Trial reportCirculation research2015
Iron, inflammation, and early death in adults with sickle cell disease.
Open access · bronzeAbstract readClinical Trial
In one paragraph
Trial report in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 3 pooled it
4.5field-weighted citation impact, top 5% of its field
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
53 citing papers in PubMed, 3 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- Role of Serum Ferritin in Predicting Outcomes of COVID-19 Infection Among Sickle Cell Disease Patients: A Systematic Review and Meta-Analysis.Frontiers in medicine · 2022Pooled it
- Pooled it
- Role of innate immunity-triggered pathways in the pathogenesis of Sickle Cell Disease: a meta-analysis of gene expression studies.Scientific reports · 2015Pooled it
- Deferiprone for transfusional iron overload in sickle cell disease and other anemias: open-label study of up to 3 years.Blood advances · 2023Trial
- Estimated glomerular filtration rate discordance and cardiopulmonary morbidity in sickle cell disease.Blood advances · 2026Article
- Sickle cell disease-associated pulmonary hypertension: an integrated framework linking pathologies, mechanisms, and clinical phenotypes.EBioMedicine · 2026Review
- The role of interleukin-1 beta as an early biomarker for renal dysfunction in Egyptian sickle cell disease patients.Annals of hematology · 2026Article
- Can pre-transplant sickle cell disease characteristics predict early post-transplant complications?Bone marrow transplantation · 2026Article
- Interleukin-6 in hemolytic anemias: from inflammatory pathways to therapeutic targeting.Frontiers in immunology · 2026Review
- Advances in plant-derived vesicle like nanoparticles-based therapies for inflammatory diseases.Asian journal of pharmaceutical sciences · 2025Review
- Small Molecule Regulation of Iron Homeostasis: Design and Optimization of Novel Iron Chelators Based on a Thiosemicarbazone Scaffold.Journal of molecular structure · 2025Article
- Comparative Proteomic Analysis Reveals Altered Ciliary Proteins in Sickle Cell Disease.Journal of proteome research · 2025Article
- Crosstalk Between Sickle Cell Disease and Ferroptosis.International journal of molecular sciences · 2025Review
- Transcriptomic atlas reveals organ-specific disease tolerance in sickle cell mice.Blood advances · 2025Article
- Whole Blood Transcriptome Analysis in Congenital Anemia Patients.International journal of molecular sciences · 2024Article
- GBT1118, a Voxelotor Analog, Ameliorates Hepatopathy in Sickle Cell Disease.Medicina (Kaunas, Lithuania) · 2024Article
- Ferroptosis as an emerging target in sickle cell disease.Current research in toxicology · 2024Article
- Potential inflammatory targets in the integrative health care of patients with sickle cell disease.Experimental and therapeutic medicine · 2023Article
- Variation and impact of polygenic hematologic traits in monogenic sickle cell disease.Haematologica · 2023Article
- The NLRP3 inflammasome fires up heme-induced inflammation in hemolytic conditions.Translational research : the journal of laboratory and clinical medicine · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Eduard J van BeersFrom the Hematology Branch (E.J.v.B., D.T.A., J.S.N., L.M., J.G.T., G.J.K.), Genomics Core Facility (Y.Y., N.R.), and Office of Biostatistics Research (X.T.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC (S.N.); Comprehensive Sickle Cell Center, Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago (V.R.G.); and Division of Hematology-Oncology, Department of Medicine and the Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (G.J.K.). Current address: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands (E.J.v.B.).
Yanqin YangFrom the Hematology Branch (E.J.v.B., D.T.A., J.S.N., L.M., J.G.T., G.J.K.), Genomics Core Facility (Y.Y., N.R.), and Office of Biostatistics Research (X.T.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC (S.N.); Comprehensive Sickle Cell Center, Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago (V.R.G.); and Division of Hematology-Oncology, Department of Medicine and the Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (G.J.K.). Current address: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands (E.J.v.B.).
