Trial reportThe Journal of clinical investigation2021
B cell-activating factor modulates the factor VIII immune response in hemophilia A.
Trial report in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Maternal microchimerism accelerates immune tolerance induction to factor VIII in children with hemophilia A and FVIII inhibitors.Frontiers in immunology · 2026Observational
- Large deletions in theResearch and practice in thrombosis and haemostasis · 2025Article
- Immune System-Related Genetic Risk Factors for Inhibitory Antibody Development in Patients With Hemophilia: Reviewing an Old Problem From a New Perspective-A Narrative Review.Health science reports · 2025Article
- Exploration of biomarkers for inhibitor development in persons with hemophilia A.Research and practice in thrombosis and haemostasis · 2025Article
- Acquired Hemophilia Associated with Rheumatoid Arthritis: A Case Report and Review of the Literature.International journal of molecular sciences · 2025Review
- CXCR5 engineered human and murine Tregs for targeted suppression in secondary and tertiary lymphoid organs.Frontiers in immunology · 2025Article
- Chemokine CXCL13 facilitates anti-FVIII inhibitory antibody development in hemophilia A patients and murine models.International immunopharmacology · 2024Article
- Review
- Biomarkers Involved in the Pathogenesis of Hemophilic Arthropathy.International journal of molecular sciences · 2024Review
- Abnormal frequency of the memory B cell subsets and plasmablasts in patients with congenital severe hemophilia A: correlation with "Inhibitor" formation.Blood research · 2024Article
- B cell focused transient immune suppression protocol for efficient AAV readministration to the liver.Molecular therapy. Methods & clinical development · 2024Article
- Article
- Can T-cell and B-cell excision circles predict development of inhibitors in pediatric hemophilia A?Pediatric research · 2023Article
- Immune tolerance against infused FVIII in hemophilia A is mediated by PD-L1+ Tregs.The Journal of clinical investigation · 2022Article
- Impact of different factor VIII inhibitor kinetic profiles on the inhibitor titer quantification using the modified Nijmegen-Bethesda assay.Research and practice in thrombosis and haemostasis · 2022Article
- Increased B Cell-Activating Factor Expression Is Associated with Postoperative Recurrence of Chronic Rhinosinusitis with Nasal Polyps.Mediators of inflammation · 2022Article
- Hemophilia a patients with inhibitors: Mechanistic insights and novel therapeutic implications.Frontiers in immunology · 2022Review
- Genomic Designs of rAAVs Contribute to Pathological Changes in the Livers and Spleens of Mice.Advances in cell and gene therapy · 2022Article
- A review of existing strategies for designing long-acting parenteral formulations: Focus on underlying mechanisms, and future perspectives.Acta pharmaceutica Sinica. B · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Inhibitors of factor VIII (FVIII) remain the most challenging complication of FVIII protein replacement therapy in hemophilia A (HA). Understanding the mechanisms that guide FVIII-specific B cell development could help identify therapeutic targets. The B cell-activating factor (BAFF) cytokine family is a key regulator of B cell differentiation in normal homeostasis and immune disorders. Thus, we used patient samples and mouse models to investigate the potential role of BAFF in modulating FVIII inhibitors. BAFF levels were elevated in pediatric and adult HA inhibitor patients and decreased to levels similar to those of noninhibitor controls after successful immune tolerance induction (ITI). Moreover, elevations in BAFF levels were seen in patients who failed to achieve FVIII tolerance with anti-CD20 antibody-mediated B cell depletion. In naive HA mice, prophylactic anti-BAFF antibody therapy prior to FVIII immunization prevented inhibitor formation and this tolerance was maintained despite FVIII exposure after immune reconstitution. In preimmunized HA mice, combination therapy with anti-CD20 and anti-BAFF antibodies dramatically reduced FVIII inhibitors via inhibition of FVIII-specific plasma cells. Our data suggest that BAFF may regulate the generation and maintenance of FVIII inhibitors and/or anti-FVIII B cells. Finally, anti-CD20/anti-BAFF combination therapy may be clinically useful for ITI.
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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.