NON-INVASIVE APPROACHES TO ASSESSING INFLAMMATION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心，不一定是研究者所在机构。描述（由申请人提供）： 尽管在更好地理解慢性炎症性疾病的免疫调节和遗传易感性机制方面取得了重大进展，包括免疫介导的关节炎、糖尿病、炎症性肠病、系统性红斑狼疮（SLE）、肾小球肾炎、血管炎、动脉粥样硬化和哮喘，其诊断和临床管理的主要障碍是不能容易地确定和量化疾病的活动和程度，在可触及的内部器官中。此外，目前的技术不能识别亚临床炎症，其预测在诱导缓解后症状的快速复发或高风险个体中疾病的开始。肠、肺、肝、肾、关节、血管、甲状腺和脑中疾病活动的组织学诊断和评估需要侵入性内窥镜、经皮或甚至开放式手术活检，这带来相当大的不适和风险。 我们的目标是开发非侵入性的方法来确定炎症的位置和强度，在不可接近的器官的患者与几种炎症性疾病的基础知识，血管内皮/效应炎症细胞相互作用的机制，激活先天性和获得性免疫细胞，血管通透性和新血管形成的新的成像技术。我们的研究将集中在克罗恩病，溃疡性结肠炎，系统性红斑狼疮，抗中性粒细胞胞浆抗体（ANCA）介导的血管炎和动脉粥样硬化，因为跨学科的研究计划，包括基本机制，动物模型和临床研究，在这些疾病存在于我们的机构，每一个是多器官条件，这些疾病的原型T淋巴细胞，抗体/补体，中性粒细胞和巨噬细胞介导的疾病，分别因此，这些重点研究的结果将适用于所有先前提到的炎症性疾病。 以下具体目标将接近这一目标：1。建立一个行政结构，规划和协调活动，促进多学科调查员小组之间的有效互动和沟通。2.组织主题驱动的研讨会，促进当地研究人员和外部专家之间的互动，以确定最佳的分子靶点，检测技术和临床应用，以确定各种器官和疾病过程中炎症的程度和活动。3.支持试点研究，以确定分子靶点（第一年），优化成像和分子/生物化学/免疫技术（第一年和第二年），在不同器官的炎症条件的动物模型中验证这些目标和技术（第二年），并应用基础和动物模型研究的结果在靶向人类炎症性疾病中进行试点研究（第三年）。这项转化的临床应用研究将涉及来自3所大学和环境保护局5所学校的9个部门和7个中心的60多名研究人员的多学科互动小组。这种组织良好的规划过程将导致临床相关的结果，可以快速优化应用于多个器官中的许多重要炎症性疾病。该项目将创建一个新的计划，涉及以前没有一起工作过的调查人员，同时建立在机构优势和方案倡议的基础上。

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. DESCRIPTION (provided by applicant): Although significant strides have been made toward better understanding the mechanisms of immunoregulation and genetic susceptibility of chronic inflammatory disorders, includingimmune-mediatedarthritis, diabetes, inflammatory bowel diseases, systemic lupus erythematosus (SLE),glomerulonephritis, vasculitis, atherosclerosis and asthma, a major impediment to their diagnosis and clinical management is the inability to easily determine and quantify the activity and extent of disease involving in accessible internal organs. Moreover, current techniques cannot identify subclinical inflammation that predicts rapid recurrence of symptoms after inducing remission or the on set of disease in high risk individuals. Histologic diagnosis and assessment of disease activity in the intestine, lung, liver, kidney, joint, blood vessels, thyroid and brain, require invasive endoscopic, percutaneous or even open surgical biopsy, which entail considerable discomfort and risk. Our goal is to develop noninvasive methods to determine the location and intensity of inflammation in inaccessible organs of patients with several inflammatory diseases by applying basic knowledge of the mechanisms of vascular endothelial/ effector inflammatory cell interactions, activation of innate and acquired immune cells, vascular permeability and neovascularization to novel imaging techniques. Our studies will focus on Crohn's disease, ulcerative colitis, SLE, anti-neutrophil cytoplasmic antibody (ANCA)-mediated vasculitis and atherosclerosis because interdisciplinary research programs that encompass basic mechanistic, animal model and clinical investigations in these disorders exist in our institution, each are multiorgan conditions, and these diseases are prototypes of T lymphocyte, antibody/complement, neutrophil and macrophage-mediated disorders, respectively. Results from these focused studies will therefore be applicable to all of the previously mentioned inflammatory conditions. The following Specific Aims will approach this goal: 1. Develop an administrative structure that will plan and coordinate activities and promote effective interactions and communication among a multidisciplinary group of investigators. 2. Organize topic-driven workshops promoting interactions between local investigators and external experts to define the optimal molecular targets, detection techniques and clinical applications for determining the extent and activity of inflammation in a variety of organs and disease processes. 3. Support pilot studies to define molecular targets (1st year), optimize imaging and molecular/biochemical/immunologic techniques (1st and 2nd years), validate these targets and techniques in animal models of inflammatory conditions in diverse organs (2nd year), and perform pilot studies in targeted human inflammatory diseases applying the results of the basic and animal model studies (3rd year). This translational, clinically applied research will involve a multidisciplinary, interactive group of >60 investigators derived from 9 departments and 7 centers in 5 schools of 3 universities and the Environmental Protection Agency. This well organized planning process will result in clinically relevant outcomes that can be quickly optimized for application to a number of important inflammatory diseases in multiple organs. This project will create a new program involving investigators who have not previously worked together, while building on institutional strengths and programmatic initiatives.