ArticleRheumatology (Oxford, England)2023
Reduced digestion of circulating genomic DNA in systemic sclerosis patients with the DNASE1L3 R206C variant.
Article in Rheumatology (Oxford, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.
- Pulmonary arterial hypertension susceptibility and mortality among patients with systemic sclerosis with the DNASE1L3 rs35677470 (Arg206Cys) variant.Annals of the rheumatic diseases · 2026Pooled it
- DNASE1L3 functions as a significant metastatic suppressor by attenuating MYH9/β-catenin/c-Jun/LncRNA-KDM4A-induced E-cadherin ubiquitination degradation in nasopharyngeal carcinoma.Cellular & molecular biology letters · 2026Article
- Nucleic acid triggers of autoimmunity and autoinflammation.Current opinion in immunology · 2025Review
- DNASE1L3-mediated PANoptosis enhances the efficacy of combination therapy for advanced hepatocellular carcinoma.Theranostics · 2024Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesPolymorphism in a coding region of deoxyribonuclease I-like III (DNASE1L3), causing amino acid substitution of Arg-206 to Cys (R206C), is a robustly replicated heritable risk factor for SSc and other autoimmune diseases. DNASE1L3 is secreted into the circulation, where it can digest genomic DNA (gDNA) in apoptosis-derived membrane vesicles (AdMVs). We sought to determine the impact of DNASE1L3 R206C on digestion of circulating gDNA in SSc patients and healthy controls (HCs).
methodsThe ability of DNASE1L3 to digest AdMV-associated gDNA was tested in vitro. The effect of R206C substitution on extracellular secretion of DNASE1L3 was determined using a transfected cell line and primary monocyte-derived dendritic cells from SSc patients. Plasma samples from SSc patients and HCs with DNASE1L3 R206C or R206 wild type were compared for their ability to digest AdMV-associated gDNA. The digestion status of endogenous gDNA in plasma samples from 123 SSc patients and 74 HCs was determined by measuring the proportion of relatively long to short gDNA fragments.
resultsThe unique ability of DNASE1L3 to digest AdMV-associated gDNA was confirmed. Extracellular secretion of DNASE1L3 R206C was impaired. Plasma from individuals with DNASE1L3 R206C had reduced ability to digest AdMV-associated gDNA. The ratio of long: short gDNA fragments was increased in plasma from SSc patients with DNASE1L3 R206C, and this ratio correlated inversely with DNase activity.
conclusionOur results confirm that circulating gDNA is a physiological DNASE1L3 substrate and show that its digestion is reduced in SSc patients with the DNASE1L3 R206C variant.
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Registered trials
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