The Malmö International Brother Study (MIBS): further support for genetic predisposition to inhibitor development
Version of Record online: 21 DEC 2001
Volume 7, Issue 3, pages 267–272, May 2001
How to Cite
Astermark, J. , Berntorp, E. , White, G. C. , Kroner, B. L. and THE MIBS STUDY GROUP (2001), The Malmö International Brother Study (MIBS): further support for genetic predisposition to inhibitor development. Haemophilia, 7: 267–272. doi: 10.1046/j.1365-2516.2001.00510.x
- Issue online: 21 DEC 2001
- Version of Record online: 21 DEC 2001
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.