ArticlePloS one2019
Risk stratification integrating genetic data for factor VIII inhibitor development in patients with severe hemophilia A.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation-Updated Consensus and Review 2020.Frontiers in immunology · 2020Pooled it
- TNF‑α Gene Polymorphisms as Determinants of Alloantibody Emergence in Hemophilia: A Systematic Review and Meta-Analysis.Haemophilia : the official journal of the World Federation of HemophiliaPooled it
- Simoctocog Alfa (Nuwiq) in Previously Untreated Patients with Severe Haemophilia A: Final Results of the NuProtect Study.Thrombosis and haemostasis · 2021Trial
- Shaping hemophilia care: lessons and legacy of the SIPPET trial after 10 years.Research and practice in thrombosis and haemostasis · 2026Review
- Large deletions in theResearch and practice in thrombosis and haemostasis · 2025Article
- Predicting inhibitor development using a random peptide phage-display library approach in the SIPPET cohort.Blood advances · 2024Article
- Genetic variants at the chromosomal region 2q21.3 underlying inhibitor development in patients with severe haemophilia A.Haemophilia : the official journal of the World Federation of Hemophilia · 2022Article
- Genome-Wide Association Study and Gene-Based Analysis of Participants With Hemophilia A and Inhibitors in the My Life, Our Future Research Repository.Frontiers in medicine · 2022Article
- Performance of a clinical risk prediction model for inhibitor formation in severe haemophilia A.Haemophilia : the official journal of the World Federation of Hemophilia · 2021Article
- Article
- HLA Variants and Inhibitor Development in Hemophilia A: A Retrospective Case-Controlled Study Using the ATHNdataset.Frontiers in medicine · 2021Article
- Factors Involved in the Development of Inhibitory Antibodies in Patients with Hemophilia in Colombia: A Case-Control Study.Clinical medicine insights. Blood disorders · 2020Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replacement therapy in severe hemophilia A leads to factor VIII (FVIII) inhibitors in 30% of patients. Factor VIII gene (F8) mutation type, a family history of inhibitors, ethnicity and intensity of treatment are established risk factors, and were included in two published prediction tools based on regression models. Recently investigated immune regulatory genes could also play a part in immunogenicity. Our objective is to identify bio-clinical and genetic markers for FVIII inhibitor development, taking into account potential genetic high order interactions. The study population consisted of 593 and 79 patients with hemophilia A from centers in Bonn and Frankfurt respectively. Data was collected in the European ABIRISK tranSMART database. A subset of 125 severely affected patients from Bonn with reliable information on first treatment was selected as eligible for risk stratification using a hybrid tree-based regression model (GPLTR). In the eligible subset, 58 (46%) patients developed FVIII inhibitors. Among them, 49 (84%) were "high risk" F8 mutation type. 19 (33%) had a family history of inhibitors. The GPLTR model, taking into account F8 mutation risk, family history of inhibitors and product type, distinguishes two groups of patients: a high-risk group for immunogenicity, including patients with positive HLA-DRB1*15 and genotype G/A and A/A for IL-10 rs1800896, and a low-risk group of patients with negative HLA-DRB1*15 / HLA-DQB1*02 and T/T or G/T for CD86 rs2681401. We show associations between genetic factors and the occurrence of FVIII inhibitor development in severe hemophilia A patients taking into account for high-order interactions using a generalized partially linear tree-based approach.
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