ArticleArthritis & rheumatology (Hoboken, N.J.)2015
Neutrophil-Related Gene Expression and Low-Density Granulocytes Associated With Disease Activity and Response to Treatment in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
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 81 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 136 citations in OpenAlex.
- Non-invasive biomarkers of disease activity and organ damage in ANCA-associated vasculitis: a systematic review.RMD open · 2024Pooled it
- Neutrophil Extracellular Traps (NETs) and Vasculitis.International journal of medical sciences · 2021Pooled it
- Identification of Novel Low-Density Neutrophil Markers Through Unbiased High-Dimensional Flow Cytometry Screening in Non-Small Cell Lung Cancer Patients.Frontiers in immunology · 2021Trial
- Neutrophil subsets and their gene signature associate with vascular inflammation and coronary atherosclerosis in lupus.JCI insight · 2018Trial
- Reanalysis of the Rituximab in ANCA-Associated Vasculitis trial identifies granulocyte subsets as a novel early marker of successful treatment.Arthritis research & therapy · 2015Trial
- Article
- Anti-neutrophil cytoplasmic antibody-associated vasculitis: biological insights and biomarker-guided disease management.Nature reviews. Nephrology · 2026Review
- Advances in the study of low-density neutrophils in rheumatic diseases.Frontiers in immunology · 2026Review
- Can we cure vasculitis?Current opinion in immunology · 2025Review
- Neutrophils and Platelets as Key Players in the Pathogenesis of ANCA-Associated Vasculitis and Potential Sources of Disease Activity Biomarkers.Diagnostics (Basel, Switzerland) · 2025Review
- Immune cell aberrations in Systemic Lupus Erythematosus: navigating the targeted therapies toward precision management.Cellular & molecular biology letters · 2025Review
- Neutrophils and NETs in kidney disease.Nature reviews. Nephrology · 2025Review
- Interaction of low-density neutrophils with other immune cells in the mechanism of inflammation.Molecular medicine (Cambridge, Mass.) · 2025Review
- Review
- The evolving landscape of vasculitis management: past, current and emerging.Rheumatology (Oxford, England) · 2025Review
- Low-Density Neutrophils: Enigmatic Cells in Health and Disease.Journal of immunology research · 2025Review
- Neutrophil extracellular traps in homeostasis and disease.Signal transduction and targeted therapy · 2024Review
- Immune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis.Nature communications · 2024Article
- Emergence of dysfunctional neutrophils with a defect in arginase-1 release in severe COVID-19.JCI insight · 2024Article
- The Phenotypes and Functions of Neutrophils in Systemic Sclerosis.Biomolecules · 2024Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 11 institutions in 2 countries.
Funding
Abstract
objectiveTo discover biomarkers involved in the pathophysiology of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and to determine whether low-density granulocytes (LDGs) contribute to gene expression signatures in AAV.
methodsThe source of clinical data and linked biologic specimens was a randomized controlled treatment trial in AAV. RNA sequencing of whole blood from patients with AAV was performed during active disease at the baseline visit and during remission 6 months later. Gene expression was compared between patients who met versus those who did not meet the primary trial outcome of clinical remission at 6 months (responders versus nonresponders). Measurement of neutrophil-related gene expression was confirmed in peripheral blood mononuclear cells (PBMCs) to validate the findings in whole blood. A negative-selection strategy isolated LDGs from PBMC fractions.
resultsDifferential expression between responders (n = 77) and nonresponders (n = 35) was detected in 2,346 transcripts at the baseline visit (P < 0.05). Unsupervised hierarchical clustering demonstrated a cluster of granulocyte-related genes, including myeloperoxidase (MPO) and proteinase 3 (PR3). A granulocyte multigene composite score was significantly higher in nonresponders than in responders (P < 0.01) and during active disease than during remission (P < 0.01). This signature strongly overlapped an LDG signature identified previously in lupus (false discovery rate by gene set enrichment analysis <0.01). Transcription of PR3 measured in PBMCs was associated with active disease and treatment response (P < 0.01). LDGs isolated from patients with AAV spontaneously formed neutrophil extracellular traps containing PR3 and MPO.
conclusionIn AAV, increased expression of a granulocyte gene signature is associated with disease activity and decreased response to treatment. The source of this signature is likely LDGs, a potentially pathogenic cell type in AAV.
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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.