ArticleJournal of thrombosis and haemostasis : JTH2020
Combined anti-CD20 and mTOR inhibition with factor VIII for immune tolerance induction in hemophilia A patients with refractory inhibitors.
Article in Journal of thrombosis and haemostasis : JTH, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Pooled it
- B cell-activating factor modulates the factor VIII immune response in hemophilia A.The Journal of clinical investigation · 2021Trial
- Transplanted gene-modified placental cells boost FVIII activity in pediatric sheep without eliciting immunity, toxicity, or adverse events.Frontiers in immunology · 2025Article
- B cell focused transient immune suppression protocol for efficient AAV readministration to the liver.Molecular therapy. Methods & clinical development · 2024Article
- Oral tolerance to prevent anti-drug antibody formation in protein replacement therapies.Cellular immunology · 2022Review
- Article
- Hemophilia a patients with inhibitors: Mechanistic insights and novel therapeutic implications.Frontiers in immunology · 2022Review
- B Cell Depletion Eliminates FVIII Memory B Cells and Enhances AAV8-coF8 Immune Tolerance Induction When Combined With Rapamycin.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHemophilia A (HA) inhibitor patients that fail traditional immune tolerance induction (ITI) have increased morbidity and mortality. Preclinical studies support factor VIII (FVIII) tolerance induction with a combined approach of anti-CD20 mediated transient B cell depletion and rapamycin mediated regulatory T cell (Treg) induction.
methodsTwo refractory HA inhibitor patients were treated with rituximab, rapamycin, and FVIII ITI. Their clinical course, anti-FVIII immunoglobulins, cytokines, and select lymphocytes were followed.
resultsOne patient achieved complete and the other partial FVIII tolerance; both had marked annualized bleeding rate improvement. FVIII-specific immunoglobulins, but not total Treg counts, correlated with tolerance induction. IL-6 and IL-21 correlation with complete tolerance induction may support that down-regulation of T effectors and IgG4 production, respectively, contribute to the pathogenesis of tolerance induction.
conclusionsThis regimen may be considered to induce FVIII tolerance in HA patients with refractory inhibitors. Further characterization of the FVIII-specific immune response is necessary to clarify the mechanism of immune tolerance.
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