Trial reportPloS one2015
Experimentally-derived fibroblast gene signatures identify molecular pathways associated with distinct subsets of systemic sclerosis patients in three independent cohorts.
Trial report in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 3 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- A genomic meta-analysis of clinical variables and their association with intrinsic molecular subsets in systemic sclerosis.Rheumatology (Oxford, England) · 2022Pooled it
- Pooled it
- A Functional Genomic Meta-Analysis of Clinical Trials in Systemic Sclerosis: Toward Precision Medicine and Combination Therapy.The Journal of investigative dermatology · 2017Pooled it
- Machine-learning classification identifies patients with early systemic sclerosis as abatacept responders via CD28 pathway modulation.JCI insight · 2022Trial
- Therapeutic interleukin-6 blockade reverses transforming growth factor-beta pathway activation in dermal fibroblasts: insights from the faSScinate clinical trial in systemic sclerosis.Annals of the rheumatic diseases · 2018Trial
- Nilotinib (Tasigna™) in the treatment of early diffuse systemic sclerosis: an open-label, pilot clinical trial.Arthritis research & therapy · 2015Trial
- Lipodystrophy and adipose tissue recovery are mediated by the Wnt/lipogenesis axis during skin fibrosis.The Journal of pathology · 2026Article
- DPP4 Substrate Supplementation Protects From WNT-Induced Lipid Depletion in Dermal Adipocytes.Experimental dermatology · 2026Article
- Proceedings of the 2Mediterranean journal of rheumatology · 2026Article
- Multimodal analyses of early, untreated systemic sclerosis skin identify a proinflammatory vascular niche of macrophage-fibroblast signaling.JCI insight · 2026Article
- Escape From X Chromosome Inactivation as a Driver of Plasmacytoid DC Heterogeneity in Health and Disease.Immunological reviews · 2025Review
- Fibrotic Disease of the Skin and Lung: Shared Pathways, Environmental Drivers, and Therapeutic Opportunities in a Changing Climate.International journal of molecular sciences · 2025Review
- Wnt Activation in Mature Dermal Adipocytes Leads to Lipodystrophy and Skin Fibrosis via ATGL-Dependent Lipolysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Altered X-chromosome inactivation of the TLR7/8 locus and heterogeneity of pDCs in systemic sclerosis.The Journal of experimental medicine · 2025Article
- Characteristics of skin microbiome associated with disease severity in systemic sclerosis.Journal of microbiology (Seoul, Korea) · 2025Article
- Three Distinct Transcriptional Profiles of Monocytes Associate with Disease Activity in Scleroderma Patients.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Alterations of the Primary Cilia Gene SPAG17 and SOX9 Locus Noncoding RNAs Identified by RNA-Sequencing Analysis in Patients With Systemic Sclerosis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Perspective to precision medicine in scleroderma.Frontiers in immunology · 2023Article
- Tenascin-C in fibrosis in multiple organs: Translational implications.Seminars in cell & developmental biology · 2022Review
- Integrated analysis of dermal blister fluid proteomics and genome-wide skin gene expression in systemic sclerosis: an observational study.The Lancet. Rheumatology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Genome-wide expression profiling in systemic sclerosis (SSc) has identified four 'intrinsic' subsets of disease (fibroproliferative, inflammatory, limited, and normal-like), each of which shows deregulation of distinct signaling pathways; however, the full set of pathways contributing to this differential gene expression has not been fully elucidated. Here we examine experimentally derived gene expression signatures in dermal fibroblasts for thirteen different signaling pathways implicated in SSc pathogenesis. These data show distinct and overlapping sets of genes induced by each pathway, allowing for a better understanding of the molecular relationship between profibrotic and immune signaling networks. Pathway-specific gene signatures were analyzed across a compendium of microarray datasets consisting of skin biopsies from three independent cohorts representing 80 SSc patients, 4 morphea, and 26 controls. IFNα signaling showed a strong association with early disease, while TGFβ signaling spanned the fibroproliferative and inflammatory subsets, was associated with worse MRSS, and was higher in lesional than non-lesional skin. The fibroproliferative subset was most strongly associated with PDGF signaling, while the inflammatory subset demonstrated strong activation of innate immune pathways including TLR signaling upstream of NF-κB. The limited and normal-like subsets did not show associations with fibrotic and inflammatory mediators such as TGFβ and TNFα. The normal-like subset showed high expression of genes associated with lipid signaling, which was absent in the inflammatory and limited subsets. Together, these data suggest a model by which IFNα is involved in early disease pathology, and disease severity is associated with active TGFβ signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.