Malmö International Brother Study (MIBS): An International Survey of Brother Pairs with Haemophilia

Abstract

Malmö International Brother Study (MIBS) was initiated in 1996 in order to set up an international registry of twins and non–twin brothers with haemophilia and to search for genetic and compound factors predisposing for inhibitor development. As of July, 1997, 178 brother pairs are registered (143 haemophilia A and 35 haemophilia B patients). Sixteen of these pairs are twins. In 48 of the brother pairs (27%) there is a history of inhibitors, in 25 of them involving only one of the brothers. Immune tolerance induction has been attempted in 13 brother pairs (27%) and in four pairs the inhibitor has been eradicated. Additional demographic data need to be collected and, if possible plasma, IgG and DNA samples will be taken from inhibitor patients to serve as a tool for basic inhibitor experiments.

HLA‐DR‐restricted T‐cell responses to factor VIII epitopes in a mild haemophilia A family with missense substitution A2201P

“…Sibling studies are valuable in attempting to discern genetic factors that may predispose some individuals to developing FVIII inhibitors. The Malmö International Brother Study (MIBS) [50][51][52] has identified polymorphisms associated with inhibitor development in the IL10 [53], TNFA [54] and CTLA4 [55] genes. These risk factors are currently under investigation for the subjects of the present study.…”

Inhibitors: resolving diagnostic and therapeutic dilemmas

“…Furthermore, 50% of the current entries into the FIX inhibitors with allergic phenotype database express such mutations (I. Warrier, August 2001). However, despite these intriguing associations, several brother‐pair studies have reported that although inhibitor concordance among affected members of haemophilia A inhibitor families is greater than statistically expected, inhibitor discordance occurs [27]. Genotype, therefore, is not a sufficient determinant of inhibitor risk.…”

Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A

“…Several risk factors for the development of inhibitors to factor VIII have been identified in patients with hemophilia A. The incidence of inhibitors depends on both genetic factors (severity of hemophilia, type of mutation, 4 ethnicity, 5 family history of inhibitors, 6 the HLA genotype 7,8 ) and nongenetic factors (age at first treatment, 9,10 intensity of treatment, 11 continuous infusion, 12 and multiple product switches 13 ). The influence of the type of FVIII concentrate in PUPs with severe hemophilia A is highly controversial.…”