Core 1: Clinical and Biological Specimen Core

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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.