Large-scale analysis of longitudinal skin gene expression in systemic sclerosis reveals relationships of immune cell and fibroblast activity with skin thickness and a trend towards normalization over time

339 total forearm skin biopsies were obtained from 113 unique SSc patients and 44 matched healthy controls. 105 SSc patients had a 2nd biopsy, 76 patients had a 3rd biopsy, and 1 patient had a 4th biopsy. Global gene expression profiling was performed, and differentially expressed genes and cell type-specific signatures in SSc were evaluated for relationships to skin thickness and other clinical variables. Changes in skin gene expression over time were analyzed by mixed effects models and principal component analysis. Immunohistochemical staining was performed to validate conclusions. Skin thickness in SSc is related to dysregulated immune cell and fibroblast gene expression. Skin gene expression changes over time in early diffuse SSc, with a tendency towards normalization. 339 total forearm skin biopsies were obtained from 113 unique SSc patients and 44 matched healthy controls. 105 SSc patients had a 2nd biopsy, 76 patients had a 3rd biopsy, and 1 patient had a 4th biopsy. Global gene expression profiling was performed.