Inhibitor development in correlation to factor VIII genotypes

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dc.contributor.author El Maarri, O.
dc.contributor.author Oldenburg, J.
dc.contributor.author Schwaab, R.
dc.date.accessioned 2017-09-15T09:06:29Z
dc.date.available 2017-09-15T09:06:29Z
dc.date.copyright 2002 en_US
dc.identifier.issn 1365-2516 en_US
dc.identifier.uri http://hdl.handle.net/10725/6202
dc.description.abstract Alloantibodies (inhibitors) against factor VIII (FVIII) develop in 20–30% of patients with severe haemophilia A and render classical FVIII substitution therapy ineffective. Several studies have shown that genetic factors, the type of FVIII gene mutation and immune response genes (e.g. the Major Histocompatibility Complexes), influence the risk of inhibitor formation. In particular, the type of FVIII gene mutation has proven to be a decisive risk factor. Patients with severe molecular gene defects (e.g. large deletions, nonsense mutations, intron-22 inversion) and no endogenous FVIII synthesis have a 7–10 times higher inhibitor prevalence than patients with milder molecular gene defects (e.g. missense mutations, small deletions, splice site mutations). To date, at least 10 distinct classes of mutations have been shown which have differing risks of associated inhibitor formation. A challenging observation in inhibitor patients is the heterogeneity of the antibody epitopes with respect to their number and their specifity. At least five epitopes in the FVIII molecule have been identified that constitute the targets for antibodies in most inhibitor patients. These epitopes are located in the ar3 region and the A2, A3, C1, C2 domains which correspond to the functional binding sites of the ligands of the FVIII protein. At present, the determinants of the characteristics of these epitopes and the subsequent inhibitor titre are unknown. A relationship of the mutation site and the epitope localization has been shown for some individual patients with mild haemophilia A. However, in severely affected haemophilia A patients, the influence of patient genetics on inhibitor titre and epitope specifity has yet to be elucidated. en_US
dc.language.iso en en_US
dc.title Inhibitor development in correlation to factor VIII genotypes en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 201508713 en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.relation.journal Haemophilia en_US
dc.journal.volume 8 en_US
dc.journal.issue 2 en_US
dc.article.pages 23-29 en_US
dc.identifier.doi http://dx.doi.org/10.1046/j.1351-8216.2001.00134.x en_US
dc.identifier.ctation Oldenburg, J., El‐Maarri, O., & Schwaab, R. (2002). Inhibitor development in correlation to factor VIII genotypes. Haemophilia, 8(s2), 23-29. en_US
dc.author.email osman.elmaarri@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url http://onlinelibrary.wiley.com/doi/10.1046/j.1351-8216.2001.00134.x/full en_US
dc.author.affiliation Lebanese American University en_US

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