ArticleThe Journal of clinical investigation2015
IDO1 suppresses inhibitor development in hemophilia A treated with factor VIII.
Article in The Journal of clinical investigation, 2015. 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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, 43 citations in OpenAlex.
- Large deletions in theResearch and practice in thrombosis and haemostasis · 2025Article
- A scan of pleiotropic immune mediated disease genes identifies novel determinants of baseline FVIII inhibitor status in hemophilia A.Genes and immunity · 2025Article
- Indoleamine 2,3-dioxygenase 1 is essential for sustaining durable antibody responses.Immunity · 2021Article
- Tolerance to FVIII: Role of the Immune Metabolic Enzymes Indoleamine 2,3 Dyoxigenase-1 and Heme Oxygenase-1.Frontiers in immunology · 2020Review
- Removal of Mannose-Ending Glycan at AsnFrontiers in immunology · 2020Article
- Molecular Mechanisms of Inhibitor Development in Hemophilia.Mediterranean journal of hematology and infectious diseases · 2020Review
- Pathogenic immune response to therapeutic factor VIII: exacerbated response or failed induction of tolerance?Haematologica · 2019Review
- Reversal of indoleamine 2,3-dioxygenase-mediated cancer immune suppression by systemic kynurenine depletion with a therapeutic enzyme.Nature biotechnology · 2018Article
- S1P promotes migration, differentiation and immune regulatory activity in amniotic-fluid-derived stem cells.European journal of pharmacology · 2018Article
- Review
- Tryptophan-Derived 3-Hydroxyanthranilic Acid Contributes to Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice In Vivo.Circulation · 2017Article
- Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases.Cellular and molecular life sciences : CMLS · 2017Review
- Co-delivery of indoleamine 2,3-dioxygenase prevents loss of expression of an antigenic transgene in dystrophic mouse muscles.Gene therapy · 2017Article
- Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A.Frontiers in immunology · 2017Review
- CpG Type A Induction of an Early Protective Environment in Experimental Multiple Sclerosis.Mediators of inflammation · 2017Article
- IDO1 and TGF-β Mediate Protective Effects of IFN-α in Antigen-Induced Arthritis.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance.Trends in immunology · 2016Review
- Article
- The proatherosclerotic function of indoleamine 2, 3-dioxygenase 1 in the developmental stage of atherosclerosis.Signal transduction and targeted therapyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors at 11 institutions in 5 countries.
Funding
Abstract
The development of inhibitory antibodies to factor VIII (FVIII) is a major obstacle in using this clotting factor to treat individuals with hemophilia A. Patients with a congenital absence of FVIII do not develop central tolerance to FVIII, and therefore, any control of their FVIII-reactive lymphocytes relies upon peripheral tolerance mechanisms. Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulatory enzyme that supports Treg function and peripheral tolerance in adult life. Here, we investigated the association between IDO1 competence and inhibitor status by evaluating hemophilia A patients harboring F8-null mutations that were either inhibitor negative (n = 50) or positive (n = 50). We analyzed IDO1 induction, expression, and function for any relationship with inhibitor occurrence by multivariable logistic regression and determined that defective TLR9-mediated activation of IDO1 induction is associated with an inhibitor-positive status. Evaluation of experimental hemophilic mouse models with or without functional IDO1 revealed that tryptophan metabolites, which result from IDO1 activity, prevent generation of anti-FVIII antibodies. Moreover, treatment of hemophilic animals with a TLR9 agonist suppressed FVIII-specific B cells by a mechanism that involves IDO1-dependent induction of Tregs. Together, these findings indicate that strategies aimed at improving IDO1 function should be further explored for preventing or eradicating inhibitors to therapeutically administered FVIII protein.
Indexed as
Identifiers
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.