ArticleAnnals of the rheumatic diseases2022
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 normalisation over time.
Article in Annals of the rheumatic diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Dermal cellular senescence and EndMT in patients with systemic sclerosis undergoing cyclophosphamide or aHSCT treatment.Rheumatology (Oxford, England) · 2025Trial
- Gain of function NOTCH4 variants disrupt angiogenesis in systemic sclerosis.Annals of the rheumatic diseases · 2026Article
- Adipocyte-specific deletion of sine oculis homeobox homolog 1 inhibits lipolysis and reduces skin fibrosis.JCI insight · 2026Article
- Skin Transcriptomics Reveal Shared Molecular Mechanisms for Skin and Lung Involvement in Systemic Sclerosis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Molecular imaging of fibroblast activation in systemic sclerosis using [European journal of nuclear medicine and molecular imaging · 2026Article
- Proceedings of the 2Mediterranean journal of rheumatology · 2026Article
- A compact five-gene immuno-fibrotic profile distinguishing systemic sclerosis subtypes with PXDN validated as a fibrosis-associated target.Frontiers in immunology · 2026Article
- TGF-β1 promotes collagen synthesis in systemic sclerosis via upregulating P4HA3.Journal of translational autoimmunity · 2025Article
- Angiopoietin-like protein 2 mediates vasculopathy-driven fibrogenesis in a mouse model of systemic sclerosis.The Journal of clinical investigation · 2025Article
- Stem cell therapy in systemic sclerosis.Clinical rheumatology · 2025Review
- Lymphomonocytic Extracellular Vesicles Influence Fibroblast Proliferation and Collagen Production in Systemic Sclerosis.International journal of molecular sciences · 2025Article
- An international perspective on the future of systemic sclerosis research.Nature reviews. Rheumatology · 2025Review
- Identification of crosstalk genes and diagnostic biomarkers in systemic sclerosis associated sarcopenia through integrative analysis and machine learning.Frontiers in immunology · 2025Article
- Skin Gene Expression Profiles in Systemic Sclerosis: From Clinical Stratification to Precision Medicine.International journal of molecular sciences · 2023Review
- Immune cell dysregulation as a mediator of fibrosis in systemic sclerosis.Nature reviews. Rheumatology · 2022Review
- Skin involvement in early diffuse cutaneous systemic sclerosis: an unmet clinical need.Nature reviews. Rheumatology · 2022Review
- Toward Molecular Stratification and Precision Medicine in Systemic Sclerosis.Frontiers in medicine · 2022Review
- The Pathophysiological Roles of Regulatory T Cells in the Early Phase of Systemic Sclerosis.Frontiers in immunology · 2022Review
- ALASCA: An R package for longitudinal and cross-sectional analysis of multivariate data by ASCA-based methods.Frontiers in molecular biosciences · 2022Article
- Predicting the Progression of Very Early Systemic Sclerosis: Current Insights.Open access rheumatology : research and reviews · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesDetermine relationships between skin gene expression and systemic sclerosis (SSc) clinical disease features, and changes in skin gene expression over time.
methodsA total of 339 forearm skin biopsies were obtained from 113 SSc patients and 44 matched healthy controls. 105 SSc patients had a second biopsy, and 76 had a third biopsy. Global gene expression profiling was performed, and differentially expressed genes and cell type-specific signatures in SSc were evaluated for relationships to modified Rodnan Skin Score (mRSS) and other clinical variables. Changes in skin gene expression over time were analysed by mixed effects models and principal component analysis. Immunohistochemical staining was performed to validate conclusions.
resultsGene expression dysregulation was greater in SSc patients with affected skin than in those with unaffected skin. Immune cell and fibroblast signatures positively correlated with mRSS. High baseline immune cell and fibroblast signatures predicted higher mRSS over time, but were not independently predictive of longitudinal mRSS after adjustment for baseline mRSS. In early diffuse cutaneous SSc, immune cell and fibroblast signatures declined over time, and overall skin gene expression trended towards normalisation. On immunohistochemical staining, most early diffuse cutaneous SSc patients with high baseline T cell and macrophage numbers had declines in these numbers at follow-up.
conclusionsSkin 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 normalisation. These observations are relevant for understanding SSc pathogenesis and could inform treatment strategies and clinical trial design.
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