ArticleThe New England journal of medicine2014
Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis.
Article in The New England journal of medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03059979 (Hit Hard and Early. The Effect of High Dose Methylprednisolone on Nailfold Capillary Changes and Biomarkers in Early SSc), which is not on this map. Cited by 246 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Hit Hard and Early. The Effect of High Dose Methylprednisolone on Nailfold Capillary Changes and Biomarkers in Early SSc: a 12-week Randomised Explorative Double-blind Placebo-controlled Trial.
Who cites it
246 citing papers in PubMed, 1 synthesis or guideline pooled it, 451 citations in OpenAlex.
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- Avenciguat: a novel soluble guanylate cyclase activator that affects multiple cell types to inhibit IFN-1 signalling and fibrosis.Rheumatology (Oxford, England) · 2025Trial
- New horizons in systemic sclerosis treatment: advances and emerging therapies in 2025.RMD open · 2025Trial
- Efficacy of methylprednisolone in very early systemic sclerosis: results of the 'Hit Hard and Early' randomized controlled trial.Rheumatology (Oxford, England) · 2025Trial
- Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis.Rheumatology (Oxford, England) · 2024Trial
- Trial
- Insights Into the Role of Platelet Factor 4 in Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2026Review
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- Mechanisms of regeneration and maladaptive repair in acute kidney injury.Nature reviews. Nephrology · 2026Review
- Recent Advances in Biomarkers of Systemic Sclerosis-Associated Interstitial Lung Disease: Clinical Relevance and Therapeutic Perspectives.Life (Basel, Switzerland) · 2026Review
- PF4 drives mechanical overload-induced temporomandibular joint osteoarthritis through TLR2-dependent activation of NF-κB.Journal of translational medicine · 2026Article
- Integrated single-cell transcriptomic analysis identifiesBiochemistry and biophysics reports · 2026Article
- Tetrameric assembly disruption impairs CXCL4 chaperon ability for DNA and type I interferon immune amplification.Communications biology · 2026Article
- Fibrosis-memory is mediated by IL-3-producing T cells and drives progression of fibrosis.The Journal of clinical investigation · 2026Article
- CXCL4 and CXCL4L1 activate human macrophage via TLR4 signaling to modulate inflammatory responses.Cell insight · 2026Article
- Anifrolumab-A Potential New Systemic Sclerosis Treatment.Journal of clinical medicine · 2026Review
- Serum CCL18 May Reflect Multiorgan Involvement with Poor Outcome in Systemic Sclerosis.Biomolecules · 2026Article
- Profibrotic macrophage-derived CXCL4 promotes pericyte-to-myofibroblast transition after spinal cord injury.Journal of orthopaedic translation · 2026Article
- Chimeric antigen receptor T-cell therapy for rheumatic diseases: from B-cell depletion to immune reset and beyond.Frontiers in immunology · 2026Review
- Interferon receptor gene dosage differentially regulates hypoxia-induced platelet activation and pulmonary hypertension in down syndrome.Frontiers in immunology · 2026Article
186 more citing papers are in PubMed but not listed here.
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Authors and funding
45 authors at 10 institutions in 6 countries.
Funding
Abstract
backgroundPlasmacytoid dendritic cells have been implicated in the pathogenesis of systemic sclerosis through mechanisms beyond the previously suggested production of type I interferon.
methodsWe isolated plasmacytoid dendritic cells from healthy persons and from patients with systemic sclerosis who had distinct clinical phenotypes. We then performed proteome-wide analysis and validated these observations in five large cohorts of patients with systemic sclerosis. Next, we compared the results with those in patients with systemic lupus erythematosus, ankylosing spondylitis, and hepatic fibrosis. We correlated plasma levels of CXCL4 protein with features of systemic sclerosis and studied the direct effects of CXCL4 in vitro and in vivo.
resultsProteome-wide analysis and validation showed that CXCL4 is the predominant protein secreted by plasmacytoid dendritic cells in systemic sclerosis, both in circulation and in skin. The mean (±SD) level of CXCL4 in patients with systemic sclerosis was 25,624±2652 pg per milliliter, which was significantly higher than the level in controls (92.5±77.9 pg per milliliter) and than the level in patients with systemic lupus erythematosus (1346±1011 pg per milliliter), ankylosing spondylitis (1368±1162 pg per milliliter), or liver fibrosis (1668±1263 pg per milliliter). CXCL4 levels correlated with skin and lung fibrosis and with pulmonary arterial hypertension. Among chemokines, only CXCL4 predicted the risk and progression of systemic sclerosis. In vitro, CXCL4 down-regulated expression of transcription factor FLI1, induced markers of endothelial-cell activation, and potentiated responses of toll-like receptors. In vivo, CXCL4 induced the influx of inflammatory cells and skin transcriptome changes, as in systemic sclerosis.
conclusionsLevels of CXCL4 were elevated in patients with systemic sclerosis and correlated with the presence and progression of complications, such as lung fibrosis and pulmonary arterial hypertension. (Funded by the Dutch Arthritis Association and others.).
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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.