ArticleBlood2017
Marginal zone B cells are critical to factor VIII inhibitor formation in mice with hemophilia A.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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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
52 citing papers in PubMed, 56 citations in OpenAlex.
- B cell-activating factor modulates the factor VIII immune response in hemophilia A.The Journal of clinical investigation · 2021Trial
- Trial
- Long-term impact of COVID-19 on haemophilia: a multicenter study in Southwest China.BMC infectious diseases · 2026Article
- The Immunology of Transfusion Medicine: Past, Present, and Future.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Mouse Model of Hemolytic Disease of the Fetus and Newborn.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Defining the Role of Marginal Zone B Cells in FVIII Inhibitor Development.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Analysis of Erythrocyte Membrane Alloantigens.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Acute Incompatible Red Blood Cell Transfusion in Mice.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Anemia and Transfusion in Preclinical Models of Neonatology.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Use of Microbial Microarrays to Define Antibody Specificity.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Expression and Characterization of Blood Group Binding Lectins.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Analysis of Galectin Binding to Blood Group Expressing Bacteria.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
- Murine Models of Transfusion-Induced Red Blood Cell Alloimmunization.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Analysis of Biotinylated Red Blood Cells Following Transfusion.Methods in molecular biology (Clifton, N.J.) · 2026Article
- The T follicular helper/T follicular helper regulatory pathway in FVIII immune responses in mice.Blood · 2025Article
- Complement is activated in patients with acute chest syndrome caused by sickle cell disease and represents a therapeutic target.Science translational medicine · 2025Article
- CD47 regulates antigen modulation and red blood cell clearance following an incompatible transfusion.Frontiers in immunology · 2025Article
- Review
- Harnessing the potential of red blood cells in immunotherapy.Human immunology · 2024Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Although factor VIII (FVIII) replacement therapy can be lifesaving for patients with hemophilia A, neutralizing alloantibodies to FVIII, known as inhibitors, develop in a significant number of patients and actively block FVIII activity, making bleeding difficult to control and prevent. Although a variety of downstream immune factors likely regulate inhibitor formation, the identification and subsequent targeting of key initiators in inhibitor development may provide an attractive approach to prevent inhibitor formation before amplification of the FVIII immune response occurs. As the initial steps in FVIII inhibitor development remain incompletely understood, we sought to define early regulators of FVIII inhibitor formation. Our results demonstrate that FVIII localizes in the marginal sinus of the spleen of FVIII-deficient mice shortly after injection, with significant colocalization with marginal zone (MZ) B cells. FVIII not only colocalizes with MZ B cells, but specific removal of MZ B cells also completely prevented inhibitor development following FVIII infusion. Subsequent rechallenge with FVIII following MZ B-cell reconstitution resulted in a primary antibody response, demonstrating that MZ B-cell depletion did not result in FVIII tolerance. Although recipient exposure to the viral-like adjuvant polyinosinic:polycytidylic acid enhanced anti-FVIII antibody formation, MZ B-cell depletion continued to display similar effectiveness in preventing inhibitor formation following FVIII infusion in this inflammatory setting. These data strongly suggest that MZ B cells play a critical role in initiating FVIII inhibitor formation and suggest a potential strategy to prevent anti-FVIII alloantibody formation in patients with hemophilia A.
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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.