Nalini RaghavachariFrom the Hematology Branch (E.J.v.B., D.T.A., J.S.N., L.M., J.G.T., G.J.K.), Genomics Core Facility (Y.Y., N.R.), and Office of Biostatistics Research (X.T.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC (S.N.); Comprehensive Sickle Cell Center, Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago (V.R.G.); and Division of Hematology-Oncology, Department of Medicine and the Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (G.J.K.). Current address: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands (E.J.v.B.).
Xin TianFrom the Hematology Branch (E.J.v.B., D.T.A., J.S.N., L.M., J.G.T., G.J.K.), Genomics Core Facility (Y.Y., N.R.), and Office of Biostatistics Research (X.T.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC (S.N.); Comprehensive Sickle Cell Center, Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago (V.R.G.); and Division of Hematology-Oncology, Department of Medicine and the Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (G.J.K.). Current address: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands (E.J.v.B.).
Darlene T AllenFrom the Hematology Branch (E.J.v.B., D.T.A., J.S.N., L.M., J.G.T., G.J.K.), Genomics Core Facility (Y.Y., N.R.), and Office of Biostatistics Research (X.T.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC (S.N.); Comprehensive Sickle Cell Center, Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago (V.R.G.); and Division of Hematology-Oncology, Department of Medicine and the Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (G.J.K.). Current address: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands (E.J.v.B.).
James S NicholsFrom the Hematology Branch (E.J.v.B., D.T.A., J.S.N., L.M., J.G.T., G.J.K.), Genomics Core Facility (Y.Y., N.R.), and Office of Biostatistics Research (X.T.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC (S.N.); Comprehensive Sickle Cell Center, Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago (V.R.G.); and Division of Hematology-Oncology, Department of Medicine and the Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (G.J.K.). Current address: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands (E.J.v.B.).
Laurel MendelsohnFrom the Hematology Branch (E.J.v.B., D.T.A., J.S.N., L.M., J.G.T., G.J.K.), Genomics Core Facility (Y.Y., N.R.), and Office of Biostatistics Research (X.T.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC (S.N.); Comprehensive Sickle Cell Center, Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago (V.R.G.); and Division of Hematology-Oncology, Department of Medicine and the Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (G.J.K.). Current address: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands (E.J.v.B.).
Sergei NekhaiFrom the Hematology Branch (E.J.v.B., D.T.A., J.S.N., L.M., J.G.T., G.J.K.), Genomics Core Facility (Y.Y., N.R.), and Office of Biostatistics Research (X.T.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC (S.N.); Comprehensive Sickle Cell Center, Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago (V.R.G.); and Division of Hematology-Oncology, Department of Medicine and the Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (G.J.K.). Current address: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands (E.J.v.B.).
Victor R GordeukFrom the Hematology Branch (E.J.v.B., D.T.A., J.S.N., L.M., J.G.T., G.J.K.), Genomics Core Facility (Y.Y., N.R.), and Office of Biostatistics Research (X.T.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC (S.N.); Comprehensive Sickle Cell Center, Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago (V.R.G.); and Division of Hematology-Oncology, Department of Medicine and the Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (G.J.K.). Current address: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands (E.J.v.B.).
James G TaylorFrom the Hematology Branch (E.J.v.B., D.T.A., J.S.N., L.M., J.G.T., G.J.K.), Genomics Core Facility (Y.Y., N.R.), and Office of Biostatistics Research (X.T.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC (S.N.); Comprehensive Sickle Cell Center, Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago (V.R.G.); and Division of Hematology-Oncology, Department of Medicine and the Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (G.J.K.). Current address: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands (E.J.v.B.).
Gregory J KatoFrom the Hematology Branch (E.J.v.B., D.T.A., J.S.N., L.M., J.G.T., G.J.K.), Genomics Core Facility (Y.Y., N.R.), and Office of Biostatistics Research (X.T.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington, DC (S.N.); Comprehensive Sickle Cell Center, Section of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago (V.R.G.); and Division of Hematology-Oncology, Department of Medicine and the Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (G.J.K.). Current address: Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands (E.J.v.B.). katogj@upmc.edu.
