INHIBITOR RISKS IN ARGENTINE PATIENTS WITH SEVERE HA. F8 GENOTYPE, STATUS CONCORDANCE IN SIBLING PAIRS AND IMMUNE GENE POLYMORPHISMS STUDIES.

MARCHIONE VD; RADIC CP; ABELLEYRO MM; PRIMIANI L; NEME D; DE TEZANOS PINTO M; DE BRASI CD; ROSSETTI LC

Orlando

Congreso; XXXII International Congress of the World Federation of Hemophilia; 2016

Federación Mundial de la Hemofilia (WFH)

Haemophilia A (HA) is an X-chromosome inherited disorder associated with deleterious mutations in the coagulation factor VIII gene (F8). The development of inhibitory antibodies is a serious complication that occurs in 15-30% of patients with severe HA in response to replacement therapy with FVIII, and affects about 20% of Argentine cases with severe HA. As a multifactorial complex trait, both genetics and non-genetics factors have been implicated in inhibitor formation (Astermark, 2006). Among patient?s genetics, the type and location of the haemophilia causative mutation have been considered as the most important factor for inhibitor development (Oldenburg et al, 2002), as well as other genetic factors such as family history and polymorphisms associated with interleukin-10 (IL10), tumour necrosis factor-ά (TNFA) and cytotoxic T-lymphocyte antigen-4 (CTLA4) genes.This study involved the analysis of severe HA patients with and without inhibitors countrywide, and it is aimed to characterise the most relevant genetic factors associated with inhibitor formation described internationally so far, including the F8 genotype and polymorphisms associated with immune genes in Argentinean patients with severe HA. OBJECTIVES Stratified our locally specific risks for inhibitor development associated with the F8 genotype in severe HA patients. Study the association of concordance/discordance status between siblings vs random pairs in patients with intron 22 inversions. Explore the influence of SNPs in IL10, TNFA and CTLA4 on the risk of inhibitor development in Argentina.