Immune thrombocytopenia (ITP) is a common bleeding disease caused by autoantibody-mediated
accelerated platelet clearance and impaired thrombopoiesis.
Accumulating evidence suggests that desialylation affects platelet life span in ITP.
Herein, we report on novel effector functions of autoantibodies from ITP patients
which might interfere with the clinical picture of the disease. Data from our study
show that in ITP a subgroup of autoantibodies is able to cleave sialic acid from the
surface of human platelets as well as megakaryocytes.
Autoantibody-mediated receptor desialylation interferes with the interaction between
cells and extracellular matrix proteins leading to impaired platelet adhesion and
megakaryocyte differentiation. Using a combination of ex vivo model of thrombopoiesis,
a humanized animal model, and a clinical cohort study, we demonstrate that cleavage
of sialic acid induces significant impairment in production, survival as well as function
of human platelets.
These novel findings suggest that prevention of desialylation could be a potential
therapeutic approach to treat bleeding and to improve thrombopoiesis in ITP.
