Clinical and Biorepository Core

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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.