University of Illinois Chicago · USHoward University · US
Funding
DNA Sequencing Core (DSC)ZICHL006058 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI ZHU, JUN · 2010 to 2016
$16.6MPROTEOMICS CORE FACILITYG12MD007597 · NIMHD · HOWARD UNIVERSITY · PI SOUTHERLAND, WILLIAM M. · 2012 to 2018
$14.8MCenter for Hemoglobin Research in Minorities (CHaRM)P50HL118006 · NHLBI · HOWARD UNIVERSITY · PI NEKHAI, SERGEI · 2013 to 2017
$7.0MSickle Cell Disease and Sickle Cell Trait Protection Against HIV-1-infection in Africans and African AmericansR01HL125005 · NHLBI · HOWARD UNIVERSITY · PI MARINA A JEREBTSOVA, SERGEI NEKHAI · 2014 to 2026
$6.7MGenomic Determinants of Phenotypes of Sickle Cell DiseaseZIAHL006160 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI TAYLOR, JAMES · 2012 to 2016
$5.1MPrevalence and Prognosis of Pulmonary Hypertension in Adults with Sickle CellZIAHL006012 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI TAYLOR, JAMES · 2009 to 2016
$3.5MBlood Studies of Endothelial Function and Systemic InflammationZIAHL006013 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI KATO, GREGORY · 2009 to 2013
$680kPlasma Biomarkers of Sickle Cell Pulmonary HypertensionZIAHL006162 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI KATO, GREGORY · 2012 to 2013
$506kAtorvastatin Therapy to Improve Endothelial Function in Sickle Cell DiseaseZIAHL006023 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI KATO, GREGORY · 2009 to 2013
$258kIntramural NIH HHS ZIA HL006012Intramural NIH HHS ZIA HL006013Intramural NIH HHS ZIA HL006023Intramural NIH HHS ZIA HL006162NHLBI NIH HHS 1ZIA HL006013-03NHLBI NIH HHS 1 ZIA HL006023-03NHLBI NIH HHS P50 HL118006NHLBI NIH HHS R01 HL125005NIMHD NIH HHS G12 MD007597PHS HHS 1ZIAHL006012-02
Abstract
rationalePatients with sickle cell disease (SCD) have markers of chronic inflammation, but the mechanism of inflammation and its relevance to patient survival are unknown.
objectiveTo assess the relationship between iron, inflammation, and early death in SCD. METHODS AND
resultsUsing peripheral blood mononuclear cell transcriptome profile hierarchical clustering, we classified 24 patients and 10 controls in clusters with significantly different expression of genes known to be regulated by iron. Subsequent gene set enrichment analysis showed that many genes associated with the high iron cluster were involved in the toll-like receptor system (TLR4, TLR7, and TLR8) and inflammasome complex pathway (NLRP3, NLRC4, and CASP1). Quantitative PCR confirmed this classification and showed that ferritin light chain, TLR4, and interleukin-6 expression were >100-fold higher in patients than in controls (P<0.001). Further linking intracellular iron and inflammation, 14 SCD patients with a ferroportin Q248H variant that causes intracellular iron accumulation had significantly higher levels of interleukin-6 and C-reactive protein compared with 14 matched SCD patients with the wild-type allele (P<0.05). Finally, in a cohort of 412 patients followed for a median period of 47 months (interquartile range, 24-82), C-reactive protein was strongly and independently associated with early death (hazard ratio, 3.0; 95% confidence interval, 1.7-5.2; P<0.001).
conclusionsGene expression markers of high intracellular iron in patients with SCD are associated with markers of inflammation and mortality. The results support a model in which intracellular iron promotes inflammatory pathways, such as the TLR system and the inflammasome, identifying important new pathways for additional investigation.
Indexed as
AdultAnemia, Sickle CellCohort StudiesFemaleGenetic MarkersHumansInflammationIronLeukocytes, MononuclearMaleMortalityProspective StudiesRegistriesGenetic MarkersIrongene expressioninflammationironmortalitysickle cell disease
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.