ORAL INFECTION AND INFLAMMATION IN TRANSPLANT PATIENTS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 慢性牙周炎和口腔念珠菌病是最常见的机会性口腔感染，与疾病或治疗引起的免疫抑制有关。这些口腔感染通常无症状，因此可能无法诊断和治疗。实体器官移植受者代表了越来越多的慢性免疫抑制患者，他们的口腔健康状况在很大程度上没有得到表征。由于最近的研究表明，慢性口腔感染可引发低度全身性炎症，这可能有助于血管疾病，因为慢性移植血管炎可导致移植排斥反应，因此迫切需要对该患者人群的口腔和全身炎症状态进行研究。血清白细胞介素-6（IL-6）和C反应蛋白（CRP）是公认的全身炎症的敏感标志物，已被证明在慢性牙周炎患者中升高，也是移植排斥反应的良好诊断指标。在这个建议中，我们假设在念珠菌性口炎或慢性牙周炎的移植患者中，血清IL-6的慢性升高可能直接或间接（通过诱导CRP）与慢性移植物同种异体移植失败有关。 为了开始探索慢性口腔机会性感染和慢性移植排斥反应之间的潜在关系，我们建议a）研究其患者人群中口腔念珠菌病和慢性牙周炎的患病率; B）收集这些口腔机会性感染的存在和慢性排斥反应史之间可能相关性的初步数据;和c）测定移植患者血清中IL-6和CRP的水平，并研究它们与i）口腔感染的存在;和ii）口腔粘膜IL-6原位表达水平的关系。本文提出的试点工作将为设计更大规模的前瞻性临床研究提供框架，该研究将最终解决口腔机会性感染在该特殊需求患者人群中的全身炎症和慢性移植排斥反应中的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic periodontitis and oral candidiasis are the most frequent opportunistic oral infections associated with immunosuppression caused by disease or treatment. These oral infections are frequently asymptomatic and therefore can remain undiagnosed and untreated. Solid organ transplant recipients represent a growing population of chronically immunosuppressed patients whose oral health status has been largely uncharacterized. Because recent studies have shown that chronic oral infection can trigger low grade systemic inflammation which may contribute to vascular disease and because chronic graft vasculitis can lead to transplant rejection, studies characterizing the oral and systemic inflammatory status in this patient population are urgently needed. Serum interleukin-6 (IL-6) and C-reactive protein (CRP) are well established, sensitive markers of systemic inflammation which have been shown to be elevated in chronic periodontitis patients and are also good diagnostic indicators for transplant rejection. In this proposal we hypothesize that in transplant patients with Candida stomatitis or chronic periodontitis, chronic elevation of serum IL-6 may directly or indirectly (via induction of CRP) be associated with chronic graft allograft failure. To begin to explore a potential relationship between chronic oral opportunistic infection and chronic transplant rejection we propose to a) study the prevalence of oral candidiasis and chronic periodontitis in their patients population; b) collect preliminary data on a possible association between the presence of these oral opportunistic infections and a history of chronic rejection; and c) determine the levels of IL-6 and CRP in the serum of transplant patients and study their relationship with i) the presence of oral infection; and ii) the levels of oral mucosal IL-6 expression in situ. The pilot work proposed herein will provide the framework for the design of a larger scale prospective clinical study which will conclusively address the role of oral opportunistic infections in systemic inflammation and chronic transplant rejection in this special needs patient population.