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CELSA 2018

In collaboration with KU Leuven

Summary of the project:

 

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening microangiopathic disease caused by a severe deficiency in the plasma metalloprotease ADAMTS13 (A Disintegrin and Metalloprotease with Thrombospondin Type 1 repeats, member 13). Hyperactive ultra-large von Willebrand factor (UL-VWF) multimers in circulation cannot be cleaved when this metalloprotease is absent or dysfunctional. Consequently, microthrombi are formed by spontaneous binding of UL-VWF multimers to platelets, depriving organs from oxygen supply. Ninety-five % of the patients develop anti-ADAMTS13 autoantibodies (immune mediated TTP, iTTP) that inactivate or clear the blood protease ADAMTS13 [3]. The immune response in iTTP patients is polyclonal with an immunodominant epitope in the ADAMTS13 spacer domain. The exact mechanism how anti-ADAMTS13 autoantibodies induce ADAMTS13 deficiency is unknown. Unravelling the exact mechanism is, however, an unmet need to allow development of a targeted therapy in iTTP patients.

In the current project aims at further unraveling how anti-ADAMTS13 autoantibodies induce ADAMTS13 deficiency and at developing a targeted therapy.