面，并发现了一个与EOP易感性有关的特定基因(位于染色体2q上的IL-1)和一个染色体区域(19q)。强烈建议增加染色体区域，为继续和扩大这些研究提供了理论基础。其次，我们一直在研究牙周炎患者的抗体反应和免疫球蛋白产生；主要发现是观察到血清IgG2水平是一种可遗传的特征，一些EOP患者的IgG2血清浓度显著高于健康人或AP患者。这些观察形成了一些EOP患者比健康人或AP患者更高的3%的基础。这些观察结果构成了另外3个项目的基础。将研究细胞因子，包括IL-1(参与EOP易感性，其水平由基因决定)和脂质介质(包括PGE2和PAF)对IgG2产生的贡献。此外，我们还将研究PAG调节酶PAG乙酰水解酶的作用，它是由LJP患者的单核细胞在低浓度下产生的。此外，我们还发现，与健康受试者相比，牙周附着丧失的患者抗磷酰胆碱(PC)的IgG2抗体水平升高；这导致我们观察到抗PC抑制IgG2的产生，以及与牙周破坏相关的几种菌斑微生物(放线菌、核杆菌)和乳房内膜炎(S.sanguis)可能存在PC。该a-PC抗体和口腔细菌PC的意义将被检测，并将探索a-PC水平的遗传控制。

Studies of genetic and immunologic aspects of periodontal diseases. The overall goal of the proposed research is to address significant questions in periodontology via an integrated approach that exploits investigator expertise in human genetics, immunology, and bacterial pathogenesis. The investigators participating in these projects have worked together successfully for many years and were most recently supported by a Periodontal Disease Research Center grant form NIDR. We now propose a series of projects tied together as a Program Project; we propose to support a Core facility that provides administrative, clinical, and biostatistical support to the other projects. Each project will rely upon the Core for support of its scientific goals. Four interrelated and integrated scientific projects are proposed. We have been studying genetic aspects of early-onset periodontal diseases (EOP) for several years and have identified a specific gene (IL-1 on chromosome 2q) and a chromosomal region (19q) involved in EOP susceptibility. Additional chromosomal regions are strongly suggested, providing a rationale for continuing and expanding these studies. Secondly, we have been studying antibody responses and immunoglobulin production in periodontitis patients; major findings have been the observations that serum IgG2 levels are a heritable trait, and that IgG2 serum concentrations are significantly higher in some EOP patients than in healthy individuals or AP patients. These observations form the foundation for 3 higher in some EOP patients than in healthy individuals or AP patients. These observations form the foundation for 3 additional projects. The contribution of cytokines, including Il-1 (which is involved in EOP susceptibility, and levels of which are genetically determined), and lipid mediators (including PGE2 and PAF) to IgG2 production will be examined. Further, the contribution of PAG regulatory enzyme PAG acetyl-hydrolase, which is produced in low concentrations by monocytes from LJP patients, will be studied, Additionally, we have discovered that IgG2 antibody levels against phosphorylcholine (PC) are elevated in patients with periodontal attachment loss compared to healthy subjects; this led us to the observations that anti-PC inhibits IgG2 production and that several plaque microorganisms associated with periodontal destruction (A. actinomycetemcomitans, F. nucleatum) and endocaritis (S. sanguis), may have PC. The significance of this a-PC antibody and oral bacterial PC will be examined, and genetic control of a-PC levels will be explored.