ORAL INFECTION AND INFLAMMATION IN TRANSPLANT PATIENTS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，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。这些口腔感染通常是无症状的，因此可能无法得到诊断和治疗。实体器官移植接受者代表了慢性免疫抑制患者群体的增长，他们的口腔健康状况在很大程度上是未知的。由于最近的研究表明，慢性口腔感染可引发可能导致血管疾病的低度全身炎症，并且由于慢性移植物血管炎可导致移植排斥反应，因此迫切需要对该患者群体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）是公认的全身性炎症的敏感标志物，在慢性牙周炎患者中已被证实升高，也是移植排斥反应的良好诊断指标。在本研究中，我们假设在患有念珠菌性口腔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）与慢性同种异体移植物移植失败相关。为了探讨慢性口腔机会性感染与慢性移植排斥反应之间的潜在关系，我们建议：a)研究口腔念珠菌病和慢性牙周炎在患者群体中的患病率；B)收集关于这些口腔机会性感染与慢性排斥史之间可能存在关联的初步数据；c)检测移植患者血清IL-6和CRP水平，研究其与口腔感染的关系；ii)口腔黏膜IL-6原位表达水平。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系统性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.