ArticleBlood2021
Hemolysis inhibits humoral B-cell responses and modulates alloimmunization risk in patients with sickle cell disease.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Antibody-Dependent and Antibody-Independent Hemolysis in Sickle Cell Disease.Antibodies (Basel, Switzerland) · 2026Review
- Adaptive Immune Remodeling in Sickle Cell Disease: Linking Hemolysis-Driven Inflammation to Immune Dysfunction.Experimental hematology · 2026Review
- Targeting erythroid cell-derived asparagine inhibits alloimmunization in sickle cell disease.Blood advances · 2026Article
- Unravelling the Immunological Enigma of Sickle Cell Disease: Current Understanding and Future Directions.Immunology · 2026Review
- DOCK8 in immune cells: roles and mechanisms.Frontiers in immunology · 2026Review
- The Immunology of Transfusion Medicine: Past, Present, and Future.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Determining the Binding Affinity in Monoclonal Antibody-Alloantigen Interactions.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Anemia and Transfusion in Preclinical Models of Neonatology.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Analysis of Erythrocyte Membrane Alloantigens.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
- Proinflammatory state promotes red blood cell alloimmunization in pediatric patients with sickle cell disease.Blood advances · 2023Article
- A Review of the Relationship between the Immune Response, Inflammation, Oxidative Stress, and the Pathogenesis of Sickle Cell Anaemia.Biomedicines · 2023Review
- Hemin treatment drives viral reactivation and plasma cell differentiation of EBV latently infected B cells.PLoS pathogens · 2023Article
- Article
- DOCK8 interference alleviates Aβ‑induced damage of BV2 cells by inhibiting STAT3/NLRP3/NF‑κB signaling.Experimental and therapeutic medicine · 2023Article
- The Development and Consequences of Red Blood Cell Alloimmunization.Annual review of pathology · 2023Review
- Impact of Hemin on Interleukin-21 Levels and Plasma Cells in Transfusion-Dependent Thalassemia with Positive and Negative Allo-Autoantibody.International journal of general medicine · 2023Article
- How to avoid the problem of erythrocyte alloimmunization in sickle cell disease.Hematology. American Society of Hematology. Education Program · 2021Review
- Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Red blood cell alloimmunization remains a barrier for safe and effective transfusions in sickle cell disease (SCD), but the associated risk factors remain largely unknown. Intravascular hemolysis, a hallmark of SCD, results in the release of heme with potent immunomodulatory activity, although its effect on SCD humoral response, specifically alloimmunization, remains unclear. Here, we found that cell-free heme suppresses human B-cell plasmablast and plasma cell differentiation by inhibiting the DOCK8/STAT3 signaling pathway, which is critical for B-cell activation, as well as by upregulating heme oxygenase 1 (HO-1) through its enzymatic byproducts, carbon monoxide and biliverdin. Whereas nonalloimmunized SCD B cells were inhibited by exogenous heme, B cells from the alloimmunized group were nonresponsive to heme inhibition and readily differentiated into plasma cells. Consistent with a differential B-cell response to hemolysis, we found elevated B-cell basal levels of DOCK8 and higher HO-1-mediated inhibition of activated B cells in nonalloimmunized compared with alloimmunized SCD patients. To overcome the alloimmunized B-cell heme insensitivity, we screened several heme-binding molecules and identified quinine as a potent inhibitor of B-cell activity, reversing the resistance to heme suppression in alloimmunized patients. B-cell inhibition by quinine occurred only in the presence of heme and through HO-1 induction. Altogether, these data suggest that hemolysis can dampen the humoral B-cell response and that B-cell heme responsiveness maybe a determinant of alloimmunization risk in SCD. By restoring B-cell heme sensitivity, quinine may have therapeutic potential to prevent and inhibit alloimmunization in SCD patients.
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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 Socratic graph.