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The Malmo International Brother Study (MIBS): further support for genetic predisposition to inhibitor development in hemophilia patients

Astermark, Jan LU ; Berntorp, Erik LU ; White, G C and Kroner, B L (2001) In Haemophilia 7(3). p.267-272
Abstract
The issue of factors predisposing for inhibitor development in haemophilia patients is still largely unresolved. In an attempt to address this problem, we initiated a registry in 1996 of siblings with haemophilia and with or without a history of inhibitors. Four hundred and sixty families have accrued, of whom 388 suffer from haemophilia A and 72 haemophilia B. Twenty-five of the brother pairs are twins. The inhibitor incidence in all families with severe haemophilia A was 31.7%. The corresponding figure in the caucasian patients was 27.4%, whereas a higher incidence of inhibitors was reported in the black subjects (55.6%). Twins were reported in six of the 100 inhibitor families, for whom monozygocity was confirmed in three cases. In 32... (More)
The issue of factors predisposing for inhibitor development in haemophilia patients is still largely unresolved. In an attempt to address this problem, we initiated a registry in 1996 of siblings with haemophilia and with or without a history of inhibitors. Four hundred and sixty families have accrued, of whom 388 suffer from haemophilia A and 72 haemophilia B. Twenty-five of the brother pairs are twins. The inhibitor incidence in all families with severe haemophilia A was 31.7%. The corresponding figure in the caucasian patients was 27.4%, whereas a higher incidence of inhibitors was reported in the black subjects (55.6%). Twins were reported in six of the 100 inhibitor families, for whom monozygocity was confirmed in three cases. In 32 families (32%), at least two brothers had a history of inhibitors. In 22 (69%) of these families, the inhibitor was also of the same type, i.e. either high- or low-responding. The overall concordance within the severe haemophilia A families was found to be 78.3% (195/249) compared to an expected figure of 68.0% and 58.0% using an inhibitor incidence of 20 and 30%, respectively (P < 0.0001). The corresponding figure for the twins was 88.2% (15/17). Moreover, the risk for inhibitor development in families with a previous inhibitor history was found to be 48% (95% confidence interval [CI] 35-62%), whereas the risk in families with no previous known inhibitor was only 15% (95% CI 11-21%) corresponding to a relative risk of 3.2 (95% CI 2.1-4.9). Immune-tolerance induction was reported in 24 families, of whom 13 siblings were successfully treated. Our data clearly support the concept that a genetic predisposition for inhibitor development exists. However, the markers of this predisposition remain to be elucidated and we believe that the MIBS registry will be useful for this purpose. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
inhibitors, genetics, haemophilia, siblings, twins
in
Haemophilia
volume
7
issue
3
pages
267 - 272
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • pmid:11380630
  • scopus:6644227418
ISSN
1351-8216
DOI
language
English
LU publication?
yes
id
c1521301-8f5b-4c10-9569-5051aac7deff (old id 1120918)
date added to LUP
2008-06-24 11:45:57
date last changed
2018-05-29 09:51:45
@article{c1521301-8f5b-4c10-9569-5051aac7deff,
  abstract     = {The issue of factors predisposing for inhibitor development in haemophilia patients is still largely unresolved. In an attempt to address this problem, we initiated a registry in 1996 of siblings with haemophilia and with or without a history of inhibitors. Four hundred and sixty families have accrued, of whom 388 suffer from haemophilia A and 72 haemophilia B. Twenty-five of the brother pairs are twins. The inhibitor incidence in all families with severe haemophilia A was 31.7%. The corresponding figure in the caucasian patients was 27.4%, whereas a higher incidence of inhibitors was reported in the black subjects (55.6%). Twins were reported in six of the 100 inhibitor families, for whom monozygocity was confirmed in three cases. In 32 families (32%), at least two brothers had a history of inhibitors. In 22 (69%) of these families, the inhibitor was also of the same type, i.e. either high- or low-responding. The overall concordance within the severe haemophilia A families was found to be 78.3% (195/249) compared to an expected figure of 68.0% and 58.0% using an inhibitor incidence of 20 and 30%, respectively (P &lt; 0.0001). The corresponding figure for the twins was 88.2% (15/17). Moreover, the risk for inhibitor development in families with a previous inhibitor history was found to be 48% (95% confidence interval [CI] 35-62%), whereas the risk in families with no previous known inhibitor was only 15% (95% CI 11-21%) corresponding to a relative risk of 3.2 (95% CI 2.1-4.9). Immune-tolerance induction was reported in 24 families, of whom 13 siblings were successfully treated. Our data clearly support the concept that a genetic predisposition for inhibitor development exists. However, the markers of this predisposition remain to be elucidated and we believe that the MIBS registry will be useful for this purpose.},
  author       = {Astermark, Jan and Berntorp, Erik and White, G C and Kroner, B L},
  issn         = {1351-8216},
  keyword      = {inhibitors,genetics,haemophilia,siblings,twins},
  language     = {eng},
  number       = {3},
  pages        = {267--272},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Haemophilia},
  title        = {The Malmo International Brother Study (MIBS): further support for genetic predisposition to inhibitor development in hemophilia patients},
  url          = {http://dx.doi.org/},
  volume       = {7},
  year         = {2001},
}