Trial reportBlood2021
Circulating mitochondrial DNA is a proinflammatory DAMP in sickle cell disease.
Trial report in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 3 registered trials, which are not on this map. Cited by 89 papers.
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.
Human Specimen Collection to Support Basic and Clinical Research
Studies of the Natural History of Sickle Cell Disease
Pathophysiology of Acute Pain in Patients With Sickle Cell Disease
Who cites it
89 citing papers in PubMed, 116 citations in OpenAlex.
- Functional and multi-omics signatures of mitapivat efficacy upon activation of pyruvate kinase in red blood cells from patients with sickle cell disease.Haematologica · 2024Trial
- Mitochondrial Quality Control in Degenerative Musculoskeletal Diseases: Signaling Networks and Therapeutic Landscapes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mitochondrial genetic variation as a novel predictor of graft-versus-host disease after stem-cell transplantation in myelodysplastic neoplasms.Journal of hematology & oncology · 2026Article
- Variations in mitochondrial genome as potential prognostic markers in sickle cell disease.Haematologica · 2026Article
- Red blood cell metabolome maps disease burden, mutation class, and splenectomy status in hereditary spherocytosis.Blood red cells & iron · 2026Article
- Mitochondrial Damage in Hemoglobinopathies: The Role of Cell-Free mtDNA as a Potential Biomarker.Biomedicines · 2026Article
- DAMPs, PAMPs, and Alarmins: From Mechanism to Therapy.MedComm · 2026Review
- Beyond Pain: A Pilot Study of Neurodegenerative and Mitochondrial Pathway Alterations in Sickle Cell Disease Using Platelet Proteomics.Medical sciences (Basel, Switzerland) · 2026Article
- Plasma circulating free DNA in chronic schizophrenia: a case-control study.Scientific reports · 2026Article
- Article
- Surmounting Recalcitrant Airway Inflammatory Disorders With a Multi-Targeting Therapeutic Strategy by Tannic Acid-Modified CuInPExploration (Beijing, China) · 2026Article
- Extracellular heme:DNA complexes promote oxidative stress and inflammation during lupus-associated hemolysis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Pyruvate kinase deficiency modifies sickle hemoglobin carrier and sickle cell disease phenotypes in mice.JCI insight · 2026Article
- A novel transdermal curcumin gel shows potential in improving cardiac bioenergetic functions in Berkeley sickle cell mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Review
- Mitochondrial retention and autophagy dysregulation drive oxidative stress in sickle cell disease erythrocytes.Experimental hematology · 2025Article
- [Correlation analysis of cell-free DNA in gingival crevicular fluid with periodontal clinical indicators and cyclic guanosine phosphate-adenosine phosphate synthase-stimulator of interferon genes signaling pathway].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2025Article
- Electron microscopy visualization of cell-free mitochondrial DNA-containing extracellular vesicles in human plasma, serum, and saliva.medRxiv : the preprint server for health sciences · 2025Article
- Revealing Cell-Free Mitochondrial DNA Breakage Patterns as Novel Biomarkers for Sepsis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Disulfiram as an anti-inflammatory agent: mechanisms, nano-delivery strategies, and applications in non-oncologic diseases.RSC advances · 2025Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
22 authors at 2 institutions in 1 country.
Funding
Abstract
The pathophysiology of sickle cell disease (SCD) is driven by chronic inflammation fueled by damage associated molecular patterns (DAMPs). We show that elevated cell-free DNA (cfDNA) in patients with SCD is not just a prognostic biomarker, it also contributes to the pathological inflammation. Within the elevated cfDNA, patients with SCD had a significantly higher ratio of cell-free mitochondrial DNA (cf-mtDNA)/cell-free nuclear DNA compared with healthy controls. Additionally, mitochondrial DNA in patient samples showed significantly disproportionately increased hypomethylation compared with healthy controls, and it was increased further in crises compared with steady-state. Using flow cytometry, structured illumination microscopy, and electron microscopy, we showed that circulating SCD red blood cells abnormally retained their mitochondria and, thus, are likely to be the source of the elevated cf-mtDNA in patients with SCD. Patient plasma containing high levels of cf-mtDNA triggered the formation of neutrophil extracellular traps (NETs) that was substantially reduced by inhibition of TANK-binding kinase 1, implicating activation of the cGAS-STING pathway. cf-mtDNA is an erythrocytic DAMP, highlighting an underappreciated role for mitochondria in sickle pathology. These trials were registered at www.clinicaltrials.gov as #NCT00081523, #NCT03049475, and #NCT00047996.
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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.