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Prevention and prediction of inhibitor risk.

Astermark, Jan LU (2012) In Haemophilia 18 Suppl 4. p.38-42
Abstract
Summary:

Studies of determinants of the development of inhibitory antibodies in patients with haemophilia indicate that this is a complex process involving several factors. The foundation is characterized by the T- and B-cell repertoire and the antigen presenting cells and to elicit an immune response to the deficient factor, a pre-disposing foundation is needed. Hence, in the absence of a certain set of circumstances, there will be no risk for development of inhibitors. Conversely, in patients fundamentally at risk, genetic and non-genetic factors might add to the risk. These factors may be additive or interactive, and ultimately promote or counteract the immune reaction by modifying immune regulators and the cytokine profile in... (More)
Summary:

Studies of determinants of the development of inhibitory antibodies in patients with haemophilia indicate that this is a complex process involving several factors. The foundation is characterized by the T- and B-cell repertoire and the antigen presenting cells and to elicit an immune response to the deficient factor, a pre-disposing foundation is needed. Hence, in the absence of a certain set of circumstances, there will be no risk for development of inhibitors. Conversely, in patients fundamentally at risk, genetic and non-genetic factors might add to the risk. These factors may be additive or interactive, and ultimately promote or counteract the immune reaction by modifying immune regulators and the cytokine profile in an individual. In some subjects, only minor inflammatory signals might be needed, whereas in others a more pronounced pro-inflammatory state will be required. Regarding genetic markers other than the type of mutation and the HLA class II molecules, polymorphisms in various immune regulatory genes have been associated with inhibitor risk. These associations have not, however, been consistent across all patient groups. The reason for this is not clear, but could be related to study design or statistical power, family relationships among those studied, the complexity of interacting molecules and ethnic genomic variation. The Hemophilia Inhibitor Genetics Study (HIGS) has identified additional candidates within the intracellular pathways, all of which require additional evaluation to be fully appreciated. In the case of non-genetic factors, the overall view is that immune system challenges might add to the risk. HIGS data suggest that it will be possible to calculate a genetic score to identify patients at high risk for inhibitor development before the start of treatment. By doing so, it may hopefully be possible in the future to prevent the formation of inhibitors in these patients by offering therapeutic options other than the native factor VIII or IX molecule in an inflammatory setting. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Haemophilia
volume
18 Suppl 4
pages
38 - 42
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000305605400007
  • pmid:22726081
  • scopus:84862883478
ISSN
1351-8216
DOI
10.1111/j.1365-2516.2012.02827.x
language
English
LU publication?
yes
id
c613bed5-cf18-4266-962c-524894a0c3f4 (old id 2858927)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22726081?dopt=Abstract
date added to LUP
2012-07-04 19:45:28
date last changed
2017-01-01 07:35:23
@article{c613bed5-cf18-4266-962c-524894a0c3f4,
  abstract     = {Summary:<br/><br>
Studies of determinants of the development of inhibitory antibodies in patients with haemophilia indicate that this is a complex process involving several factors. The foundation is characterized by the T- and B-cell repertoire and the antigen presenting cells and to elicit an immune response to the deficient factor, a pre-disposing foundation is needed. Hence, in the absence of a certain set of circumstances, there will be no risk for development of inhibitors. Conversely, in patients fundamentally at risk, genetic and non-genetic factors might add to the risk. These factors may be additive or interactive, and ultimately promote or counteract the immune reaction by modifying immune regulators and the cytokine profile in an individual. In some subjects, only minor inflammatory signals might be needed, whereas in others a more pronounced pro-inflammatory state will be required. Regarding genetic markers other than the type of mutation and the HLA class II molecules, polymorphisms in various immune regulatory genes have been associated with inhibitor risk. These associations have not, however, been consistent across all patient groups. The reason for this is not clear, but could be related to study design or statistical power, family relationships among those studied, the complexity of interacting molecules and ethnic genomic variation. The Hemophilia Inhibitor Genetics Study (HIGS) has identified additional candidates within the intracellular pathways, all of which require additional evaluation to be fully appreciated. In the case of non-genetic factors, the overall view is that immune system challenges might add to the risk. HIGS data suggest that it will be possible to calculate a genetic score to identify patients at high risk for inhibitor development before the start of treatment. By doing so, it may hopefully be possible in the future to prevent the formation of inhibitors in these patients by offering therapeutic options other than the native factor VIII or IX molecule in an inflammatory setting.},
  author       = {Astermark, Jan},
  issn         = {1351-8216},
  language     = {eng},
  pages        = {38--42},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Haemophilia},
  title        = {Prevention and prediction of inhibitor risk.},
  url          = {http://dx.doi.org/10.1111/j.1365-2516.2012.02827.x},
  volume       = {18 Suppl 4},
  year         = {2012},
}