F8 gene analysis / Immunogenotyping / HLA genotyping
J. Oldenburg and A. Pavlova will investigate the impact of genetic risk factors (gene defect responsible for haemophilia and several immune response genes) on the course and outcome of ITI.
Host genetic factors as the F8 gene defect or polymorphism of the immune response genes might act as predictors of the ITI outcome.
For this analysis DNA will be extracted from EDTA blood in the laboratory of J. Oldenburg in Bonn. The following genetic factors will be investigated:
- F8 gene
- HLA class II (DRB1 and DQB) polymorphism
- Twelve different single nucleotide polymorphisms in genes involved in the immune response, including IL-10, TNF-α, HO-1 (Hemeoxygenase-1) and CTLA-4.
- Oldenburg J et al. Risk factors for inhibitor development in haemophilia A. Haematologica 2000; 85(s10): 7-13, discussion 13-4.
- Astermark J et al. The Malmö International Brother Study (MIBS). Genetic defects and inhibitor development in siblings with severe haemophilia A. Haematologica 2005; 90: 924–31.
- Oldenburg J and Pavlova A. Genetic risk factors for inhibitors to factors VIII and IX. Haemophilia 2006; 12(s6): 15-22.
- Coppola A et al. Factor VIII gene (F8) mutations as predictors of outcome in immune tolerance induction of haemophilia A patients with highresponding inhibitors. J Thromb Haemost 2009; 7: 1809-15.
- Pavlova A et al. Impact of polymorphisms of the major histocompatibility complex class II, interleukin-10, tumor necrosis factor-α and cytotoxic T-lymphocyte antigen-4 genes on inhibitor development in severe Haemophilia A. J Thromb Haemost 2009; 7: 2006-15.
- Astermark J et al. The polygenic nature of inhibitors in haemophilia A: results from the haemophilia Inhibitor Genetics Study (HIGS) Combined Cohort. Blood 2013; 121(8): 1446-54.