Genetic risk factors for inhibitors in haemophilia A
(2015) In European Journal of Haematology 94. p.7-10- Abstract
- The current most serious side effect of haemophilia treatment is inhibitor development. Significant progress has been made over the last decades to understand why this complication occurs in some patients and it seems clear that both genetic and non-genetic factors are involved. Several issues however remain to be settled. A review was undertaken to summarise some key findings regarding the current view and available data on genetic markers of potential importance within this area. The causative F8 mutation, together with the HLA class II alleles, plays a pivotal pathophysiological role in inhibitor development. The types of mutation most frequently associated with inhibitors are large deletions, nonsense mutations, inversions, small... (More)
- The current most serious side effect of haemophilia treatment is inhibitor development. Significant progress has been made over the last decades to understand why this complication occurs in some patients and it seems clear that both genetic and non-genetic factors are involved. Several issues however remain to be settled. A review was undertaken to summarise some key findings regarding the current view and available data on genetic markers of potential importance within this area. The causative F8 mutation, together with the HLA class II alleles, plays a pivotal pathophysiological role in inhibitor development. The types of mutation most frequently associated with inhibitors are large deletions, nonsense mutations, inversions, small deletions/insertions without A-runs, splice-site mutations at conserved nucleotides and certain missense mutations. Regarding HLA class II allele, it has been hard to consistently identify risk alleles. Ethnicity has consistently been associated with inhibitor risk, but the causality of this has so far not been resolved. Among immune regulatory molecules, several polymorphic molecules have been suggested to be of importance. Most of these need additional studies and immune system challenges have to be fully evaluated. Inhibitor risk should be further defined, as patients in the future may be offered non-immunogenic treatments. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5075986
- author
- Bardi, Edit and Astermark, Jan LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- genetics, haemophilia, inhibitors, HLA, ethnicity, immune regulatory, molecules, mutation
- in
- European Journal of Haematology
- volume
- 94
- pages
- 7 - 10
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000347371100003
- scopus:84920267316
- pmid:25560788
- ISSN
- 1600-0609
- DOI
- 10.1111/ejh.12495
- language
- English
- LU publication?
- yes
- id
- 6642c3b8-275a-4065-b498-2f66f09b6737 (old id 5075986)
- date added to LUP
- 2016-04-01 10:17:36
- date last changed
- 2022-02-10 00:42:15
@article{6642c3b8-275a-4065-b498-2f66f09b6737,
abstract = {{The current most serious side effect of haemophilia treatment is inhibitor development. Significant progress has been made over the last decades to understand why this complication occurs in some patients and it seems clear that both genetic and non-genetic factors are involved. Several issues however remain to be settled. A review was undertaken to summarise some key findings regarding the current view and available data on genetic markers of potential importance within this area. The causative F8 mutation, together with the HLA class II alleles, plays a pivotal pathophysiological role in inhibitor development. The types of mutation most frequently associated with inhibitors are large deletions, nonsense mutations, inversions, small deletions/insertions without A-runs, splice-site mutations at conserved nucleotides and certain missense mutations. Regarding HLA class II allele, it has been hard to consistently identify risk alleles. Ethnicity has consistently been associated with inhibitor risk, but the causality of this has so far not been resolved. Among immune regulatory molecules, several polymorphic molecules have been suggested to be of importance. Most of these need additional studies and immune system challenges have to be fully evaluated. Inhibitor risk should be further defined, as patients in the future may be offered non-immunogenic treatments.}},
author = {{Bardi, Edit and Astermark, Jan}},
issn = {{1600-0609}},
keywords = {{genetics; haemophilia; inhibitors; HLA; ethnicity; immune regulatory; molecules; mutation}},
language = {{eng}},
pages = {{7--10}},
publisher = {{Wiley-Blackwell}},
series = {{European Journal of Haematology}},
title = {{Genetic risk factors for inhibitors in haemophilia A}},
url = {{http://dx.doi.org/10.1111/ejh.12495}},
doi = {{10.1111/ejh.12495}},
volume = {{94}},
year = {{2015}},
}