Oral infection and inflammation in transplant patients

描述(申请人提供)：慢性牙周炎和口腔念珠菌病是最常见的与疾病或治疗引起的免疫抑制有关的机会性口腔感染。这些口腔感染通常是无症状的，因此可能仍未得到诊断和治疗。固体器官移植接受者代表着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特征性。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，而且慢性移植物血管炎可导致移植排斥反应，因此迫切需要研究这类患者的口腔和全身炎症状态。血清白介素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。在这项建议中，我们假设在患有复发性念珠菌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该患者群体中的患病率；b)收集这些口腔机会性感染的存在与慢性排斥病史之间的可能联系的初步数据；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；ii)口腔黏膜IL-6的原位表达水平；以及iii)慢性移植排斥史之间的关系。从本文提出的研究中收集的初步数据将对设计未来5年的大规模前瞻性研究至关重要，该研究将在口腔机会性感染、全身炎症和慢性移植排斥反应的发生率之间建立明确的联系。

DESCRIPTION (provided by applicant): 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 immunossuppressed 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 for 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 recurrent Candida stomatitis or chronic periodontitis, chronic elevation of serum IL-6 may directly or indirectly (via induction of CRP) be associated with chronic 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 this patient 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; ii) the levels of oral mucosal IL-6 expression in situ; and iii) the history of chronic transplant rejection. Preliminary data collected from the studies proposed herein will be crucial in designing a future large scale prospective 5-year study which will establish a definitive association between the incidence of oral opportunistic infection, systemic inflammation and chronic transplant rejection.