Cincinnati Multidisciplinary Clinical Research Center

该申请由辛辛那提儿童医院医疗中心提供，是我们现有 P60 多学科临床研究中心拨款的竞争性延续，也是对我们正在进行的 P30 辛辛那提风湿病核心中心拨款的补充。该中心的主要重点是更好地了解儿童风湿性疾病的机制及其治疗。特别强调跨学科互动，利用资源，实现协同效应。提出了四个项目（均不是试点项目）。每个的标题和主要焦点如下。 1) 改进了儿科神经精神系统性红斑狼疮 (NPSLE) 的诊断和先进磁共振成像。该项目的主要目标是开发一种易于使用的神经认知功能障碍 (NCD) 筛查工具，可在常规临床环境中使用，并确定先进成像技术的效用，以加深我们对儿科 SLE 如何影响 CMS 从而导致 NCD 的理解。 2) 加深了对 TNF 抑制在幼年特发性关节炎 (JIA) 中的生物学和应用的了解。这项研究的主要目标是开发方法来准确识别那些在出现良好反应后可以安全停止抗 TNF 治疗的儿童，而不会出现疾病快速发作的风险。这项研究将有助于更好地了解 TNF 拮抗剂疗法对 JIA 生物学的影响，并为使用这些极其重要的新疗法提供更安全、更具成本效益的方法。 3) 系统性幼年特发性关节炎 (sJIA) 中的巨噬细胞激活综合征 (MAS) 生物标志物。该项目将调查 MUNC 13-4 基因的多态性是否会导致 MAS 的易感性，从而帮助识别 MAS 风险较高的儿童。初步证据表明，血清中slL2Ra和sCD163的水平可能反映MAS中T细胞和巨噬细胞的活化和扩增程度，从而可作为早期诊断标志物。此外，我们将研究这些可溶性受体水平的升高是否能够可靠地区分明显和亚临床 MAS 患者与传统 sJIA 耀斑患者。我们将确定那些 MAS 风险增加的人是否代表 sJIA 的一种独特亚型，可以在 sJIA 发病时识别出来。 4) 幼年特发性关节炎儿童健康相关生活质量的决定因素。该项目的主要目的是确定医学变量（生物、生理、临床）和非医学变量（儿童、家庭、环境）预测幼年特发性关节炎儿童 HRQOL 的途径。 成熟的方法核心将为所有四个 MCRC 项目以及研究基地的许多项目提供服务，并作为国家和国际资源。由多个内部和外部顾问委员会组成的行政单位将进行行政和业务监督。

This application, from Cincinnati Children's Hospital Medical Center, is a competing continuation of our existing P60 Multidisciplinary Clinical Research Center grant and is complementary to our ongoing P30 Cincinnati Rheumatic Diseases Core Center grant. The Center's chief focus is a greater understanding of the mechanisms of the rheumatic illnesses of childhood and their treatment. Special emphasis is given to cross-disciplinary interactions, and leveraging of resources such that synergism is realized. Four projects (none of which are pilot projects) are proposed. The titles and chief foci of each are given below. 1) Improved Diagnostic and Advanced Magnetic Resonance Imaging for Pediatric Neuro-Psychiatric SLE (NPSLE). Chief aims of this project are to develop an easy-to-use screening tool for neuro-cognitive dysfunction (NCD) that can be utilized in the routine clinic setting, and to determine the utility of advanced imaging techniques to heighten our understanding of how pediatric SLE affects the CMS, resulting in NCD. 2) Improved Understanding of the Biology and Use of TNF Inhibition in juvenile idiopathic arthritis (JIA). The primary goal of this study is to develop methods to accurately identify those children in whom anti-TNF therapies can be safely stopped after a favorable response, without risk of a rapid disease flare. This study will result in a better understanding of the effect of TNF antagonist therapy on the biology of JIA and a safer and more cost effective approach to the use of these profoundly important new therapies. 3) Macrophage Activation Syndrome (MAS) Biomarkers in Systemic JIA (sJIA). This project will investigate whether polymorphisms in the MUNC 13-4 gene contribute to the predisposition to MAS, thereby helping to identify children at an elevated increased risk of MAS. Preliminary evidence suggests that serum levels of slL2Ra and sCD163 may reflect the degree of activation and expansion of T cells and macrophages in MAS, and thus serve as early diagnostic markers. Further, we will investigate whether elevated levels of these soluble receptors can distinguish reliably between those with overt and sub-clinical MAS from those with conventional sJIA flare. We will determine if those at increased risk of MAS represent a distinct subtype of sJIA which can be recognized at onset of sJIA. 4) Determinants of Health-Related Quality of Life in Children with JIA. The chief aim of this project is to determine the pathways by which medical variables (biological, physiological, clinical) and non-medical variables (child, family, environmental) predict the HRQOL in children being treated for JIA. A well-matured Methodology Core will serve all four MCRC projects, as well as many projects in the research base, and serves as a national and international resource. An Administrative Unit, composed of several internal and external advisory boards, will exercise administrative and operational oversight.