Temple Project 1: Genetic characterization of factor VIII Inhibitors and glydosylation patterns

Temple Univ Of The Commonwealth, Philadelphia PA

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Abstract

Summary Approximately one in 5000 males in human population suffers from coagulation disorder, hemophilia A. Current treatment of hemophilia A by intravenous infusion of factor VIII concentrates is not only costly but also has a potential side effect of developing inhibitors. However, it remain unclear why such inhibitors would occur in approxiamtely 30% hemophilia A patients in which factor VIII treatment is no longer effective. Since factor VIII and its associated proteins are all glycoproteins and previous studies have suggested glycosylation of the host cells and factor VIII protein itself may have affected inhibitor formation. In this study, we have teamed up with glycobiololgy and immunology experts to dissect the mechanism of factor VIII inhibitors and glycosylation. Hence, the specific aims for this proposal are: Aim 1: To investigate the global effects of glycoforms/glycopeptides on FVIII inhibitor development; Aim 2: To investigate the role of host glycosylation genetic environment on FVIII inhibitor formation; Aim 3. To investigate tissue specific FVIII glycosylation and inhibitor formation. The success of this proposal may lead to future development of better treatment for hemophilia A patient and avoid inhibitor formation.