Clinical and Biorepository Core

摘要 系统性硬化症（systemic sclerosis，SSc）是最致命的自身免疫性疾病。SSc相关的主要原因 死亡率是间质性肺病（ILD）和肺动脉高压（PAH）的并发症， 皮肤病是发病的重要原因。利用现有的优势， 匹兹堡大学内的多个部门和学校，核心B是提供资源的关键， 专业知识和支持，以帮助协同研究项目的整体计划目标，研究SSc及其 在拟定的转化研究项目中，ILD、PAH和皮肤增厚的重要并发症。在 为了实现这一目标，核心B具有以下四个具体目标：目标1：提供一个临床数据存储库 随访SSc患者的血液和皮肤生物标本，以支持项目 #1，#2，#3。这将使用长期和公认的匹兹堡大学观察SSc队列 临床和匹配血清数据库。这一40年的观察队列将促进两个交叉的联系， 用于机制研究和统计建模的生物样本的截面和纵向临床数据。目的 2：为了丰富我们现有的肺和皮肤组织、细胞、精密切片和血清库， 正常个体和患有SSc的个体用于项目#1、#2和#3中的应用。在这个目标皮肤从 弥漫性SSc患者，接受肺移植的SSc患者的肺组织以及皮肤和肺 健康对照/供体将经历最先进的分子生物学分析，尤其是单细胞分析， 组织病理学表征，以及细胞和组织模型生成，其将用于支持所有三个 科学项目。目标3：协助项目#1、#2和#3的项目调查员设计和 使用生物样本库中的生物样本和模型进行实验。核心B将提供 在开发和标准化新的协议和技术的专业知识，为细胞和组织为基础的ex 体内模型，实施适当的设置，以确保成功评估机制途径， SSc的治疗干预，并进行金标准SSc特异性血清自身抗体检测， 纳入统计分析。目标4：为项目1、2和3的研究者提供统计数据， 成功完成临床数据的分析和链接所需的支持。

ABSTRACT Systemic sclerosis (SSc) is the most lethal of the autoimmune diseases. The primary causes of SSc-related mortality are the complications of interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), with skin disease being a significant contributor to morbidity. Using the complimentary and existing strengths of multiple divisions and Schools within the University of Pittsburgh, Core B is crucial to providing the resources, expertise and support to help the overall program goal of synergistic research projects studying SSc and its important complications of ILD, PAH and skin thickening in the proposed translational research program. In order to accomplish this, Core B has the following four Specific Aims: Aim 1: To provide a clinical data repository of longitudinally-followed SSc patients to accompany the blood and skin biologic specimens to support Projects #1, #2, and #3. This will use the longstanding and recognized University of Pittsburgh observational SSc cohort clinical and matching serum databank. This 40-year observational cohort will facilitate the linking of both cross- sectional and longitudinal clinical data with biospecimens for mechanistic studies and statistical modeling. Aim 2: To enrich our current repository of lung and skin tissue, cells, precision cut slices, and serum procured from normal individuals and individuals with SSc for application in Projects #1, #2, and #3. In this Aim skin from patients with diffuse SSc, explanted lung tissue from SSc patients undergoing lung transplant and skin and lung healthy controls/donors will undergo state-of the art molecular biological analysis, especially single cell analysis, histopathological characterization, and cell and tissue model generation which will be used to support all three scientific projects. Aim 3: To assist program investigators from Projects #1, #2, and #3 in the design and implementation of experiments using biological specimens and models from the Biobank. Core B will provide expertise in the development and standardization of new protocols and technique for cell and tissue-based ex vivo models, implement proper setups to ensure the successful evaluation of mechanistic pathways and therapeutic interventions for SSc, and perform gold standard SSc-specific serum autoantibody testing to be included in statistical analysis. Aim 4: To provide the investigators in Projects #1, #2 and #3 with the statistical support required to successfully complete the analyses and linking of clinical data.