PROSPECTIVE STUDY OF THE IMMUNOLOGICAL MECHANISMS OF IMMUNE TOLERANCE INDUCTION IN HAEMOPHILIA A PATIENTS WITH INHIBITORS

Immune tolerance induction (ITI) by prolonged administration of FVIII is currently the only strategy proven to eradicate FVIII inhibitors. Long-term FVIII-specific tolerance via ITI has been suggested to be the result of a complex process that impacts on several components of the adaptive immune response, including antigen presentation, T-cell differentiation and B-cell activation and proliferation. However, the mechanisms underlying successful ITI are unclear, and not much is known about the major determinants of success vs failure. This study aims at: a) establishing a network of laboratories within the AICE Hemophilia Centers able to perform the procedures required for a prospective, in-depth immunological analysis of PBMCs; b) understanding the process of activation and immune regulation in response to FVIII in patients undergoing ITI; c) describing candidate biomarkers of ITI success or failure; d) providing the groundwork for developing a focused and strategic method of modulating the immune system during ITI.