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Existing data support the concept that a genetic predisposition for inhibitor development exists. The aim of the Malmö International Brother Study (MIBS) is to evaluate genetic factors associated with the development of inhibitory antibodies in patients with hemophilia.
Inhibitory antibodies to factor VIII develop in 10-15% of all patients with hemophilia A and in 25-30% of patients with the severe form of the disease after exposure to factor VIII concentrates. Both genetic and environmental risk factors for inhibitor development have been evaluated, but in most cases without consistent results. Among the genetic factors, an association between large rearrangements of the factor VIII and IX genes and a higher risk for inhibitors has been described. However, a majority of patients with null mutations, including the intron 22 inversion, do not develop inhibitory antibodies. It is obvious that other genetic markers influencing the immune response to replacement therapy in patients with hemophilia remain to be identified and the aim of Malmö International Brother Study (MIBS) is to characterize these factors.
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Inclusion Criteria:
-Mild, moderate or severe hemophilia A or B and one or more brothers with mild, moderate or severe hemophilia A or B
Exclusion Criteria:
-Absence of sufficient information to classify inhibitor status
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| Name | Affiliation | Role |
|---|---|---|
| Jan Astermark, M.D., Ph.D. | Skane University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Malmö University Hospital | Malmö | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15996930 | Background | Astermark J, Oldenburg J, Escobar M, White GC 2nd, Berntorp E; Malmo International Brother Study study group. The Malmo International Brother Study (MIBS). Genetic defects and inhibitor development in siblings with severe hemophilia A. Haematologica. 2005 Jul;90(7):924-31. | |
| 11380630 | Background | Astermark J, Berntorp E, White GC, Kroner BL; MIBS Study Group. The Malmo International Brother Study (MIBS): further support for genetic predisposition to inhibitor development in hemophilia patients. Haemophilia. 2001 May;7(3):267-72. doi: 10.1046/j.1365-2516.2001.00510.x. |
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| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| 10529695 | Background | Astermark J, Berntorp E. Malmo International Brother Study (MIBS): an international survey of brother pairs with haemophilia. Vox Sang. 1999;77 Suppl 1:80-2. doi: 10.1159/000056723. |
| 23223434 | Derived | Astermark J, Donfield SM, Gomperts ED, Schwarz J, Menius ED, Pavlova A, Oldenburg J, Kessing B, DiMichele DM, Shapiro AD, Winkler CA, Berntorp E; Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort. The polygenic nature of inhibitors in hemophilia A: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort. Blood. 2013 Feb 21;121(8):1446-54. doi: 10.1182/blood-2012-06-434803. Epub 2012 Dec 6. |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |