ArticleArthritis & rheumatology (Hoboken, N.J.)2015
A longitudinal biomarker for the extent of skin disease in patients with diffuse cutaneous systemic sclerosis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis 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
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- A Functional Genomic Meta-Analysis of Clinical Trials in Systemic Sclerosis: Toward Precision Medicine and Combination Therapy.The Journal of investigative dermatology · 2017Pooled it
- Biological and clinical insights from a randomized phase 2 study of an anti-oncostatin M monoclonal antibody in systemic sclerosis.Rheumatology (Oxford, England) · 2022Trial
- Tofacitinib blocks IFN-regulated biomarker genes in skin fibroblasts and keratinocytes in a systemic sclerosis trial.JCI insight · 2022Trial
- Inhibition of β-Catenin Signaling in the Skin Rescues Cutaneous Adipogenesis in Systemic Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial of C-82.The Journal of investigative dermatology · 2017Trial
- Multiplex serum protein analysis reveals potential mechanisms and markers of response to hyperimmune caprine serum in systemic sclerosis.Arthritis research & therapy · 2017Trial
- Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients.The Journal of clinical investigation · 2015Trial
- Beyond polarization: a receptor-centered framework for macrophage function and therapy in skin diseases.Clinical and experimental medicine · 2026Review
- Altered AP-1, RUNX, and EGR chromatin dynamics drive human fibrotic lung disease.Annals of the rheumatic diseases · 2026Article
- Identifying common genes and immune infiltration characteristics between systemic sclerosis and atherosclerosis.Clinical rheumatology · 2025Article
- Biological hallmarks of systemic sclerosis are present in the skin and serum of patients with Very Early Diagnosis of Systemic Sclerosis (VEDOSS).Rheumatology (Oxford, England) · 2025Article
- Neural network analysis as a novel skin outcome in a trial of belumosudil in patients with systemic sclerosis.Arthritis research & therapy · 2025Article
- Unique and shared transcriptomic signatures underlying localized scleroderma pathogenesis identified using interpretable machine learning.JCI insight · 2025Article
- Precision Medicine in Rheumatology: The Role of Biomarkers in Diagnosis and Treatment Optimization.Journal of clinical medicine · 2025Review
- Article
- Article
- Single-cell transcriptomes and chromatin accessibility of endothelial cells unravel transcription factors associated with dysregulated angiogenesis in systemic sclerosis.Annals of the rheumatic diseases · 2024Article
- Characterization of Endothelial Cell Subclusters in Localized Scleroderma Skin with Single-Cell RNA Sequencing Identifies NOTCH Signaling Pathway.International journal of molecular sciences · 2024Article
- SLIDE: Significant Latent Factor Interaction Discovery and Exploration across biological domains.Nature methods · 2024Article
- Identification of Fibroinflammatory and Fibrotic Transcriptomic Subsets of Human Cutaneous Sclerotic Chronic Graft-Versus-Host Disease.JID innovations : skin science from molecules to population health · 2024Article
- MS4A superfamily molecules in tumors, Alzheimer's and autoimmune diseases.Frontiers in immunology · 2024Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveTo define a pharmacodynamic biomarker based on gene expression in skin that would provide a biologic measure of the extent of disease in patients with diffuse cutaneous systemic sclerosis (dcSSc) and could be used to monitor skin disease longitudinally.
methodsSkin biopsy specimens obtained from a cohort of patients with dcSSc (including longitudinal specimens) were analyzed by microarray. Expression of genes correlating with the modified Rodnan skin thickness score (MRSS) were examined for change over time using a NanoString platform, and a generalized estimating equation (GEE) was used to define and validate longitudinally measured pharmacodynamic biomarkers composed of multiple genes.
resultsMicroarray analysis of genes parsed to include only those correlating with the MRSS revealed prominent clusters of profibrotic/transforming growth factor β-regulated, interferon-regulated/proteasome, macrophage, and vascular marker genes. Using genes changing longitudinally with the MRSS, we defined 2 multigene pharmacodynamic biomarkers. The first was defined mathematically by applying a GEE to longitudinal samples. This modeling method selected cross-sectional THBS1 and longitudinal THBS1 and MS4A4A. The second model was based on a weighted selection of genes, including additional genes that changed statistically significantly over time: CTGF, CD163, CCL2, and WIF1. In an independent validation data set, biomarker levels calculated using both models correlated highly with the MRSS.
conclusionSkin gene expression can be used effectively to monitor changes in SSc skin disease over time. We implemented 2 relatively simple models on a NanoString platform permitting highly reproducible assays that can be applied directly to samples from patients or collected as part of clinical trials.
Indexed as
Identifiers
What OpenQuestion holds
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.