ArticleThe Journal of clinical investigation2010
Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 2 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
95 citing papers in PubMed, 2 syntheses or guidelines pooled it, 205 citations in OpenAlex.
- Cross-phenotype analysis of Immunochip data identifiesAnnals of the rheumatic diseases · 2018Pooled it
- PTPN22 R620W polymorphism and ANCA disease risk in white populations: a metaanalysis.The Journal of rheumatology · 2015Pooled it
- Current Overview of Multi-omics Analyses in Microscopic Polyangiitis and Granulomatosis with Polyangiitis.Internal medicine (Tokyo, Japan) · 2026Review
- Innate immune cross-talk: The central role of neutrophils and macrophages in ANCA-associated vasculitis.Molecular biology of the cell · 2025Review
- Can we cure vasculitis?Current opinion in immunology · 2025Review
- Immunopathology of Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis.International journal of molecular sciences · 2025Review
- Current Understanding of the Pathogenesis of ANCA-Associated Vasculitis and Novel Treatment Options Targeting Complement Activation.Life (Basel, Switzerland) · 2025Review
- Drug-Induced Renal Vasculitis: Etiology, Pathogenesis, Clinical Manifestations, and Therapeutic Approaches-A Narrative Review.Health science reports · 2025Article
- The evolving landscape of vasculitis management: past, current and emerging.Rheumatology (Oxford, England) · 2025Review
- Childhood-Onset ANCA-Associated Vasculitis: From Genetic Studies to Advances in Pathogenesis, Classification and Novel Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Genetic and Non-Genetic Contributions to Eosinophilic Granulomatosis with Polyangiitis: Current Knowledge and Future Perspectives.Current issues in molecular biology · 2024Review
- Pathogenesis of Pulmonary Manifestations in ANCA-Associated Vasculitis and Goodpasture Syndrome.International journal of molecular sciences · 2024Review
- Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Induced Carcinogenesis and Tumorigenesis by Omega-3 Fatty Acids in Mice In Vivo.International journal of molecular sciences · 2024Article
- Article
- Review
- Article
- Methylation across the central dogma in health and diseases: new therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- New Insights into Pathogenesis and Treatment of ANCA-Associated Vasculitis: Autoantibodies and Beyond.Antibodies (Basel, Switzerland) · 2023Review
- Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis.Rheumatology and immunology research · 2023Review
- PRTN3 variant correlates with increased autoantigen levels and relapse risk in PR3-ANCA versus MPO-ANCA disease.JCI insight · 2023Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Antineutrophil cytoplasmic autoantibody (ANCA) causes vascular injury that leads to small-vessel vasculitis. Patients with ANCA aberrantly express neutrophil granule-encoding genes, including 2 that encode autoantigens: proteinase 3 (PR3) and myeloperoxidase (MPO). To uncover a potential transcriptional regulatory mechanism for PR3 and MPO disrupted in patients with ANCA vasculitis, we examined the PR3 and MPO loci in neutrophils from ANCA patients and healthy control individuals for epigenetic modifications associated with gene silencing. We found that levels of the chromatin modification H3K27me3, which is associated with gene silencing, were depleted at PR3 and MPO loci in ANCA patients compared with healthy controls. Interestingly, in both patients and controls, DNA was unmethylated at a CpG island in PR3, whereas in healthy controls, DNA was methylated at a CpG island in MPO. Consistent with decreased levels of H3K27me3, JMJD3, the demethylase specific for H3K27me3, was preferentially expressed in ANCA patients versus healthy controls. In addition, we describe a mechanism for recruiting the H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) to PR3 and MPO loci mediated by RUNX3. RUNX3 message was decreased in patients compared with healthy controls, and may also be under epigenetic control. DNA methylation was increased at the RUNX3 promoter in ANCA patients. These data indicate that epigenetic modifications associated with gene silencing are perturbed at ANCA autoantigen-encoding genes, potentially contributing to inappropriate expression of PR3 and MPO in ANCA patients.
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.