ArticleJournal of autoimmunity2016
Targeting downstream transcription factors and epigenetic modifications following Toll-like receptor 7/8 ligation to forestall tissue injury in anti-Ro60 associated heart block.
Article in Journal of autoimmunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Hydroxychloroquine to Prevent Recurrent Congenital Heart Block in Fetuses of Anti-SSA/Ro-Positive Mothers.Journal of the American College of Cardiology · 2020Trial
- Single Cell RNA Sequencing Reveals THBS1+CD14+ Monocyte Modulates Inflammatory Activation via NRLP3-Inflammasome in Congenital Heart Block.Journal of cellular and molecular medicine · 2026Article
- Role of Hydroxychloroquine in Prevention of Congenital Heart Block in Pregnant Women With Positive Anti-Ro/SSA and/or Anti-La/SSB.The Australian & New Zealand journal of obstetrics & gynaecology · 2026Review
- Molecular Mechanisms of Fetal and Neonatal Lupus: A Narrative Review of an Autoimmune Disease Transferal across the Placenta.International journal of molecular sciences · 2024Review
- Autoimmune congenital heart block: a case report and review of the literature related to pathogenesis and pregnancy management.Arthritis research & therapy · 2024Review
- Contribution of S100A4-expressing fibroblasts to anti-SSA/Ro-associated atrioventricular nodal calcification and soluble S100A4 as a biomarker of clinical severity.Frontiers in immunology · 2023Article
- Reducing the burden of surveillance in pregnant women with no history of fetal atrioventricular block using the negative predictive value of anti-Ro/SSA antibody titers.American journal of obstetrics and gynecology · 2022Article
- Hydroxychloroquine Alleviates EAU by Inhibiting Uveitogenic T Cells and Ameliorating Retinal Vascular Endothelial Cells Dysfunction.Frontiers in immunology · 2022Article
- Approaches towards fighting the COVID‑19 pandemic (Review).International journal of molecular medicine · 2021Review
- An Update on the Pathogenesis of Cutaneous Lupus Erythematosus and Its Role in Clinical Practice.Current rheumatology reports · 2020Review
- Common innate pathways to autoimmune disease.Clinical immunology (Orlando, Fla.) · 2020Review
- Interferon pathway in SLE: one key to unlocking the mystery of the disease.Lupus science & medicine · 2019Review
- Type I interferons in host defence and inflammatory diseases.Lupus science & medicine · 2019Review
- Siglec-1 Macrophages and the Contribution of IFN to the Development of Autoimmune Congenital Heart Block.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- The prevention, screening and treatment of congenital heart block from neonatal lupus: a survey of provider practices.Rheumatology (Oxford, England) · 2018Article
- Cardiac fibroblast transcriptome analyses support a role for interferogenic, profibrotic, and inflammatory genes in anti-SSA/Ro-associated congenital heart block.American journal of physiology. Heart and circulatory physiology · 2017Article
- Progress in the pathogenesis and treatment of cardiac manifestations of neonatal lupus.Current opinion in rheumatology · 2017Review
- Ro52 autoantibodies arise from self-reactive progenitors in a mother of a child with neonatal lupus.Journal of autoimmunity · 2017Article
- Endosomal Toll-like receptors in clinically overt and silent autoimmunity.Immunological reviews · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Based on the consistent demonstration of fibrosis of the atrioventricular node surrounded by macrophages and multinucleated giant cells in anti-Ro antibody exposed fetuses dying with heart block, this study focuses on macrophage signaling stimulated by ssRNA associated with the Ro60 protein and the impact of antagonizing innate cell drivers such as TLR7/8. Transcriptome and epigenetic modifications which affect transcription factors, NF-κB and STAT1, were selected to evaluate the phenotype of macrophages in which TLR7/8 was ligated following treatment with either anti-Ro60/Ro60/hY3 RNA immune complexes or transfection with hY3. Based on microarray, TNF and IL6 were among the most highly upregulated genes in both stimulated conditions, each of which was significantly inhibited by preincubation with hydroxychloroquine (HCQ). In contrast, following stimulation of macrophages with either TNF-α or IFN-α, which do not signal through TLR, the resultant gene expression was refractory to HCQ. Ligation of TLR7/8 resulted in increased histone methylation as measured by increased H3K4me2, a requirement for binding of NF-κB at certain promoters, specifically the kB1 region in the TNF promoter (ChIP-qPCR), which was significantly decreased by HCQ. In summary, these results support that the HCQ-sensitive phenotype of hY3 stimulated macrophages reflects the bifurcation of TLR downstream signals involving NF-κB and STAT 1 pathways and for the former dimethylation of H3K4. Accordingly, HCQ may act more as a preventive measure in downregulating the initial production of IFN-α or TNF-α and not affect the resultant autocoid stimulation reflected in TNF-α and IFN-α responsive genes. The beneficial scope of antimalarials in the prevention of organ damage, inclusive of heart block in an anti-Ro offspring or more broadly SLE, may include in part, a mechanism targeting TLR-dependent epigenetic modification.
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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.