ArticleBlood2015
Factor VIII gene variants and inhibitor risk in African American hemophilia A patients.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 55 citations in OpenAlex.
- Trial
- Race, Ethnicity, and Hemophilia: A Scoping Review.Journal of racial and ethnic health disparities · 2026Review
- A scan of pleiotropic immune mediated disease genes identifies novel determinants of baseline FVIII inhibitor status in hemophilia A.Genes and immunity · 2025Article
- Genomic Landscape of Chromosome X Factor VIII: From Hemophilia A in Males to Risk Variants in Females.Genes · 2024Article
- Prediction of the chance of successful immune tolerance induction in persons with severe hemophilia A and inhibitors: a clinical prediction model.Research and practice in thrombosis and haemostasis · 2024Article
- Anti-FVIII antibodies in Black and White hemophilia A subjects: do F8 haplotypes play a role?Blood advances · 2023Article
- Hemophilia A subjects with an intron-22 gene inversion mutation show CD4Frontiers in immunology · 2023Article
- Inhibitor; An Uncommon But Vexing Challenge In North Indian Patients With Hemophilia A.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2022Article
- Mechanistic Insights into Factor VIII Immune Tolerance Induction via Prenatal Cell Therapy in Hemophilia A.Current stem cell reports · 2019Article
- Complexity of immune responses to AAV transgene products - Example of factor IX.Cellular immunology · 2019Review
- Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy.Molecular therapy. Methods & clinical development · 2019Review
- Tolerating Factor VIII: Recent Progress.Frontiers in immunology · 2019Review
- Factor VIII: Perspectives on Immunogenicity and Tolerogenic Strategies.Frontiers in immunology · 2019Review
- An Observational Study from Long-Term AAV Re-administration in Two Hemophilia Dogs.Molecular therapy. Methods & clinical development · 2018Article
- FVIII proteins with a modified immunodominant T-cell epitope exhibit reduced immunogenicity and normal FVIII activity.Blood advances · 2018Article
- Many factor VIII products available in the treatment of hemophilia A: an embarrassment of riches?Journal of blood medicine · 2017Review
- Accurate, simple, and inexpensive assays to diagnoseBlood advances · 2016Article
- Engineering less immunogenic and antigenic FVIII proteins.Cellular immunology · 2016Review
- Severe Hemophilia A in a Male Old English Sheep Dog with a C→T Transition that Created a Premature Stop Codon in Factor VIII.Comparative medicine · 2016Article
- Complexity and diversity of F8 genetic variations in the 1000 genomes.Journal of thrombosis and haemostasis : JTH · 2015Article
Corrections and comments
- Commented on by
Authors and funding
12 authors at 7 institutions in 1 country.
Funding
Abstract
African American hemophilia A (HA) patients experience a higher incidence of neutralizing anti-factor VIII (FVIII) antibodies ("inhibitors") vis-à-vis white patients. Nonsynonymous single-nucleotide polymorphisms (ns-SNPs) in the F8 gene encoding FVIII-H484, FVIII-E1241, and FVIII-V2238 are more prevalent in African Americans. This study tested the hypothesis that immune responses to these sites provoke inhibitors. Blood samples were obtained from 174 African American and 198 white HA subjects and their F8 gene sequences determined. Major histocompatibility complex class II binding and T-cell recognition of polymorphic sequences were evaluated using quantitative binding assays and HLA-DRB1 tetramers. Peptides corresponding to 4 common ns-SNPs showed limited binding to 11 HLA-DRB1 proteins. CD4 T cells from 22 subjects treated with FVIII products having sequences at residues FVIII-484, 1241, and 2238 differing from those of putative proteins encoded by their F8 genes did not show high-avidity tetramer binding, whereas positive-control staining of tetanus-specific CD4 T cells was routinely successful. African Americans with an intron-22 inversion mutation showed a 2-3 times-higher inhibitor incidence than whites with the same mutation (odds ratio = 2.3 [1.1-5.0, P = .04]), but this did not correlate with any of the ns-SNPs. We conclude that immune responses to "sequence-mismatched" FVIII products are unlikely to contribute appreciably to the inhibitor incidence in African Americans.
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.