Core 1: Clinical and Biological Specimen Core

临床核心的基本功能是提供前瞻性收集的纵向临床数据和 系统性硬化症(SSC)患者队列的相关生物样本。这一临床数据 将在日期之前与完成项目所必需的生物标本联系起来。临床核心 将建立在现有的两个专门的硬皮病中心纵向SSC患者队列的基础上 匹兹堡和波士顿大学医学中心，以实现这一目标。这些观察队列 将招募连续出现在每个机构的SSC患者。队列数据库将在 UPMC风湿病数据管理系统(RDMS)血清、血浆和PBMC的血液样本 核糖核酸将在临床就诊时获得，并与临床数据联系起来，以支持所有项目。皮肤活检将会是 从弥漫性皮肤SSC患者采集的单细胞RNA-SEQ及其预后的研究 皮肤生物标记物(项目1)。右心导管术患者的导管提示及相关 临床信息，包括右心血流动力学，将被收集来表征内皮细胞。 SSC合并肺动脉高压患者(项目2)。在具体目标1中，临床核心将继续 在双中心观察性临床数据存储库中收集临床数据并协调数据收集 SSC患者，支持项目#1、#2和#3。这些临床数据将在每个SSC前瞻性地收集 中心诊所就诊。将提供与SSC患者组织或血液时间相对应的临床数据 样本确认。临床数据将包括病史、SSC相关症状、体检、 客观测试和患者报告结果(PRO)。在特定目标2中，核心将提供血液、皮肤和 肺血管生物标本伴随SSc相关自身抗体的金标准试验 项目#1、#2和#3。临床核心将促进将临床数据在以下两个横断面(如 第一次SSC诊所就诊)或纵向方式，从而检查项目机械性发现(蛋白质或 M RNA水平)与纵向疾病评估(药效学生物标志物)相关，或与 疾病从最初的生物学评估(预后生物标记物)的变化。UPMC硬皮病 中心是历史上唯一能够完成所有黄金标准SSC的专用SSC中心- 相关自身抗体检测。因此，临床核心将帮助项目调查人员评估 患者自身抗体状态与临床生物学转归的关系。在特定目标中3 临床核心将为项目1、2和3中的项目调查人员提供统计支持 有必要调查临床数据与所提出的机制和预后之间的联系 对所有三个项目的分析。

The essential function of the Clinical Core is to provide prospectively collected, longitudinal clinical data and associated biosamples on a well-characterized cohort of systemic sclerosis (SSc) patients. This clinical data will be linked by date to the biologic specimens essential to the completion of the projects. The Clinical Core will build on two existing, dedicated Scleroderma Center longitudinal SSc patient cohorts at the University of Pittsburgh and Boston University Medical Center in order to accomplish this goal. These observational cohorts will enroll consecutive SSc patients presenting to each institution. Cohort databases will be combined in the UPMC Rheumatic Disease Data Management System (RDMS). Blood samples for serum, plasma and PBMC RNA will be obtained at clinical visits, and linked to clinical data to support all projects. Skin biopsies will be collected from patients with diffuse cutaneous SSc for single cell RNA-seq and development of a prognostic skin biomarker (Project #1). Catheter tips from patients undergoing right heart catheterization and associated clinical information, including right heart hemodynamics, will be collected to characterize endothelial cells from SSc patients with pulmonary arterial hypertension (Project #2). In specific aim 1 the Clinical Core will continue collecting clinical data and harmonize data collection in a two-center observational, clinical data repository of SSc patients, supporting Projects #1, #2 and #3. This clinical data will be collected prospectively at each SSc Center clinic visit. Clinical data will be available corresponding to the time of SSc patient tissue or blood sample ascertainment. Clinical data will include medical history, SSc-related symptoms, physical examination, objective testing and patient reported outcomes (PROs). In specific aim 2 the core will provide blood, skin and pulmonary vascular biospecimens, accompanied by full SSc-associated autoantibody gold standard testing for Projects #1, #2 and #3. The Clinical Core will facilitate linking the clinical data in either cross-sectional (such as first SSc clinic visit) or longitudinal fashion, and thus examine whether project mechanistic findings (protein or mRNA levels) correlate with longitudinal disease assessments (pharmacodynamic biomarkers), or with the change in disease from the initial biological assessment (prognostic biomarkers). The UPMC Scleroderma Center is the only dedicated SSc Center that has historically been able to complete all gold standard SSc- associated autoantibody testing. Thus, the Clinical Core will help project investigators to assess the relationship between the patients' autoantibody status, and clinical and biological outcomes. In specific aim 3 the Clinical Core will provide project investigators in Projects #1, #2 and #3 with the statistical support necessary to investigate associations between the clinical data with the proposed mechanistic and prognostic analyses of all three Projects.