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Genetic risk factors for inhibitors in haemophilia A

Bardi, Edit and Astermark, Jan LU (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)
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author
organization
publishing date
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
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
2015-02-28 09:00:38
date last changed
2017-10-01 03:11:59
@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},
  keyword      = {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},
  volume       = {94},
  year         = {2015},
}