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， 相关的生物样品上的系统性硬化症（SSc）患者的良好表征的队列。本临床数据 将按日期与完成项目所必需的生物标本联系起来。临床核心 将建立在两个现有的，专门的硬皮病中心纵向SSc患者队列在大学 匹兹堡和波士顿大学医学中心，以实现这一目标。这些观察性队列 将入组在每个机构就诊的连续SSc患者。队列数据库将合并到 UPMC风湿病数据管理系统（RDMS）。用于血清、血浆和PBMC的血样 RNA将在临床访视时获得，并与临床数据相关联，以支持所有项目。皮肤活检将 从弥漫性皮肤SSc患者中收集，用于单细胞RNA-seq和发展预后 皮肤生物标志物（项目#1）。接受右心导管插入术的患者的导管尖端和相关 将收集包括右心血流动力学在内的临床信息，以表征 肺动脉高压SSc患者（项目#2）。在具体目标1中，临床核心将继续 收集临床数据，并在双中心观察性临床数据储存库中协调数据收集， SSc患者，支持项目1、2和3。将在每个SSc前瞻性收集该临床数据 中心门诊访视。将提供与SSc患者组织或血液采集时间相对应的临床数据 样品测定临床数据将包括病史、SSC相关症状、体格检查， 客观测试和患者报告结果（PRO）。在具体目标2中，核心将提供血液、皮肤和 肺血管生物标本，伴随完整的Ssc相关自身抗体金标准检测， 项目#1、#2和#3。临床核心将有助于在任一横截面（如 第一次SSc临床访问）或纵向方式，从而检查是否项目机制的结果（蛋白质或 mRNA水平）与纵向疾病评估（药效学生物标志物）相关，或与 从初始生物学评估（预后生物标志物）的疾病变化。UPMC硬皮病 中心是历史上唯一能够完成所有金标准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研究人员评估 患者自身抗体状态与临床和生物学结局之间的关系。具体目标3 临床中心将为项目1、2和3的项目研究者提供统计支持 有必要研究临床数据与拟议的机制和预后之间的关联 分析了三个项目。

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.