دورية أكاديمية
أعرض في EDS

Risk stratification integrating genetic data for factor VIII inhibitor development in patients with severe hemophilia A.

التفاصيل البيبلوغرافية
العنوان: Risk stratification integrating genetic data for factor VIII inhibitor development in patients with severe hemophilia A.
المؤلفون: Delphine Bachelet, Thilo Albert, Cyprien Mbogning, Signe Hässler, Yuan Zhang, Stephan Schultze-Strasser, Yohann Repessé, Julie Rayes, Anna Pavlova, Behnaz Pezeshkpoor, Kerstin Liphardt, Julie E Davidson, Agnès Hincelin-Méry, Pierre Dönnes, Sébastien Lacroix-Desmazes, Christoph Königs, Johannes Oldenburg, Philippe Broët, ABIRISK consortium
المصدر: PLoS ONE, Vol 14, Iss 6, p e0218258 (2019)
بيانات النشر: Public Library of Science (PLoS), 2019.
سنة النشر: 2019
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0218258
URL الوصول: https://doaj.org/article/e167617cea974ae693edaf5a173d15e0
رقم الأكسشن: edsdoj.167617cea974ae693edaf5a173d15e0
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0218258