ArticleHaematologica2016
Altered heme-mediated modulation of dendritic cell function in sickle cell alloimmunization.
Article in Haematologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 34 citations in OpenAlex.
- Acute Incompatible Red Blood Cell Transfusion in Mice.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Examination of Antigen-Specific B Cell Responses to Red Blood Cell Transfusion.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Analysis of Erythrocyte Membrane Alloantigens.Methods in molecular biology (Clifton, N.J.) · 2026Article
- The Immunology of Transfusion Medicine: Past, Present, and Future.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Anemia and Transfusion in Preclinical Models of Neonatology.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Determining the Binding Affinity in Monoclonal Antibody-Alloantigen Interactions.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Research progress in RBC alloimmunization.Frontiers in immunology · 2025Review
- Harnessing the potential of red blood cells in immunotherapy.Human immunology · 2024Review
- Dynamics of antibody engagement of red blood cellsFrontiers in immunology · 2024Article
- Article
- The Development and Consequences of Red Blood Cell Alloimmunization.Annual review of pathology · 2023Review
- An Analysis of the Multifaceted Roles of Heme in the Pathogenesis of Cancer and Related Diseases.Cancers · 2021Review
- Article
- Iron Overload in Patients With Heavily Transfused Sickle Cell Disease-Correlation of Serum Ferritin With Cardiac T2Frontiers in medicine · 2021Article
- Red blood cell alloimmunization and sickle cell disease: a narrative review on antibody induction.Annals of blood · 2020Article
- Article
- Innate immune cells, major protagonists of sickle cell disease pathophysiology.Haematologica · 2020Review
- Inflammatory Dendritic Cells Contribute to Regulate the Immune Response in Sickle Cell Disease.Frontiers in immunology · 2020Article
- Critical role of C5a in sickle cell disease.American journal of hematology · 2019Article
- How I safely transfuse patients with sickle-cell disease and manage delayed hemolytic transfusion reactions.Blood · 2018Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Transfusions are the main treatment for patients with sickle cell disease. However, alloimmunization remains a major life-threatening complication for these patients, but the mechanism underlying pathogenesis of alloimmunization is not known. Given the chronic hemolytic state characteristic of sickle cell disease, resulting in release of free heme and activation of inflammatory cascades, we tested the hypothesis that anti-inflammatory response to heme is compromised in alloimmunized sickle patients, increasing their risk of alloimmunization. Heme-exposed monocyte-derived dendritic cells from both non-alloimmunized sickle patients and healthy donors inhibited priming of pro-inflammatory CD4(+) type 1 T cells, and exhibited significantly reduced levels of the maturation marker CD83. In contrast, in alloimmunized patients, heme did not reverse priming of pro-inflammatory CD4(+) cells by monocyte-derived dendritic cells or their maturation. Furthermore, heme dampened NF-κB activation in non-alloimmunized, but not in alloimmunized monocyte-derived dendritic cells. Heme-mediated CD83 inhibition depended on Toll-like receptor 4 but not heme oxygenase 1. These data suggest that extracellular heme limits CD83 expression on dendritic cells in non-alloimmunized sickle patients through a Toll-like receptor 4-mediated pathway, involving NF-κB, resulting in dampening of pro-inflammatory responses, but that in alloimmunized patients this pathway is defective. This opens up the possibility of developing new therapeutic strategies to prevent sickle cell alloimmunization.
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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.